13 Contact Hours
Learning objectives
Describe the epidemiology of thyroid diseases Describe pharmacologic treatment options for thyroid
Define the etiology and pathophysiology of thyroid diseases diseases (i.e. levothyroxine, radioactive iodine,
Recognize the most common signs and symptoms of propylthiouracil, etc.)
subclinical thyroid disease versus symptomatic thyroid Describe pharmacological and non-pharmacologic treatment
diseases approaches to pregnant patients
Distinguish between hyperthyroidism and hypothyroidism Describe the effectiveness of monitoring disease
Characterize the signs and symptoms present in the progression of thyroid diseases
progression of thyroid diseases Develop optimal treatment plans for individual patients with
Identify and describe the effectiveness of the diagnostic thyroid diseases based on symptomology and severity of
tests and criteria used to diagnose thyroid diseases disease
Identify neurological manifestations of thyroid diseases Describe new advancements in treatment options and early
Evaluate the various non-surgical treatment options of detection of thyroid disorders
thyroid diseases Differentiate between benign and metastatic thyroid nodules
Discuss various lifestyle modifications for patients with Design methods for educating patients on the regimens that
uncomplicated thyroid disease improve patient compliance and prognostic outcomes.
Needs assessment information
Thyroid disorders commonly affect women and geriatric well-established principles, under- and overtreatment remain
patients. The resulting complications from undiagnosed common. Physicians and other healthcare professionals can
and untreated forms of thyroid diseases are implicated in exert dramatic difference in treatment success by involving the
pregnancy fatalities, cardiovascular complications and patient personally in the treatment choices, instead of being
metabolic syndrome. The fundamental approach to the regarded merely as passive recipients of therapy. Moreover,
prevention, diagnosis, pharmacologic and non-pharmacologic they are well positioned to correct therapeutic shortcomings by
treatment of patients with various forms of thyroid diseases identifying and managing common factors that affect patient
is constantly evolving. Early detection and treatment equates compliance to therapy and monitoring, effects of common
to better patient outcomes and overall prognosis. Effective comorbid conditions, surgery, and concomitant medications and
management encompasses patient awareness and education, in the process improve overall therapeutic outcome and quality
promotion of lifestyle modifications, treatment adherence and of life.
constant monitoring of the disease progression. Despite these
Introduction
Two of the most common thyroid diseases were named after caustics and surgery. It was also around this era that Gaius
their discoverers, Graves and Hashimoto. The historical Plinius incorrectly linked goiter with the consumption of dirty
background of the thyroid gland provides the foundation drinking water, referring to the epidemics of goiter in the Alps,
necessary to understand areas of modern endocrinology such as and also suggested burnt seaweed as treatment (1).
hormone replacement therapy, feedback mechanisms, and the
use of radioactive isotopes. During the Greco-Roman period, another prominent scientist,
Gallen, incorrectly proposed the function of the thyroid gland
Goiter, or an enlarged thyroid gland, was already recognized as a secretory lubricating organ for the larynx. Just like the
as a medical problem long before the discovery of the organ Chinese thousands of years before him, he referred to burnt
involved. Its visible protrusion at the neck was a subject of sponge as treatment for goiter.
many ancient medical reports. In fact, historical records show
that as early as 1600 BC, the Chinese were already treating In 1656, the word “thyroid”, meaning shield, was given to the
goiter with burnt seaweeds. In 15 AD, a scientist named small gland on the neck by Thomas Wharton who likened its
Aurelius Celsus was among the first ancient scientists who shape to those of ancient Greek shields. The belief that dirty
clearly described thyroid tumor overgrowths, and provided drinking water caused goiter persisted for a long time, through
recommendations as to its treatment including the use of to the Renaissance period, until the discovery of iodine in
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the burnt seaweed at the start of the 19th century in Paris. understanding of the disease, most notably the link between
Its discoverer, Bernard Courtois oxidized kelp using sulfuric palpitations, exophthalmoses and the enlarged thyroid gland. In
acid to obtain the substance, iodine, meaning “violet”. Its 1909, E.T. Kocher was awarded the Nobel Prize for his work
discovery led to its universal adoption as a treatment agent for on the thyroid gland, most notably for introducing its surgical
goiter. The years succeeding its discovery made way for better removal, a technique now known as thyroidectomy (1).
Definition of terms
Thyroid gland – it is an endocrine gland that is anatomically not necessarily mean that the thyroid gland is malfunctioning. A
situated in the lower front of the neck. Its main function is goiter can occur in a gland that is producing too much hormone
to make thyroid hormones, which are secreted into the blood (hyperthyroidism), too little hormone (hypothyroidism), or the
and then carried to every tissue in the body. Thyroid hormone correct amount of hormone (euthyroidism). A goiter indicates
helps the body use energy, stay warm and keep the brain, the presence of a condition that is causing the thyroid to grow
heart, muscles, and other organs working as they should abnormally (221).
(221). The gland varies from an H to a U shape and is formed
by 2 elongated lateral lobes with superior and inferior poles Hyperthyroidism – it is a set of disorders that involve excess
connected by a median isthmus, with an average height of synthesis and secretion of thyroid hormones by the thyroid
12-15 mm, overlying the second to fourth tracheal rings. The gland, which leads to the hypermetabolic condition of
isthmus is encountered during routine tracheotomy and must be thyrotoxicosis. The most common forms of hyperthyroidism
retracted (superiorly or inferiorly) or divided. Occasionally, the include diffuse toxic goiter (Graves disease), toxic multinodular
isthmus is absent, and the gland exists as 2 distinct lobes (220). goiter (Plummer disease), and toxic adenoma (222).
Goiter – it refers to the abnormal enlargement of the thyroid Hypothyroidism – it is a common endocrine disorder resulting
gland. It is important to know that the presence of a goiter does from the deficiency of thyroid hormones (223).
Epidemiology
As of 2009, an estimated 1 percent of the American population who receive inadequate iodine in their diets. Those few who
has been diagnosed with hyperthyroidism (2). The majority of are diagnosed with hypothyroidism usually have Hashimoto’s
those diagnosed are adult women, with 12.6 million reported thyroiditis, an autoimmune disease, although it is worth noting
to have received treatment in 2008 (latest data). According to that not all patients diagnosed with Hashimoto’s thyroiditis
the Household Component of the Medical Expenditure Panel develop hypothyroidism. Pregnant women with hypothyroidism
Survey (MEPS-HC), about 23 percent of women over the age are at greater risk for developing preeclampsia, delivering
of 65 received treatment for thyroid disease, a significantly high preterm and losing the baby to miscarriage. Secondary and
percentage compared to women between 18-44 and 45-64 years tertiary hypothyroidisms are rare and estimated to occur in 1
of age (3.5 percent and 13.3 percent, respectively). According out of 80,000 individuals.
to the same survey, 12.9 percent of Caucasian non-Hispanic
women received treatment in 2008, while their Hispanic and Some of the most prevalent and leading life-threatening
black counterparts only accounted for 6.2 percent and 5.1 diseases can be caused by undiagnosed and untreated thyroid
percent of the overall treatment rate, respectively. In terms of disease. In the US and other developed countries, obesity,
healthcare costs, a total of $4.3 billion was spent on various cardiovascular disease and diabetes are leading causes of death
treatments for thyroid diseases with emergency department and all three are potentially precipitated by thyroid diseases (5).
visits and prescription medications accounting for $2.2 billion Thyroid disorders upset the hormonal regulation of metabolic
and $1.4 billion of it, respectively. The average American processes, resulting in obesity, diabetes and eventually heart
woman with thyroid disease spent $409 yearly in treatments diseases.
(3).
Thyroid disorders generally occur because of two
In the US, Graves disease or diffuse toxic goiter is the most abnormalities; dysfunction and abnormal growth of the thyroid
commonly diagnosed hyperthyroidism followed by Plummer’s gland. Benign nodules are a fairly common serendipitous
disease and toxic adenoma. Graves disease accounted for finding during routine check ups. Sometimes, during physical
60-80 percent of the diagnosed cases while 15-20 percent exams, benign nodules are noted and generally do not pose a
and 3-5 percent accounted for Plummer’s disease and toxic serious health concern because the gland’s functional integrity
adenoma, respectively. Plummer’s disease is less prevalent remains intact. Patients with benign nodule growths typically
because of the sufficient iodine found in the American diet. complain of difficulty swallowing and speaking. Thyroid
However, Plummer’s disease is the most common cause of cancers, on the other hand, are rare and can pose serious
hyperthyroidism in elderly individuals and in areas of endemic health problems. They represent approximately 1 percent of
iodine deficiency (4). new cancer diagnoses each year. Like other forms of thyroid
diseases, thyroid cancers are most prevalent in women,
Approximately 4.6 percent of the U.S. population over the especially those over the age of forty. The full recovery rate of
age of 12 years has primary hypothyroidism (2). This figure thyroid cancer with proper treatment is 90 percent (6).
is significantly lower than compared to the rest of the world
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The role of HPT Axis and hormones
In order to understand the etiology of thyroid diseases, a sound feedback loop mechanism, thus establishing a balance or “set
understanding of the hypothalamic pituitary-thyroid (HPT) axis point” that is under tight endocrinological control. For example,
or thyroid homeostasis is crucial. when circulating T3 and T4 levels decrease, the pituitary gland
increases the production of TSH and if the vice versa happens
HPT regulates the serum level of thyroid hormones, i.e. T3 and T4 levels increase in the blood, the production of
triiodothyronine (T3) and thyroxine (T4), in the serum through TSH is inhibited. Drugs, radiation, cancers, stress and other
a feedback mechanism involving several hormones and factors can upset this balance and lead to either hypothyroidism
endocrine organs. The loop begins in the hypothalamus where or hyperthyroidism.
the hypothalamic TSH-releasing hormone (TRH) is secreted,
then transported to the endocrine cells of the pituitary gland. Ultra-short feedback control also plays a role in thyroid
These cells produce thyroid stimulating hormone (TSH) hormone regulation. It is a feedback control mechanism within
which when bound to TRH receptors, stimulates the genetic the greater HPT axis negative feedback loop that regulates
expression of TSH β-subunits. When TSH matures, it is the release of thyroid hormones via auto-inhibitory actions of
released from the pituitary gland to the thyroid gland, where it TSH in its own secretion without the intermediate actions of an
stimulates the production and release of T3 and T4 (7). In turn, additional hormone.
these two hormones inhibit TRH production through a negative
Role of hormones
The synthesis and secretion of TRH is mediated by the TRH ●● T3 has 10 times higher binding specificity to receptors
gene, located on chromosome 3, in the hypothalamus and compared to T4
other endocrine organs such as the brain, pancreatic β-cells, ●● There are four times more T3 receptors than that of T4
thyrotropic C-cells, myocardium, prostate, testis, spinal cord,
epidermal layers and the anterior pituitary gland. An adequate supply of iodine is needed to maintain normal
thyroid hormone production. The daily recommended minimum
TSH consists of α and β subunits with the former located on intake is 150 mcg, with intake of less than 50 mcg frequently
chromosome 6 and the latter gene on chromosome 1. It is linked to the development of goiter. On the other hand, elevated
synthesized and secreted by the thyrotrophs of the anterior iodine levels inhibit iodide oxidation and organification;
pituitary gland. The β subunits determine the biologic excess iodine inhibits thyroglobulin proteolysis, the principal
specificity, an important function that allows for the binding mechanism for the anti-thyroid effect of inorganic iodine in
of TRH with its receptor on the thyrotrophs. Once bound, patients with thyrotoxicosis.
TSH undergoes glycosylation to become a biologically
active molecule that permits its own rapid clearance from the The physiological effects of thyroid hormones are mediated
circulation. Mutations in the TSH β gene have been implicated by nuclear receptors through gene expression regulation.
in familial central hypothyroidism. Thyroid hormones regulate metabolism, brain function and
development, respiratory, nervous and cardiovascular systems,
Thyroid hormone receptors are found in almost all body tissues. homeostasis, muscle strength, skin dryness, menstrual cycles,
T3 is the active form of the two thyroid hormones and directly weight, and cholesterol levels. Their physiological roles are
affects body tissues upon release from the thyroid gland. The discussed in detail below:
pro-hormone T4 undergoes de-iodination in the peripheral ●● Brain development and skeletal maturation of the fetus are
tissues to become T3. Thyroid hormones need to be bound with dependent on both the fetal and maternal thyroid hormone
carrier proteins such as the thyroid hormone binding globulin production. Insufficient thyroid hormones can very well
(TBG) so they can be transported. TBG binds with 75 percent lead to mental retardation and dwarfism.
and 100 percent of the circulating T4 and T3, respectively. The ●● T3 controls basal metabolism by regulating oxygen
remaining 25 percent of the circulating T4 binds with thyroxine expenditure and heat production. Abnormal T3 serum
binding pre-albumin and albumin. levels results in increased sensitivity to heat and cold in
hyperthyroidism and hypothyroidism, respectively.
In the past, T4 was considered as the main thyroid hormone. ●● T3 exerts several effects on the muscles. It is responsible for
However, recent studies have shown that T3 is actually the the stimulation and inhibition of the genetic transcription
primary thyroid hormone, because (79): of myosin heavy chain alpha and myosin heavy chain
●● T3 is physiologically four times more active than T4 beta, respectively, thereby, regulating cardiac muscle
●● T4 is convertible to T3 in the target cells contractility. Additionally, T3 stimulates the transcription
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of calcium ATPase, alters isoforms of sodium-potassium ●● Thyroid hormones stimulate bone turnover leading to
ATPase genes, and increases beta-adrenergic receptors and osteopenia in long-standing hyperthyroid condition.
G proteins levels, exerting an overall positive inotropic and ●● Thyroid hormones stimulate hepatic metabolic processes
chronotropic effects on the heart. such as gluconeogenesis and glycogenolysis resulting in
●● Thyroid hormones sensitize the tissues to catecholamine hyperglycemia in patients with hyperthyroidism.
stimulation in hyperthyroid states. This is why beta blockers ●● Thyroid hormones stimulate cholesterol production and
are a mainstay in patients with hyperthyroidism who present degradation resulting in high serum cholesterol levels in
with tachycardia and arrhythmias. patients with hyperthyroidism.
●● Thyroid hormones stimulate the GI tract leading to diarrhea
in hyperthyroid states and constipation in hypothyroidism.
Postpartum thyroiditis
Some women who have just given birth are at risk of thyroiditis. It is estimated that up to 10 percent of postpartum
developing hypothyroidism in the form of postpartum women may develop the condition within one year of delivery.
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The risk is compounded in women with comorbid juvenile short course treatment with L-thyroxine (T4) may sometimes
diabetes mellitus. be needed. Women diagnosed with postpartum thyroiditis
(anti-TPO–positive) are more likely to develop permanent
The condition is usually transient, lasting anywhere from two hypothyroidism or recurrence of postpartum thyroiditis with
to four months after delivery, and resolves by itself, though future pregnancies (10).
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although it has been observed that patients with these genes Aside from Hashimoto’s thyroiditis, other autoimmune diseases
have a clinically normal thyroid condition and function despite such as polyendocrinopathy types I and II are also associated
the increased TSH levels and normal thyroid hormone levels with hypothyroidism. These two autoimmune disorders are
in the blood. Additionally, mutations in the PAX8 gene are caused by the genetic mutation of the AIRE gene. Patients
attributed to the underdevelopment or completely absent with polyendocrinopathy type I usually presents with Addison
thyroid gland. Another disease caused by a genetic mutation disease, hypoparathyroidism, and mucocutaneous candidiasis.
that leads to hypothyroidism is Pendred syndrome. The genetic These patients are also more likely to develop autoimmune
disorder that causes hearing loss and goiter in children is thyroiditis and hypothyroidism. On the other hand, patients
linked to a mutation in the SLC26A4 gene, which results in the with polyendocrinopathy type 2 often present with adrenal
defective organification of iodine (19). insufficiency and hypothyroidism (8).
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Another genetic mutation, this time in the TRHR gene, causes large posterior fontanels, macroglossia, distended abdomen
pituitary resistance to TRH. It is an autosomal recessive with umbilical hernia, and hypotonia. Additionally, there is no
disorder with no obvious symptoms at birth. Patients with this apparent goiter. Perhaps the two most obvious signs are the
gene exhibit hypothyroidism accompanied by insensitivity to slow growth and overall developmental delay of these infants
thyrotropin secretion. The clinical signs and symptoms are (25).
often subtle and often do not develop until infants reach several
months of age. When they do appear, the first signs include A mutation in the TRH gene causes TRH deficiency. A recorded
reduced activity and increased sleep, feeding difficulties and case of a girl with congenital TRH deficiency showed positive
GIT problems, prolonged jaundice, myxedematous facies, outcomes with oral TRH therapy (26).
Genetic mutations
Just like hypothyroidism, genetic mutations are also implicated risk of developing congenital thyrotoxicosis because of the
in the development of hyperthyroidism. For example, McCune- transplacental passage of maternal antibodies that stimulate the
Albright syndrome, caused by GNAS mutations, causes a thyroid gland. The condition is self-limiting because the infant
variety of endocrine dysfunctions such as hyperthyroidism, can clear the maternal antibodies from its circulation in 12-16
precocious puberty, Cushing’s syndrome, and acromegaly (27). weeks after birth. In severe forms of the disease, there may
be fetal death, although this is very unlikely. Upon physical
There are several other genetic disorders that cause TSH examination, the infants may exhibit rapid pulse, heart failure,
receptor gene mutations, leading to hyperthyroidism, namely; and severe weight loss with failure to thrive. Goiter rarely
●● Familial gestational hyperthyroidism develops (30). Toxic thyroid adenoma due to somatic mutations
●● Transient nonautoimmune hyperthyroidism in the TSH receptor is exceptionally rare.
●● Congenital nongoiterous thyrotoxicosis
●● Toxic thyroid adenoma with somatic mutation Type II autoimmune polyendocrine syndrome (APS-II), also
known as Schmidt’s syndrome, is the most common form of
Studies have found that women who developed familial polyglandular failure syndromes. It is a very rare autoimmune
gestational hyperthyroidism exhibited elevated serum levels disorder consisting of Addison’s disease, juvenile diabetes
of human chorionic gonadotropin hormone (hCG). Normally, mellitus and autoimmune thyroid disease (Hashimoto’s
hCG stimulation of the thyroid gland during early pregnancy thyroiditis or Graves disease). The adrenal insufficiency is a
is expected because TSH and hCG closely resemble each result of the autoimmune destruction of the adrenal cortex (31).
other’s structures, allowing their receptors to accommodate
both hormones (28). Another type of hyperthyroidism that Thyroid diseases of autoimmune origins are linked to human
occurs in the first trimester is transient nonautoimmune leukocyte antigen (HLA)-DRw3 and HLA-B89. Patients with
hyperthyroidism. As the name suggests, the condition resolves Graves disease, subacute painful or granulomatous thyroiditis
by itself. Clinically speaking, women who are diagnosed with are usually found to have HLA-related defects. Additionally,
this condition have hyperthyroidism but do not present with TSHR genes with single-nucelotide polymorphism are seen in
laboratory evidence of thyroid autoimmunity or signs and 33 percent of patients with Plummer disease (32).
symptoms consistent with Graves disease. Instead, they may
present one or many of the following clinical manifestations
(29):
●● Normal pregnancy
●● Mild nausea and vomiting
●● Hyperemesis gravidarum
●● Twin or multiple pregnancies
●● Mutation in the TSH Receptor
●● Hyperplacentosis
●● Hyperreactio luteinalis
●● Hydatidiform mole
●● Choriocarcinoma
Subacute thyroiditis
The second most common cause of hyperthyroidism is subacute thyroid hormone, rather, it results from the destructive changes
thyroiditis, accounting for approximately 15-20 percent of to the thyroid gland and subsequent inappropriate release of
diagnosed cases. Unlike Graves disease, this inflammatory preformed thyroid hormone. Patients with this disease can
thyroid disease does not result from excessive synthesis of expect hypothyroidism to follow (33).
Toxic solitary or multinodular goiter
Toxic multinodular goiter or Plummer disease is the least with their condition being serendipitously found during
common form of hyperthyroidism, accounting for only routine screening. Additionally, because of the autonomous
approximately 10-20 percent of diagnosed cases. Its incidence hyperfunctional nature of the nodules, toxic solitary and
is higher in elderly individuals with chronic goiter. It has been multinodular goiters usually do not remit (34).
proposed that gene mutations are responsible for the slow but
steady thyroid activation that occurs over time. As a result, Because of only mild elevations of thyroid hormones, the signs
elevation of thyroid hormone is slow and may only appear to and symptoms of hyperthyroidism due to toxic solitary and
be mildly elevated at the time of diagnosis. Patients with this multinodular goiters do not set off alarm bells until the patient
type of thyroid disease have none of the autoimmune clinical has already developed complications. However, when these
symptoms and lab findings such as circulating antibodies found patients are exposed to iodinated radiocontrast or administered
in patients with Graves disease. They are usually asymptomatic, amiodarone, the elevated thyroid hormone levels become more
pronounced.
Toxic adenoma
Toxic adenoma refers to the benign monoclonal nodular growth Aside from toxic adenoma and toxic solitary and multinodular
which results in autonomous hyperfunctioning of follicular goiters, other forms of benign thyroid growths will be discussed
thyroid cells. It is a very rare form of hyperthyroidism, in the succeeding pages.
accounting for only approximately 2 percent of the diagnosed
cases. The excess thyroid hormones produced inhibits TSH Other causes of hyperthyroidism are rare, namely; metastatic
production and secretion (35). thyroid cancer, struma ovarii, iodide-induced thyrotoxicosis,
and molar hydatidiform pregnancy.
Struma ovarii
Struma ovarii is a very uncommon ovarian tumor, accounting of the overall mass. It secretes excessive thyroid hormones,
only for 1 percent of all ovarian tumors. It is characterized by causing hyperthyroidism (37).
the presence of approximately fifty percent of thyroid tissue
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autoimmune thyroid disease and acts as a substrate for studies using iodine-containing contrast agents. The condition
additional thyroid hormone synthesis. most likely results from the inability of the thyroid gland to
cope with iodide excess. It is easily treated with cessation of
Iodide-induced thyrotoxicosis also occurs in patients with the excess iodine administration accompanied followed use
multinodular goiter or autonomous nodule. Iodide-induced of anti-thyroid medications. Usually, after elimination of the
thyrotoxicosis or Jod-Basedow syndrome is a frequent excess iodine from the body, normal thyroid function returns to
occurrence in patients who underwent radiologic treatment or pre-exposure levels (33).
Drug-induced hyperthyroidism
The antiarrhythmic drug amiodarone is rich in iodine and may also induce thyroiditis with hyperthyroidism and other
structurally resembles the thyroid hormone, T4, and stimulates thyroid disorders (33).
its receptors. The recombinant protein drug, interferon-alpha
hCG-induced hyperthyroidism
As discussed previously, hCG also stimulates TSH receptors. especially pronounced during the first trimester of pregnancy
Patients with a molar pregnancy, choriocarcinoma and but subsides quickly as the pregnancy progresses, usually
hyperemesis gravidarum produce extremely high levels of when the molar pregnancy is evacuated, the choriocarcinoma is
serum beta human chorionic gonadotropin (β-hCG), a weak managed, and hyperemesis gravidarum resolves by itself (33).
agonist of the TSH receptor. The elevated levels of hCG are
Malignant thyroid diseases
Malignancy is also a possible cause of hyperthyroidism, ●● anaplastic carcinomas
although it is a rare occurrence in the US. It commonly ●● primary thyroid lymphomas and,
manifests as a painless, palpable, solitary thyroid nodule. ●● primary thyroid sarcomas
Thyroid cancer may spread to the lymph nodes, lungs, bone
and sometimes brain. There are also instances where the growth These carcinomas primarily arise from the two types of cells in
is localized to the neck region, also referred to as locally the thyroid gland, namely:
advanced cancer, affecting primarily the trachea, esophagus, ●● Endodermally-derived follicular cell gives rise to papillary,
blood vessels, muscles, or nerves (36). There are several forms follicular, and probably anaplastic carcinomas.
of thyroid cancer, namely (38): ●● Neuroendocrine-derived calcitonin-producing C cell gives
●● papillary carcinomas rise to MTCs. Thyroid lymphomas arise from intrathyroid
●● follicular carcinomas lymphoid tissue, whereas sarcomas likely arise from
●● medullary thyroid carcinomas (MTCs) connective tissue in the thyroid gland.
Papillary carcinoma
Papillary carcinoma is the most common form of all thyroid association with Gardner syndrome (familial adenomatous
neoplasms. Exposure to radiation has been strongly linked to polyposis). Tumors typically appear late, about 10-20 years
increased risk for papillary thyroid carcinoma. This finding after exposure.
is backed by historical data that spans more than 50 years
of populations affected by well known nuclear explosion Papillary carcinoma is characterized by its slow-growth
and accidents, namely the Chernobyl plant accident and arising from T4 and thyroglobulin-producing follicular cells
atomic bombings of Hiroshima and Nagasaki. Additionally, of the thyroid gland. These cells take up iodine, respond to
retrospective studies have found that patients who received TSH stimulation and synthesize thyroglobulin, all of which
low-dose radiation therapy for benign tumors also developed aid in the diagnosis and treatment of residual disease and
papillary carcinoma later on in their lives. However, the same recurrences after surgical excision. Tumors can pierce through
cannot be said for patients who received low-dose radiation the thyroid capsule to invade the trachea and other surrounding
exposure from imaging studies. Also, patients who did radiation structures; invasion of the former results in hemoptysis and
therapy such as iodine-131 ablation of the thyroid did not airway obstruction. Impingement of the laryngeal nerves causes
develop papillary thyroid carcinoma presumably because hoarse, breathy voice and, sometimes, dysphagia. Involvement
cytotoxicity increases with these doses (38). of the cervical lymph nodes is very common with the central
compartment (level 6) being the most common site affected.
Aside from radiation exposure, papillary carcinoma has also
been reported as a familial disease, occurring singly or in
Follicular carcinoma
Metastatic follicular carcinoma is the second most common diagnosed cases. Populations who receive inadequate intake
form of thyroid cancer, accounting for about 10 percent of
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of dietary iodine have a high risk of developing follicular and Hürthle cell carcinoma or oncocytic carcinoma is a malignancy
anaplastic carcinomas (38). variant of follicular carcinoma, making up 2-3 percent of the
overall thyroid cancer cases. It is characterized by Hürthle cells,
The lesions produced by the rapidly growing follicles may which almost always makes up more than 75 percent of the
stimulate the thyroid gland, resulting in high levels of thyroid tumor mass. Hürthle cells are large, polygonal follicular cells
hormones, or thyrotoxicosis. Excessive production of thyroid that contain abundant granular acidophilic cytoplasm. They are
hormone happens rarely from functioning metastatic follicular found in several benign thyroid conditions, such as Hashimoto
carcinoma. thyroiditis, Graves disease, and multinodular goiter. Like other
thyroid diseases, they are more common in elderly women.
Anaplastic carcinomas
Anaplastic or undifferentiated carcinoma is one of the rarest and very late onset in life, prognosis is usually grim, with death
forms of thyroid carcinomas, accounting for only about 1.6 occurring within months of confirmed diagnosis (40).
percent of all diagnosed cases. However, it is considered the
most aggressive of all thyroid malignancies and offers one Anaplastic thyroid carcinoma presents as a rapidly growing
of the worst survival rates of all malignancies to stricken thyroid mass that is associated with local symptoms such
patients. They may be further grouped into small cell or large as hoarseness and dyspnea in about half of the patients.
cell carcinomas. Like other thyroid diseases, it mostly affects Sometimes, patients will also present with vocal cord paralysis,
women at a ratio of 3:1 for women. Patients with anaplastic and cervical metastases. Because of its rapid growth, at least
thyroid carcinomas present much later compared to other one half of patients already have distant metastases (e.g. lungs,
thyroid malignancies, usually in the sixth or seventh decade of bones and brain) at the time of diagnosis.
life. Because of its rapid progression, local invasive propensity
Primary thyroid lymphomas and primary thyroid sarcomas are
rare.
RISK FACTORS
The risk factors for certain forms of thyroid diseases have
been partially discussed already. In the succeeding pages, more
details will be discussed and explained.
Nonetheless, it seems more likely that the twin action of Alternatively, there are several studies that point to the
tobacco smoke is a result of the combined effects of the several protective effects of smoking from thyroid cancer. Results
components of smoke namely, nicotine, hydroxypyridine from a pooled analysis of 14 case–control studies gathered
metabolites and benzpyrenes, which may also interfere with from the United States, Europe and Asia point to the link
thyroid function. It is not clear whether tobacco has any between cigarette smoking and reduced risk of thyroid cancer,
effect on the actions of thyroid hormone in the peripheries. particularly papillary and follicular cancers. The study further
Additionally, smoking may also indirectly influence thyroid noted that the benefit was more pronounced in current smokers
function either through a long term and sustained sympathetic than former smokers, and illustrated the significant trends
stimulation that results in increased secretion of thyroid of reduced risk with longer duration and greater frequency
hormones or by upsetting the delicate immunological balance. of smoking. There are four proposed explanations for these
findings (41):
Some studies strongly suggest smoking to be a risk factor for ●● Firstly, the significant reduction of TSH secretion induced
Graves hyperthyroidism, with severe Graves ophthalmopathy by smoking may play a role.
(GO) among those who smoke. Smoking induces immunogenic ●● Secondly, smokers have long been associated with lower
activity by altering the thyrotropin receptor, causing the body weight compared to nonsmokers, therefore, the risk
retro-orbital tissues to be more susceptible to the antibodies. for thyroid cancer may also be likewise lower.
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●● Thirdly, smoke possesses anti-estrogenic effects. This adrenal cortex, resulting in greater release of male hormones in
hypothesis is particularly significant since thyroid cancer the adrenal gland. On the other hand, some studies have shown
has higher incidence among women, suggesting an etiology that the additive actions of nicotine to adrenocorticotropic
with estrogenic roots. hormone (ACTH) in the peripheries may lead to stimulation of
●● lastly, low levels of circulating thyroid autoantibodies adrenal steroidogenesis (41).
correspond to lower incidence of hypothyroidism.
Aside from the steroid hormones, it is also thought that
However, the role of these antibodies in the possible smoking contributes to elevated serum cortisol levels. Long
development of autoimmune hypothyroidism upon smoking term smoking is tied to elevated salivary cortisol, with
cessation should also be considered. A study by Mestman stimulation of catecholamines release as a possible mechanism.
et al. revealed a sharp but brief rise in the incidence of This finding is backed by studies that found decreased serum
hypothyroidism in both men and women of all ages upon cortisol levels in individuals who stopped smoking. The
nicotine withdrawal. The researchers concluded that the implication of the effects of smoking on cortisol levels is
incidence of clinical hypothyroidism is increased six times especially important when considering stress responses. There
more within 2 years of quitting cigarettes. These findings are two proposed mechanisms for the altered stress responses
point to the need to consider hypothyroidism as the cause brought on by nicotine, namely (41);
of untoward symptoms such as weight gain and tiredness in ●● Decreased effects of nicotine on the affinity of receptors to
patients who recently stopped smoking (43). catecholamine stimulation
●● Chronic nicotine leads to reduced sensitivity to the
Aside from thyroid hormones, it is also thought that smoking stimulating effects of ACTH, prolactin, and growth
adversely affects adrenal cortical hormone levels by decreasing hormone (GH).
the enzyme activity of either 21- or 11-beta-hydroxylase in the
Stress
The role of stress in the pathophysiology of Graves disease was mice model, with both Th1 and Th2 cells showing vital
put forward during the Boer War and World War I. Although, roles for the development of the iodine-induced autoimmune
it is hard to pinpoint the exact effects of stressful events and thyroiditis in non-obese diabetic mice (47).
the actual onset of Graves disease with retrospective analysis
of studies, the role of stress on Graves disease is nevertheless A study published recently found a strong link between the
recognized to be plausible. In the recent years, various clinical degree of stress, intensity of symptoms and the biological status
observations backed by modern advances in immunology and with the first onset of Graves disease. Participants belonging to
broader understanding of autoimmune diseases have proposed the older age group were found to exhibit hyperthyroidism of
that stress hormones disrupt the balance of T-helper cell levels lesser severity and lower fT3 and fT4 serum levels, revealing
in the body (44). the clinical effects of stress on Graves disease. Another
study on patients treated with radioactive iodine found the
Although Graves disease is thought to be a familial disease, potentiating effects of stress on autoimmunity. The results
heredity does not fully explain the pathophysiology of the showed that patients with history of stress were later on more
disease. Environmental factors are thought to be responsible for affected by hypothyroidism. Additionally, two other studies
21 percent of the diagnosed cases. The table below lists these implicated the role of stress in the delayed improvement of
factors (46). thyroid disease following anti-thyroid drug therapy (48).
Page 12 Nursing.EliteCME.com
endocrine hormones such as pituitary gonadotropin, growth a result, the reduction in dehydroepiandrosterone production
hormone and TSH. Specifically, the pathway renders the promotes Th2-type immunity. It is worth noting though that
receptors of sex hormones and growth factors resistant to dehydroepiandrosterone levels naturally decline with age so
these substances. It also suppresses 5’ deiodinase, which if dehydroepiandrosterone contributes to the development
converts the relatively inactive T4 to T3, aggravating of Graves’ disease, the highest incidence for Graves’ disease
further the suppression of reproductive, growth and thyroid would have been in the geriatric population, and not in the
functions. It promotes visceral adiposity, insulin resistance, young adult, as the case is (49).
dyslipidemia, hypertension and osteoporosis.
●● The hypothalamus stimulates the beta-endorphin pathway Aside from steroid hormones, the T and B cells also express
which represses pain perception and induces analgesia. The receptors to epinephrine and norepinephrine, and other cells of
hypothalamic-pituitary-adrenal axis and glucocorticoids the immune system, namely; natural killer cells, monocytes,
inhibit the CRH, LC/NE and beta-endorphin pathways and macrophages. They inhibit the production of IL12 by
together. antigen presenting cells (APCs), suppress the production of
TNF-α, and potentiate the production of IFN-γ by APCs.
The T and B cells express steroid hormone receptors, Receptors of Β2 cells are expressed only on Th1 cells. Their
specifically, the glucocorticoid receptors. At therapeutic doses, agonists suppress the production of IFN-γ by Th1 cells.
glucocorticoids act as immunosuppressants by disrupting Moreover, the stimulation of epinephrine–lipopolysaccharide
leukocyte migration, reducing antigen presentation and dendritic cells secretes IL12 and IL23 for IL4 and IL17
expression of MHC class II antigens, suppressing of the production by effector T-cells. The resulting Th2/Th17 setting
proliferation and differentiation of lymphocytes, and reducing is linked to many autoimmune diseases (50).
cytokine activity. However, during stressful situations,
the glucocorticoids produced by the body at endogenous Glucocorticoid and catecholamine mediated actions on the
concentrations have immunomodulation effects. They immune system are not the only pathways that are associated
inhibition the production of IL12 by antigen presenting cells with autoimmune diseases. Depression and stress stimulate
and reduce the expression of IL12 receptors on T cells. On the release of inflammatory cytokines, such as interleukin-6,
the other hand, glucocorticoids stimulate the production of dendritic cells and macrophage-produced cytokine. The
IL4 and IL10 by Th2 cells, thereby, creating an imbalance in increased interleukin-6 levels during stress causes a disruption
favor of Th2 cells which results in the development of humoral in the Th1/Th17/Treg balance. Additionally, NF-κB is also
immunity. When stressful situations occur, the adrenal gland produced after stress, which in turn stimulates NF-κB signaling
produces lesser amounts of dehydroepiandrosterone, the in mononuclear cells. The role of cytokines in regulation
hormone that controls the immunity toward a Th1 response. As mechanisms can trigger Treg stimulation and release, affecting
the development of Graves disease (51).
Pregnancy
There are two hormones that are elevated during pregnancy— Hyperthyroidism in pregnancy manifests as:
human chorionic gonadotropin (hCG) and estrogen— which ●● Poor concentration and nervousness
increases serum thyroid hormone levels. As mentioned above, ●● Tremor, heat intolerance and hyperhidrosis
hCG is secreted by the developing placenta and is structurally ●● Hyperdefecation
related to TSH, able to stimulate the thyroid to produce excess ●● Proximal muscle weakness
thyroid hormones. The elevated presence of estrogen in turn ●● Enlarged thyroid gland
results in the increased amount of thyroxine-binding globulin
in the body, making thyroid hormone transportation in the Hyperthyroidism in pregnancy manifests as:
blood easier and faster. Additionally, the thyroid gland slightly ●● Lethargy
increases in size in healthy women during pregnancy, but not ●● Weight gain
noticeable enough to be detected during a routine physical ●● Constipation
check up, a condition called subclinical hyperthyroidism. On ●● Cold intolerance
the other hand, if the gland is enlarged enough to be detected, a ●● Stiffness
strong sign of thyroid disease, it should be assessed as soon as ●● Muscle cramping
possible. The hormone level alterations, increased thyroid size ●● Carpal tunnel syndrome
and other symptoms common to both pregnancy and thyroid
disease make the latter’s diagnosis difficult (52).
Hyperthyroidism in pregnancy
The incidence of hyperthyroidism in pregnancy is largely improvement during the second and third trimesters. The
attributed to Graves disease, occurring in a ratio of 1:500 remission may be a result of the overall immune system
pregnancies (52). Although Graves disease may make its suppression occurring during pregnancy. However, the disease
initial appearance during pregnancy, a woman who is already exacerbates during the first months following delivery. Graves
diagnosed with it may actually experience symptomatic disease during pregnancy should be monitored monthly (53).
Nursing.EliteCME.com Page 13
Another condition during pregnancy that can possibly It is worth noting that women who underwent radioactive
precipitate hyperthyroidism is hyperemesis gravidarum, an iodine therapy or surgery to correct Graves disease in the
extreme case of nausea and vomiting that often results in past may still have existing TSI antibodies in the blood
weight loss and dehydration. The elevated levels of hCG is even when thyroid levels have reached normal levels. These
thought to be the triggering factor to the condition as well as the antibodies cross the placental barrier into the fetal bloodstream,
transient hyperthyroidism during the first trimester. stimulating the thyroid gland. However, if the mother is
under anti-thyroid medications, the fetus may not develop
Uncontrolled hyperthyroidism during pregnancy can affect the hyperthyroidism because these drugs also cross the placental
baby in a number of ways, namely; barrier and enter the fetal circulation.
●● It can cause congestive heart failure
●● It can cause preeclampsia Untreated hyperthyroidism in infants may result in
●● It can cause thyroid storm tachycardia, which in turn may lead to heart failure, congenital
●● It can lead to miscarriage malformations, poor weight gain, irritability, and rarely, an
●● It can lead to early labor enlarged thyroid that protrudes into the trachea, obstructing the
●● It can lead to low birth weight airway and interfering with breathing.
Hypothyroidism in pregnancy
Generally, the hypothyroidism that occurs during pregnancy in preventing exacerbation into permanent hypothyroidism
can be mainly attributed to the autoimmunedisorder, (53).
Hashimoto’sthyroiditis.
PPT proceeds in three stages:
Untreated, or undertreated, hypothyroidism may very well 1. Hyperthyroid stage: T3 and T4 release due to thyroid
lead to serious fetal and maternal risks such as pre-eclampsia, destruction
placental abnormalities, low birth weight infants, and 2. Hypothyroid stage: Lower T3 and T4 levels due to the
postpartum hemorrhage. Like subclinical hyperthyroidism, mild destroyed gland
hypothyroidism is also hard to detect because of the similarity 3. Euthyroid stage: Resolution of thyroiditis
of its symptoms with pregnancy (53).
They occur within a year after delivery and detecting it is
Postpartum thyroiditis (PPT) occurs in 4-10 percent of women. crucial since some women may get pregnant right away.
It is a variant of the chronic Hashimoto’s thyroiditis and its Symptoms vary depending on the stage of the disease at the
causes are also rooted in autoimmune mechanisms that usually time of symptomatic manifestation and diagnosis. Women who
develop during the first year following delivery. Its peak had or have current autoimmune thyroid disease should get
incidence is at 6 months. It is characterized by the presence of their thyroid antibody values assessed at the end of the first
antimicrosomal antibodies and manifests clinically as transient pregnancy. Women who tested positive for thyroid receptor–
thyrotoxicosis, hypothyroidism, or transient thyrotoxicosis stimulating antibodies or are taking anti-thyroid medications
followed by hypothyroidism. Although the manifestations may should undergo fetal ultrasound at least once a month after
not always be unrecognizable, their early detection is important twenty weeks of gestation (53).
Fetal thyroid dysfunction presents with a heart rate of more Generally, fetal and maternal health outcomes vastly improve
than 160 beats per minute, fetal goiter, hydrops and intrauterine with rapid resolution of thyroid dysfunction.
growth restriction.
Aside from the risk factors discussed above, there are other
contributing causes to thyroid diseases.
Age
Thyroid cancer
The incidence of thyroid cancer can occur at any age, though Women are usually diagnosed during midlife while men who
its risk increases earlier for women when compared to men. are diagnosed are usually already well in their 60s or 70s (54).
Page 14 Nursing.EliteCME.com
Hyperthyroidism
Like other hyperthyroid patients, bodily processes such as an elderly patient may only have one or two of those, making
metabolism tend to speed up. However, while the younger diagnosis difficult in this population group (55).
patient may often exhibit multiple symptoms of the disease,
Hypothyroidism
An increased prevalence of hypothyroidism has been distinct subset of symptoms and this is even more so in the case
consistently found in the elderly population. Although there are of elderly patients. For example, memory loss and decline of
several factors that are thought to contribute to the widespread cognitive function is often associated with the natural processes
prevalence, almost all studies report higher rates for both overt of aging but at the same time, these two may be the only
and subclinical hypothyroidism in women with advancing age. presenting symptoms of hypothyroidism. Other symptoms such
as weight gain, sleepiness, dry skin, and constipation, may also
Furthermore, the incidence ratio of undiagnosed be present but lack of these symptoms does not rule out the
hypothyroidism in nursing home residents over 60 years old is diagnosis. In order to make a confirmed diagnosis, clinicians
approximately 1:4. The risk increases with age (56). often need a high index of suspicion such as a positive family
history of thyroid disease and extensive history of radiation
Unlike symptoms of hyperthyroidism, clinical manifestations
therapy around the neck area (56).
of hypothyroidism are very broad to be classified under one
Gender
Thyroid diseases are more common among women. Several hand, an independent association of low-T3 levels with men has
epidemiological studies in adult population strongly suggest a been found in elderly patients living at home.
greater prevalence of thyroid disease in the female gender.
Advancing age is an important contributing factor to assessing
The sex-related differences in the prevalence of the aggressiveness of thyroid cancers. Both follicular and
hyperthyroidism is not clearly defined although a lot of the anaplastic variant of thyroid cancer are more prevalent in
diagnosed cases of Graves disease and toxic multinodular goiter the elderly. Epidemiological studies on the aging population
proportionally increase or decrease with dietary iodine intake. reiterate the fact that men are less affected by thyroid disease
Another factor to consider is the underlying nodularity and than women. However, elderly males may still be at risk for
functional autonomy of the thyroid gland which may become thyroid cancer, a point to remember in the evaluation of thyroid
more overt as iodine exposure increases (55). nodules among the geriatric population (55).
Like other forms of hyperthyroidism, subclinical In another note, a study by Hsieh et al. showed that men
hyperthyroidism is more common among women than men, diagnosed with papillary thyroid cancer and underwent
especially in patients more than 70 years of age. Declining T3 thyroidectomy had poorer prognosis. Specifically, males
levels is common in the elderly and because low T3 is often exhibited higher thyroid cancer mortality rates than females.
a result of other underlying diseases, it is difficult to clearly Multiple regression analysis pointed to the male gender being
identify a sex-related difference in its prevalence. On the other an independent risk factor for thyroid cancer recurrence and
death (58).
Nitrate intake
A study by Ward et al. in 2010 found an association between Specifically, the study found an increased risk of thyroid cancer
nitrate contamination and risk for thyroid disease. Nitrate with nitrate levels in the public water supply exceeding 5
contamination of food and drinking water is a potential source mg/L. However, there was no distinct link with the prevalence
of nitrate intoxication that can lead to thyroid dysfunction. of hypothyroidism or hyperthyroidism. Dietary nitrates also
Once ingested, nitrates are converted into nitrites, chemical exhibited similar effects on thyroid function. The hypothesis
substances that compete with iodide uptake by the thyroid, that nitrate-contaminated water plays a role in the etiology of
reducing the available iodine needed for normal thyroid thyroid cancer warrants further study (57).
hormone production (57).
Juvenile diabetes
According to a study by Betul et al. of Cleveland, Ohio, Thyroid diseases and juvenile diabetes are “sister diseases”, in
individuals with juvenile diabetes are more likely than others the sense that they have the same root cause – autoimmunity.
to develop autoimmune thyroid disorders. It also reiterated The antibodies for each disease are different. Additionally,
the fact that women are about 8 times more likely to develop having an autoimmune disease puts the individual at risk of
thyroid disease (59). another autoimmune disease. These diseases also have familial
Nursing.EliteCME.com Page 15
roots; an example is a grandparent with hyperthyroidism and an occurrence. Moreover, untreated thyroid conditions adversely
offspring with juvenile diabetes. affect blood sugar levels in individuals with juvenile diabetes.
Also, the unexplained weight gain associated with insulin use
The most common thyroid disorder associated with juvenile may be attributed to an underactive thyroid (59).
diabetes is Hashimoto’s thyroiditis while 10 percent of
diagnosed cases developed Graves disease. Generally, juvenile In the beginning, autoimmune thyroid disease can present as
diabetes occurs first and followed by thyroid dysfunctions at episodes of hypothyroidism followed by normal thyroid levels.
some point in the future. However, this isn’t always the case. The symptomatic episodes can happen on and off as the thyroid
Many people are first diagnosed with juvenile diabetes during is being continuously damaged by the immune system (59).
midlife, making way for the possibility of the reverse order of
Obesity
Central obesity is associated with many endocrine disorders and body mass index may be due to the leptin produced by fat
including thyroid dysfunctions. T3 regulates glucose and tissues. Leptin inversely affects thyroid hormone production
lipid metabolism and thermogenesis. Thyroid dysfunction and release, and endocrine activity in many ways. Firstly, it
is independently linked to body weight and composition plays an important physiological role in regulating energy
alterations, body temperature shift, and total and resting homeostasis (65). It works in conjunction with the central
energy outflow. Sometimes, the onset of weight gain occurs nervous system in altering neuroendocrine and behavioral
after thyroid dysfunction treatment. Results from past responses to overeating, maintaining a balance between energy
studies propose slight variations in thyroid function such as intake and expenditure. Secondly, leptin also regulates the
those in subclinical thyroid diseases to be risk factors to the hypothalamic-pituitary-thyroid (HPT) axis (65) (66) through
development of regional obesity and weight gain risk (60). TRH gene expression in the paraventricular nucleus, an action
that results in TSH-stimulated leptin release by the adipose
Furthermore, body mass index has been adversely associated tissues (66) (67) (68). Lastly, it affects thyroid deiodinase
with fT4, fat accumulation with decreased fT4 (61) (62) and activities with activation of the T4 to T3 conversion (64) (69).
elevated TSH levels with overweight but euthyroid individuals, A good example is the altered thyroid function occurring with
pointing to a positive correlation between TSH and the normal feedback regulation in subclinical hypothyroidism. It
inevitable weight gain over time (63). may be the critical event that stimulates energy expenditure
changes with resulting BMI and weight elevations.
Adipose tissues are part of the endocrine system because they
produce and release leptin (64). The relationship between TSH
Diet
Unhealthy diet with deficient nutrients plays an important role ●● Iodine
in the development of various thyroid disorders. These nutrient ●● Vitamin B12
deficiencies are listed below and discussed in detail in the ●● Selenium
succeeding pages (70): ●● Vitamin D
Iodine
Iodine deficiency has been cited as the most common cause of As mentioned previously, iodine deficiency is the most
thyroid disorder in developing countries, which ultimately leads important risk factor for goiter and it has been shown in studies
to goiter formation and hypothyroidism (71). that “characterization of iodine status of a population has a
central role in thyroid epidemiology” (74). It has also been
Iodine deficiency has been reported to be the major risk suggested that the knowledge of iodine intake level of a certain
factor for the growth and development of hypothyroidism geographical area or a particular population is very important in
in approximately 800 million people inhabiting the iodine understanding the pattern and prevalence of thyroid disorders
deficient areas of the world (72). and planning for their medical surveillance and treatment (75).
Iodine is an essential requirement that functions as the substrate Research has shown that even small fluctuations in iodine
for the synthesis of thyroid hormones. The minimum daily intake level have an impact on the prevalence of goiter,
requirement of iodine is approximately 50 micrograms. nodules, and thyroid dysfunction. A relative decrease in the
Both deficiency and excess of iodine creates an imbalance serum concentration of thyroid stimulating hormone occurs
in the thyroid hormonal regulation. When the supply of with age in the case of mild to moderate iodine deficiency.
iodine changes (e.g. excess iodine intake), an auto-regulatory
mechanism is activated to prevent further changes. This
mechanism is also referred to as Wolff–Chaikoff effect and
escape (73).
Page 16 Nursing.EliteCME.com
Iodine deficiency to the low intake of iodine. Severe iodine deficiency needs
immediate attention while less severe iodine deficiency results
Iodine deficiency has severe pathologic consequences including in multinodular autonomous growth and function of the thyroid
endemic goiter, endemic cretinism, increased fetal and infant gland which eventually leads to goiter and hyperthyroidism
mortality and enhanced prevalence of motor and neuromotor among the middle aged and elderly individuals (76).
disabilities in large populations (73). It has been reported
that the overall health status of a population is affected by Iodide oxidation to iodine is essential in thyroid hormogenesis.
developmental brain disorders and goiter resulting from A deficiency of iodine may result in oxidative stress, high
iodine deficiency and this in turn, adversely affects the overall concentration of thyroid stimulating hormone (TSH) and
performance and financial status of a population. The onset increased concentration of hydrogen peroxide which cannot
and prominence of the thyroid abnormality are directly related be used in the synthesis of thyroid hormones since the iodide
molecule is lacking (77).
Excess iodine
Excess iodine ingestion commonly results from the use of with hypothyroidism, with elderly individuals being the most
medicinal preparations of iodine or radiographic contrast media. likely affected (76).
It can especially lead to serious pathologic consequences in
cases where thyroid auto-regulation is defective or absent Additionally, excess iodine exerts a cytotoxic effect on the
such as fetal and neonatal thyroid Hashimoto’s thyroiditis. thyroid cells as a result of formation of free radicals. Necrotic
Multinodular goiter may result from defective thyroid auto- and apoptotic mechanisms with necrosis are believed to be at
regulation mechanism and an excess of iodine in this situation play in the development of goiter and apoptosis during iodide-
can result in thyrotoxicosis or Jod-Basedow disease (73). induced thyroid involution (77).
Many studies have shown that severely excessive intake of It has been reported that the pathologic manifestation of iodine
iodine is associated with a hypofunctional thyroid and goiter in excess can be readily eliminated when the source of iodine is
children. A moderate to mild excess of iodine are associated removed (73).
Goitrogenic foods
Goitrogens are naturally occurring substances which interfere Other goitrogenic foods include peaches, strawberries, peanuts,
with the normal functioning of the thyroid gland. Such radishes, spinach and millets. In euthyroid populations, there is
substances have the ability to enhance the size of the thyroid to no evidence suggesting any adverse role played by goitrogenic
compensate in cases where there is low production of thyroid foods in thyroid function. Rutabaga and turnip contain goitrin,
hormones. an anti-thyroid compound. Goitrin is thought to be derived from
progoitrin through enzymatic hydrolysis by the action of an
Foods containing goitrogens are classified in two classes: enzyme called thioglycosidase that is found in the plant itself
●● Soy and soybean related foods (87). Goitrogens have also been reported to be present in the
●● Cruciferous vegetables red outer skin of certain edible nuts such as peanuts and ground
nuts (88). As mentioned above, a diet rich in cassava (which is
Research has reported an increased risk for thyroid dysfunction
a staple Nigerian food) has also been reported by certain studies
in parts of Central Africa where consumption of cassava
to be associated with goitrogenic effects (89). Animal studies
root and cassava flour is prevalent. Excessive intake of
have shown that milk exerts goitrogenic effects in certain areas
isothiocyanates along with a deficiency of dietary selenium can
of Finland (90).
lead to thyroid disorders.
Nursing.EliteCME.com Page 17
The effect of soy isoflavones on thyroid disorders
The active constituents present in soy foods are estrogenic in those cases where there is preexisting mild hypothyroidism
isoflavones, with genistein, daidzen, malonylgenistin and (80).
malonyldaidzin among the most common (81). Studies have
shown that soy isoflavones interfere with the activity of the Soy foods may also accelerate the underlying autoimmune
enzyme thyroid peroxidase, which is the primary enzyme process that is responsible for Graves disease and Hashimoto’s
involved in the synthesis of T3 and T4, thus, interfering with thyroiditis. A randomized, double blind, cross over study
their subsequent formation (79). Furthermore, the isoflavones where none of the subjects had prior thyroid surgery or
found in soy also prevent the uptake of iodine into the thyroid radioiodine therapy, showed that increased soy food intake
cells by interfering with the mechanism of the sodium-iodide corresponded with a relatively higher risk of TPO-negative
symporter (82). autoimmune subclinical hypothyroidism. There is no sufficient
data reporting the effect of long term exposure to soy foods
The phytoestrogens present in soy foods are known to interfere on thyroid function, although gastrointestinal side effects have
with the absorption of thyroid hormone from the stomach. been reported (80).
This effect may further worsen the thyroid function especially
Cruciferous vegetables
Cruciferous vegetables such as broccoli, brussels sprouts, with existing or past history of thyroid disorders must consult
cabbage, cauliflower, kale, kohlrabi, mustard, rutabaga their clinician before consuming large and regular quantity of
and turnips contain isothiocyanates. Isothiocyanates, like raw cruciferous vegetables such as broccoli.
isoflavones, are associated with a reduction in thyroid function.
Isothiocyanates also inhibit the enzyme thyroid peroxidase and
block neural messages across cellular membranes of thyroid
cells (86). Research into the role of cruciferous vegetables in
thyroid function points to the fact that increased intake of the
latter alone cannot cause thyroid disorders. However, those
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Nuts
The goitrogens in nuts inhibit the uptake of iodine and block
the binding of iodine to tyrosine, thus, inhibiting the synthesis
of thyroid hormones (88).
History
A personal history of any autoimmune disease slightly increases as the involvement of the genes lying in the HLA complex and
the risk of developing an autoimmune thyroid disease such as CTLA-4, smoking, stress and excessive iodine intake (92).
Hashimoto’s disease or Graves disease. Autoimmune thyroid
disorders are classic examples of organ specific autoimmune Thyroid disorders such as hypothyroidism are associated with
disorders. There are many factors, both genetic and raised levels of serum TSH alone while the presence of thyroid
environmental which give rise to autoimmune disorders such antibodies increases the probability of developing autoimmune
diseases (93).
Graves disease and Hashimoto’s thyroiditis are reported to Graves disease and Hashimoto’s disorders are closely related
be genetically distinct. Patients with Graves disease being autoimmune diseases which are known to cause thyroiditis
(97).
Graves disease
It is an autoimmune disorder which ultimately progresses to immune response induces the release of excess T4 and T3 into
overactivity of the thyroid gland, or hyperthyroidism. Graves the blood, thus, causing hyperthyroidism (98). Hyperthyroidism
disease, a hyperthyroid condition with diffuse goiter, is the most has also been mentioned as one of the symptoms of Graves
common cause of thyroid disease in the US (100). An abnormal disease (99).
Hashimoto’s disease
Chronic autoimmune thyroiditis has been classified in two The correlation between autoimmunity and autoimmune thyroid
forms; disorders
●● Goiterous form (often referred to as Hashimoto’s disease)
●● Atrophic thyroiditis Autoantigens produced and found in patients with autoimmune
thyroid disorder are recognized to exhibit intra and inter-
These two are characterized by the presence of thyroid individual heterogeneity. The cytokines produced indicate
antibodies in the serum and varying severity of thyroid the involvement of both the Th1 and Th2 limbs of the helper
disorders (100). Hashimoto’s disease sometimes has been T cell response. The secretion of chemokines and cytokines
known to occur as part of a complex condition called Type I in the thyroid helps in the accumulation and expansion of the
polyglandular autoimmune syndrome (101) intra-thyroidal lymphocyte pool. Thyroid cells themselves
are involved in this secretion. Along with chemokines
Nursing.EliteCME.com Page 19
and cytokines, thyroid cells also produce a number of destruction of the thyroid cells in autoimmune hypothyroidism.
proinflammatory molecules which enhances the autoimmune It also mimics the effect of death receptor mediated apoptosis
response. T cell mediated toxicity is responsible for the (102).
Drugs
There are drugs used in the treatment of different non- People who have thyroid antibodies before the start of therapy
thyroidal conditions that are known to adversely affect the are also at an increased risk of getting induced thyroid disorders
thyroid function. Often these effects on the thyroid function (103).
are their side effects. As discussed previously, these drugs
are amiodarone, interferon, lithium, kelp tablets and dietary Tyrosine kinase inhibitors are a class of drugs which are used
supplements. Patients taking these drugs should be monitored in the treatment of neoplasms such as thyroid cancer. Research
routinely for the presence of any thyroid disorders. The use has reported that they can cause thyroidal side effects. They
of iodide containing medicines can induce hyperthyroidism can adversely affect thyroid hormone metabolism and affect
within 3-8 weeks of administration. Iodides are known to patients who are being given thyroid replacement therapy
cause hypothyroidism but they may also induce goiter and (104).
hyperthyroidism (103).
Similarly immune modulators are also known to cause
According to research studies, the incidence of amiodarone- hyperthyroidism and hypothyroidism. Lithium has also been
induced thyroid disease is approximately 2 to 24 percent of known to bring about anti-thyroid effects; affect the absorption,
the population. The prevalence of hyperthyroidism has been metabolism and transport of thyroid hormones. Research
reported in 1 to 5 percent of the patients. There are two types studies have shown that lithium activates the production of
of hyperthyroidism induced by amiodarone, namely; Type 1 antibodies against thyroid cells and causes hypothyroidism
Graves disease and Type 2 subacute thyroiditis resulting from (105).
the direct toxic effect on the gland (103).
Salicylates like aspirin, salicylic acid, methyl salicylate, sodium
Likewise, there have been reports of patients taking lithium salicylate and diflunisal are known to affect the concentration
carbonate diagnosed with lithium-induced hypothyroidism of thyroxine in the blood. They displace thyroxine from the
and subclinical hypothyroidism. A research study has reported thyroxine-binding globulins and induce thyroid disorders.
a prevalence rate of 5 to 20 percent of patients, while other Topical products containing salicylates used to treat acne and
studies reported almost as high as 50 percent of patients. The skin disorders have not been reported to induce any thyroid
drug is also known to induce non-tender goiter. Lithium is disorder (106).
known to accumulate in the thyroid gland and adversely affect
There are also medications which affects the metabolism of T4.
the synthesis and release of thyroid hormones. The period
Drugs like rifampin, rifabutin, phenytoin, carbamazepine and
of exposure to lithium treatment is reported to be directy
phenobarbital are known to enhance the metabolic removal of
proportional to the risk of developing hypothyroidism (103).
T4 and T3 which creates complications in patients who require
Interferon-alpha used in the treatments of tumors and Hepatitis thyroxine replacement therapy. Similarly, the use of ritonavir
C has been known to cause autoimmune destruction of thyroid increases the glucuronidation of thyroxine, thus necessitating an
cells, leading to a modified level of thyroid hormones in the increase in the dose of thyroxine. The use of serotonin reuptake
blood stream. However, when interferon beta-1b is used in inhibitors (SSRIs) is also associated with modifications in the
treatment of multiple sclerosis, it is not known to induce requirements of T4. Other drugs adversely affect the absorption
thyroid dysfunction. The thyroid disorder that developed during of exogenous thyroxine. Drugs such as iron, aluminum-
interferon therapy is transient in nature according to research containing products (e.g. sucralfate, antacids, and didanosine),
reports (103). sodium polystyrene sulfonate, resin binders and calcium
carbonate have been reported to inhibit the absorption of
Research studies have reported that women are more affected exogenous thyroxine and reduce their efficacy as well (103).
by drug-induced thyroid disorders when compared with men.
Page 20 Nursing.EliteCME.com
Research has reported that the occurrence of thyroid carcinoma found that therapy with T3 supplement is not necessary for
is one of the most commonly prevalent malignancies in patients survival of the patients who have undergone transplantation
who underwent kidney transplant. Moreover, studies have also (107).
Subclinical state
The subclinical thyroid disorders are the preclinical stage of the levels below 0.45 μU per mL and above 4.50 μU per mL are
actual diseases; they don’t represent the disease itself. They are considered hyperthyroid and hypothyroid states, respectively.
considered strong predictors for thyroid disease. In fact, they If left untreated, both can lead to serious thyroid dysfunction.
are actually laboratory evident diagnosis with no symptoms. It is therefore crucial for the clinician to weigh in the risks and
The patient may remain completely asymptomatic or may feel benefits of each patient individually; i.e. will a potential initial
mild degrees of thyroid dysfunction at this stage. treatment do more harm than good or vice versa. (110)(111).
The subclinical thyroid disorders are classified into subclinical Each subclinical state will be discussed individually in the
hypothyroidism and subclinical hyperthyroidism. Both succeeding pages.
are laboratory diagnoses with nonspecific symptoms; TSH
Subclinical hypothyroidism
In subclinical hypothyroidism, the serum TSH level of the 5. Ear, nose and throat: Occasional swelling of the thyroid
patient remains slightly elevated without affecting the serum gland affects the speech of the patient which leads to voice
fT3 and fT4 levels, which remains within the normal range hoarseness and occasional hearing difficulties.
throughout this stage. 6. Female reproductive organ: Hormonal imbalance leads
to disturbance in the menstrual cycle, exhibiting as
As mentioned above, patients usually exhibit nonspecific menorrhagia and irregular menstruation.
symptoms. These are outlined in detail below (109): 7. Cardiovascular: Thyroid dysfunction may also manifest as
1. General: Fatigue even during routine work, lower energy bradycardia.
levels as compared to others, increased sensitivity to cold 8. Musculoskeletal: Patient may exhibit symptoms such as
temperature, unexplained mood swings, and unexplained muscle pain, fatigue, frequent and painful muscle cramps,
weight gain. and stiffness of the joints. Neck stiffness and back pain are
2. Skin and hair: Altered skin appearance. The skin becomes invariably present in many of the female patients.
dry and flaky. It may become pale or yellowish in 9. Laboratory findings: The findings usually show slight
appearance. Hairs also become dry, with apparent moisture elevations of serum TSH while serum Ft3 and Ft4 remain
loss and become brittle. within the normal range. Additionally, some patients may
3. Psychological: Thyroid hormone imbalance has extensive show slight abnormalities with their lipid profiles. They may
effects on the brain. Symptoms include constant exhaustion, have mildly elevated triglyceride and LDL levels.
mood swings, depression, irritability, unexplained angry
reactions, and loss of interest in the surroundings and day to
day work.
4. Gastrointestinal: Increased level of TSH level affects bowel
movement producing symptoms such as constipation,
indigestion and loss of appetite.
Nursing.EliteCME.com Page 21
Subclinical hyperthyroidism
Subclinical hyperthyroidism manifests with low or undetected cardiac function, the patient may become tachycardic
serum TSH level in the patient with normal T3 and T4 levels. and carry a higher risk of developing supraventricular
Its symptoms are discussed in detail below (109): arrhythmias. 2D echo often gives an evidence of left
1. General: Symptoms such as persistent fatigue, tremor, ventricular hypertrophy and impaired diastolic function.
malaise and reduced feeling of well being are very common. 6. Female reproductive organ: Decreased thyroid level may
The patient may also experience increased propensity lead to menstrual abnormality and even amenorrhea.
to sweat and greater intolerance to heat. The significant 7. Musculoskeletal: The patient may have reduced bone
symptom is unexplained weight loss. mineral density (BMD) accompanied by accelerated
2. Gastrointestinal: The patient may have frequent bowel osteoporosis and thinning of bones, making the patient
movements and increased appetite. susceptible to bone fractures. This symptom is very
3. Psychological: The patient may experience random mood common in post-menopausal women. Additionally, the
swings and fluctuating energy levels characterized by patient often complains of vague muscular pain and muscle
hyperactivity immediately followed by fatigue. Constant weakness.
nervousness, anxiety, fear, hostility and sleep disturbances 8. Neurological: Tremors, vertigo are some of the neurological
are seen in subclinical hyperthyroidism. Additionally, the symptoms of subclinical hyperthyroidism. Since it usually
patient may have difficulties concentrating. occurs in elderly women, it may be confused with age-
4. Skin and hair: Sweat glands become overactive and lead to related dementia and Alzheimer’s disease.
hyperhidrosis and hair loss. 9. Laboratory findings: The blood tests will show low or
5. Cardiovascular: Patient may experience palpitations. Since undetectable levels of TSH with T3 and T4 levels remaining
thyroid level affects the neurohormonal regulation of the within the normal range.
Symptomatic thyroid disease
Myxedema coma
Myxedema coma is a severe life-threatening complication of puffy, yellow skin, coarse hair, temporal loss of eyebrows,
hypothyroidism that usually presents with profound lethargy or prominent tongue) (111).
coma accompanied with hypothermia. It affects multiple organs
accompanied by progressive decline of mental function. There
may be bradycardia, hypotension, and myxedema faces (dull,
Page 22 Nursing.EliteCME.com
Hypothyroidism in infant and children
Hypothyroidism in children is not common but it can affect feeding difficulty, hoarse cry, slow activity, lethargy, thick
them. This is especially true to those born to mothers with tongue, swollen abdomen, constipation and increased sleep
thyroid dysfunction. Early detection is very important as (110).
delayed treatment can seriously impact their physical and
mental development. These days, babies are tested for Symptoms of hypothyroidism in children vary individually,
hypothyroidism. depending on the onset and present stage of the disease. Some
common presentations are prolonged jaundice, enlarged thyroid
Hypothyroidism may be difficult to diagnose in infants since gland, weight gain, slowness, learning difficulties, stunted
the presenting symptoms are quite general. These may include growth or failure to grow and delayed puberty (110).
Autoimmune hypothyroidism
Autoimmune hypothyroidism is most often associated with Additional symptoms such as constipation, difficulty
Hashimoto’s thyroiditis or chronic thyroiditis. The autoimmune concentrating or thinking, goiter, fatigue, heavy and irregular
destruction of the thyroid gland gradually slows down or menstruation, cold intolerance, joint stiffness, and mild weight
interferes with its metabolic functions. gain. Late in the disease, patients usually develop shrunken
thyroid glands.
Patients with Hashimoto’s thyroiditis may present with goiter
rather than symptoms of hypothyroidism. The goiter may not Reidel’s thyroiditis is a rare cause of chronic thyroiditis. The
be large but is usually irregular and firm in consistency. It onset of disease is insidious with painless goiter and local
is usually palpable upon physical examination. It is rare for pressure symptoms. Thyroid dysfunction is uncommon. Goiter
uncomplicated Hashimoto’s thyroiditis to be associated with is hard, non-tender, fixed and asymmetrical.
pain.
Another less common form thyroiditis is acute thyroiditis. It is
Patients with atrophic thyroiditis or late stage Hashimoto’s usually due to bacterial infection, rather than an autoimmune
thyroiditis present with obvious epidermal signs and symptoms response. There is painful swelling in the anterior neck, fever,
of hypothyroidism. The skin may be dry accompanied by and local pressure symptoms like dysphagia if associated with
decreased sweating, thinning of the epidermis, hair loss, and upper respiratory or systemic infection. The patient may remain
skin thickening without pitting (myxedema) (112). euthyroid but sometimes, transient hormonal dysfunction may
occur.
Nursing.EliteCME.com Page 23
The table below summarizes the most common presenting signs older age, anterior neck enlargement and pressure symptoms,
and symptoms per age group (113). stare, gritty sensation, increased lachrymal secretion, diplopia,
and diminished visual acuity (113).
Young patients Elderly patients
The signs of early onset hyperthyroidism are restlessness,
Sympathetic activation such Cardiovascularsymptoms
inability to keep still, objective weight loss, excessive sweating,
as anxiety, hyperactivity and such as dyspnea, weight loss
hair thinning and straightening, tachycardia, increased pulse
tremor and atrial fibrillation
pressure, ectopic beats, atrial fibrillation in elderly, sick sinus
The symptoms of early onset hyperthyroidism are anxiety, syndrome, cardiac failure, fine tremors, hyperreflexia, proximal
tremulousness, generalized weakness, weight loss with muscle weakness, periodic paralysis, gynecomastia, diffuse
increased appetite, diarrhea, oligomenorrhea, loss of libido, heat or nodular goiter, bruit, thrill, lid retraction, lid lag, chemosis,
intolerance, skin tanning, pruritus, palpitation, irregular beats, infiltrative ophthalmopathy, ocular muscle paresis, and
shortness of breath, hyperactivity, muscle weakness, apathy in exposure keratitis (113).
Thyroid storm
Thyroid storm is rare but is considered one of the most severe psychosis, and coma. Patients with thyroid storm may see
manifestations of hyperthyroidism. It is a result of untreated their condition progress to cardiovascular collapse and shock.
hyperthyroidism but may also be precipitated by infection, Atrial arrhythmias are common. Thyroid storm is a medical
trauma, surgery and diabetic ketoacidosis. emergency and is diagnosed based on clinical symptoms rather
than on laboratory results (114).
The signs and symptoms of a thyroid storm include fatigue,
high grade fever, tachycardia, dyspnea, restlessness, confusion,
Nodular goiter
Toxic nodular goiter such as those in Graves disease grows 1. Pattern of enlargement, duration and rate of growth.
from an existing simple goiter. It may present as circumscribed Short duration and rapid enlargement are consistent with
area of firmness with regular margin that is the palpable nodule neoplasm.
in the thyroid gland. It is usually more than 1 cm, as nodules 2. Associated local symptoms. Pain, dysphagia, dyspnea
smaller than this size are harder to palpate with certainty. or hoarseness of voice suggests extrathyroidal tissue
involvement.
The size, symmetry, contour, consistency and mobility of 3. Symptoms referring to hormonal status. Malignant
the thyroid nodule and extranodular thyroid tissue should nodules are not usually associated with hypothyroidism or
be defined. Thyroid nodules may be solitary or multiple and hyperthyroidism. Medullary carcinoma may be associated
functional or nonfunctional. with hyperparathyroidism and/or pheochromocytoma.
Generally, thyroid nodules may be benign or malignant. The
most effective way of initially differentiating between the two Physical examination should demarcate the dimensions of the
is conducting a thorough assessment of the patient history, thyroid nodule, whether it is single or multiple, the regularity of
laboratory and physical exam results. Particularly, the following its margins, consistency and movement to adjacent structures.
points are taken into consideration: A solitary nodule is more likely to be malignant than multiple
ones. Ill-defined margins, hardness and immobility are other
characteristics of malignancy.
Graves disease
Patients with Graves disease (diffuse toxic goiter) may and ophthalmopathy. Ophthalmopathy may be present with
present with exophthalmoses, retraction of upper eye-lid the following symptoms, blurring of vision, double vision,
and lid lag (thyroid stare). Graves disease is characterized photophobia, increased lacrimation. Additionally, skin problems
by diffuse goiter, thyrotoxicosis, infiltrative orbitopathy may also arise such as pretibial myxedema (115).
Page 24 Nursing.EliteCME.com
Toxic multinodular goiter
Plummer disease is a form of toxic multinodular goiter. All the present with palpitations, tachycardia, tremor, and weight loss
symptoms of goiter are present which may include subclinical and atrial fibrillation in the elderly.
hyperthyroidism or mild thyrotoxicosis. The patient may
Thyroid cancer
The signs and symptoms of thyroid cancers will be discussed ■■ Low-grade encapsulated
individually according to their classification below: ■■ High-grade Angio-invasive
■■ Hurthle cell
1. Well differentiated (good prognosis) 2. Medullary (from parafollicular cells)
a. Papillary 3. Anaplastic (undifferentiated)
■■ Minimal thyroid cancer 4. Lymphoma
■■ Invasive 5. Others (metastatic, epidermoid, teratoma, sarcoma)
b. Follicular
Papillary carcinoma
The size of the tumor varies significantly from microscopic structures such as the bones and lungs. Additionally, these
to several centimeters located at the center of the front of tumors may be multifocal and exhibit relatively slow growth
the neck. Most of these lesions are very small and spread and proliferation. Most of the time, there are no other
via the lymphatic system. Metastasis can also occur via the symptoms (117).
hematogenous route particularly to the nearby anatomical
Follicular carcinoma
The tumor varies from a well-differentiated, virtually normal- Follicular carcinoma tends to metastasize by the hematogenous
appearing thyroid tissue to nearly solid sheets of follicular route affecting the bones, lungs and the central nervous system
epithelium with sparse evidence of follicular formation. (118).
Anaplastic carcinoma
In microscopic examination, anaplastic carcinoma is body (distant metastasis). The tumor often extends locally and
characterized by poorly differentiated cells with very aggressive may result in tracheal compression (119).
proliferation, spreading fast to the neck and other parts of the
Medullary carcinoma
Medullary carcinoma produces and releases excess endocrinopathy. There are usually bilateral lesions associated
thyrocalcitonin and a protein called carcinoembryonic with pheochromocytoma and hyperparathyroidism (119).
antigen (CEA) into the blood. It is often without varying
Thyroid lymphoma
Thyroid lymphoma is usually of the nodular histiocytic form is its characteristic feature and suggestive of its diagnosis. A
of thyroid cancer. It often arises from the background of confirmed diagnosis is often possible only after open biopsy.
Hashimoto’s thyroiditis. A rapidly expanding thyroid mass Such tumors are radiosensitive (120).
Neuromuscular manifestations
Aside from cardiovascular, epidermal, endocrine, and since these are often masked by symptoms of other diseases.
physical signs and symptoms, thyroid disorders manifest with This is especially true in elderly patients because of the natural
neurological manifestations that should be considered by decline of bodily functions due to the aging process.
clinicians when suspecting a thyroid dysfunction diagnosis
Nursing.EliteCME.com Page 25
Thyroid disorders have protean clinical presentation with a therefore lead to neurological manifestations (121). In
variety of symptoms involving multiple systems of the body. some forms of thyroid disorders, the neurological signs and
Thyroid hormone plays a significant role in the development symptoms may be the only presentation of the disease. These
and functioning of central and peripheral nervous system. are discussed in detail below.
Abnormalities in production and release of thyroid hormones
Hypothyroidism
1. Headache: Headache is a commonly encountered 5. Cognitive symptoms: Gradual progressive dementia, altered
symptom in hypothyroidism. It usually presents as a sensorium and even frank coma are the major effects on
headache of unknown causes. The underlying cause is cognitive function.
attributed to the increased intracranial pressure brought 6. Cerebellum: Though rare, symptoms such as balance
on by hypothyroidism. In pediatric patients, subclinical difficulties, gait and posture problems may be seen.
hypothyroidism is associated with worsening of migraine Additionally, patients may have difficulty performing tasks
headaches (120). that require accuracy. In elderly patients, ataxia and tremor
2. Dizziness and tinnitus: Both are very common in can be a symptom of hypothyroidism (121).
hypothyroidism. In fact, they are often the earliest 7. Myopathic weakness: Hypothyroid patients may also
symptoms. Tinnitus usually resolves once the thyroid levels complain of neuromuscular symptoms such as muscular
normalize. stiffness, cramps and muscular pains with weakness (121).
3. Hashimoto encephalopathy (HE): Current evidence 8. Myoedema: This symptom refers to the mounding up
shows that encephalopathy develops in steroid-responsive of muscle tissues after light percussion. Although rare,
autoimmune thyroid disease (121). It is categorized into two muscle hypertrophy is also seen in the patient with
types, namely: hypothyroidism which is actually a pseudo-hypertrophy.
○○ First type: Characterized by acute episodes with Pseudo-hypertrophy can occur in all muscles of the body
transient focal neurological deficits and epileptic but is more often seen in the lower limbs especially the calf
seizures. muscles. The pseudo-hypertrophic form of hypothyroid
○○ Second type: Characterized by gradual onset of myopathy in adults is called Hoffmann’s syndrome (121).
progressive dementia, followed by psychosis and coma 9. Peripheral neuropathy: Forty percent of patients with
after several weeks. In this type, no focal neurological hypothyroidism show symptoms of sensory and motor
deficits are seen. neuropathy. Carpal tunnel syndrome is the commonest
4. Psychoneurological symptoms: These are the most common occurrence (121). The nerves of the lower limbs are
symptoms of hypothyroidism. These are mainly depressive more involved in peripheral neuropathy than the upper
symptoms, with major depression an often seen presenting counterparts. Median nerve entrapment and peroneal
feature. Additionally, other symptoms like mood swings, neuropathy can occur due to deposition of mucinous
anxiety and even the myxedema madness may be seen substance. The bilateral foot drop is another symptom of
(121). peripheral neuropathy.
Hyperthyroidism
1. Psychoneurological symptoms: It includes anxiety, ○○ Functional abnormality: This is due to overactivity of
restlessness, cognitive difficulties, and psychotic symptoms. the sympathetic nervous system.
Patients may also experience major depression (121). ○○ Infiltrative ophthalmopathy: This involves the orbital
2. Neuromuscular: Almost 80 percent of hyperthyroidism contents which presents serious outcomes.
patients have neuromuscular complaints, with 50 percent Additionally, ocular muscle paralysis is also seen in
of those experiencing muscular weakness. Generally, many patients. It results in the appearance of protruded
myopathy starts proximally, usually at the pelvic girdle then eyeballs from its sockets, a typical diagnostic feature of
progress to the distal muscles (121). Myalgia, fatigue and Graves disease. Strabismus and diplopia are other ocular
exercise intolerance are common findings in these patients. manifestations as well as pain and lid retraction. An increase
Additionally, they may often feel breathless, due to the in intraocular pressure and damage to the optic nerve are
involvement of respiratory smooth muscles. Tendon reflexes among the other manifestations of hyperthyroidism.
remain normal. 5. Myasthenia gravis: It is also an autoimmune disorder
3. Thyrotoxic periodic paralysis: It manifests as recurrent which often coexists with hyperthyroidism. Patients
episodes of hypokalemia and muscular weakness that lasts with myasthenia gravis have higher risk of developing
for days. The incidence is more common among males, hyperthyroidism. Fatigue is the main presenting symptom
with 11:1.2 male to female ratio. The paralytic attack starts (121).
with symptoms such as pain, cramping, stiffness followed
gradually by paralysis. The attack may last up to 48 hours.
Proximal muscles are more severely involved than the distal
ones (121).
4. Exophthalmic ophthalmoplegia: This is otherwise known as
Graves ophthalmopathy. There are two existing types (121):
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DIAGNOSIS
Physical exam
Usually, thyroid disorders are discovered during routine Using the results of the anterior and lateral inspection and
physical exam. A clinician inspects and palpates the neck using palpation, clinicians will proceed to categorize the gland as
the hands. If a palpable nodule in the anterior part is found, the (122):
clinician may possibly ask about the medical history such as a. Goiter ruled out [normal or small (1 to 2 times normal) with
radiation therapy and risk factors including family history. lateral prominence <2 mm ],
b. Goiter ruled in [large (& 2 times normal) or lateral
Additionally, clinicians will note the gland texture, mobility and prominence >2 mm] or
tenderness of nodules, if any. c. Inconclusive
Thyroid function tests
The most accurate way to assess thyroid function is through Reverse Reverse T3 20-80 ng/dL
blood tests measuring the TSH, anti-thyroid antibody and triiodothyronine
calcitonin levels. Another test, a more reliable type, done to Thyroglobulin Thyroglobulin < 60 ng/mL
assess the thyroid status is the measurement of free T4 (fT4) in
the blood. The fT4 and fT3 provide more accurate readings of As mentioned earlier, the thyroid gland secretes two iodine-
T4 and T3 levels, respectively. containing hormones, T4 and T3. It produces more T4, which
when released is converted in the peripheral tissues to T3,
According to the Journal of the American Medical Association the more active hormone. The production and secretion of T4
(JAMA), screening adults who are more than 35 years old for and T3 are stimulated TSH which is secreted by the anterior
mild thyroid failure is as cost-effective as screening for high pituitary gland. In turn, the release of TSH is stimulated by
cholesterol or high blood pressure (124). the hypothalamic hormone, thyrotropin releasing hormone
(TRH). Both T4 and T3 produce a negative feedback effect on
Below is a table of the summary of the various thyroid function
the pituitary and hypothalamus, regulating the TSH and TRH
tests and their reference values. Each one is discussed in detail
release, respectively. TSH is a good index of thyroid function
in the succeeding pages.
and is recommended as the primary screening test for suspected
thyroid diseases (123).
Thyroid function Entities being Reference values
test tested A reduction of thyroid hormone levels leads to increase in the
Total thyroid T4 4.5-10.5 μg/dL size and number of the thyroid follicular cells, an increased
hormones T3 60-181 ng/dL TRH and TSH secretion, and thus, stimulation of thyroid
hormone synthesis and release. Elevated thyroid hormone
Free thyroid fT4 0.9-2.1 ng/dL
levels stimulate the breakdown of TRH, resulting in the reduced
hormones ft3 0.1-0.3 ng/dL number of TRH receptors on pituitary cells, and inhibition of
TSH Euthyroid 0.35-5.5 mU/L the pituitary response to TRH stimulation. The overall result is
Hyperthyroid 0-0.35 mU/L reduced production and release of TSH until T3 and T4 levels
normalize (123).
Hypothyroid < 5.5 mU/L\
Anti-thyroid anti-thyroglobulin Negative Due to the high binding affinities of T4 and T3, only a very
antibodies anti-microsomal Negative small portion of the free physiologically active hormones
antibody circulates in the blood. It is worth noting that the concentration
of proteins that bind T4 and T3 vary widely between euthyroid
TSH-receptor None detected
individuals, making such measurements inconsistent and
antibody
sometimes, unreliable. Unbound T4 and T3 (fT3 and fT4)
thyroid stimulating Negative provide a better hint of the patient’s thyroid function than the
immunoglobulins total T3 and T4 levels. fT4 and fT3 are usually used to verify
(TSI) abnormal thyroid status indicated by the initial TSH screening
anti- Negative test (123).
thyroperoxidase
antibodies
TSH test
In most cases, the initial test conducted to assess thyroid suppressed, normal or elevated. Below is a summary of the
function is the measurement of TSH level in a blood sample. implication of each result.
The rationale behind this is to first determine whether TSH is
Nursing.EliteCME.com Page 27
Decreased TSH Normal TSH Elevation of TSH most healthy individuals, normal TSH values correspond to a
healthy and fully functional thyroid gland (124).
Overactive Normal thyroid Failing thyroid
thyroid gland: gland gland: Primary It is worth noting that in subclinical hypothyroidism, TSH
Hyperthyroidism, hypothyroidism levels may be borderline elevated with corresponding normal
secondary fT4 levels.
hypothyroidism
There are certain conditions in which TSH measurement can be
Elevated TSH level suggests failure of the thyroid gland misleading, namely;
due to direct deleterious effects (primary hypothyroidism).
On the other hand, low TSH level usually suggest an Common Rare
overactive thyroid and over-secretion of thyroid hormones
(hyperthyroidism). Occasionally, a low TSH may result from a Recent thyrotoxicosis TSH-secreting pituitary tumor
dysfunctional pituitary gland, which leads to underproduction Pituitary disease Thyroid hormone resistance
of TSH to stimulate the thyroid (secondary hypothyroidism). In
Non-thyroidal illness
Page 28 Nursing.EliteCME.com
under 20 mIU/L during the recovery phase from non- TSH measurements in inpatients and must only be ordered
thyroidal illness (236). Therefore, there are limitations to when thyroid dysfunction is strongly suspected (237).
T4 Tests
Circulating T4 exists in two forms (125): hypothyroidism will either have a decreased fT4 or FTI
1. T4 that is bound to carrier proteins that disables its entry levels. Combining the TSH test with the fT4 or FTI accurately
into body tissues that may require it and, establishes thyroid function.
2. Free T4 (fT4) freely enters the body tissues to exert its
physiological actions. The fT4 fraction is most important The finding of an elevated TSH and low fT4 or FTI indicates
in determining the status of thyroid function; the tests used primary hypothyroidism. It occurs when the pituitary gland
to measure this are called the free T4 (fT4) and the free T4 recognizes the underactivity of the thyroid gland and in
Index (fT4I or FTI). response, releases more THS in an effort to stimulate it to
produce thyroid hormones. If the thyroid gland is functioning
Measurements of fT4 and fT3 have largely replaced the need normally, it will not react to the stimulation, leading to elevated
for measurement of total T4 and total T3 levels. TSH levels with low fT4 levels. Low TSH and low fT4 or
FTI indicates hypothyroidism due to a dysfunctional pituitary
If TSH level is abnormal, fT4 is employed to arrive at a gland, a condition called secondary hypothyroidism. A low
conclusive diagnosis. Patients with hyperthyroidism will TSH with an elevated fT4 or FTI is found in individuals with
either have an elevated fT4 or FTI, whereas patients with hyperthyroidism.
T3 Tests
T3 is tested in cases of hyperthyroidism where the T4 levels request for both TSH and fT4 for an accurate evaluation of the
are within the normal range. T3 tests are especially helpful in thyroid function (125).
diagnosing hyperthyroidism or determining its severity. Patients
who are hyperthyroid will have increased T3 levels. In some In hypothyroidism caused by pituitary disease where the TSH
individuals with low TSH, only the T3 level is increased and remains within normal range or one which develops within 12
the fT4 or FTI levels remain normal. Measuring T3 levels is not months of treatment for thyrotoxicosis, the TSH value remains
useful in the hypothyroid patient, since it is the last test to show suppressed in individuals who are thyroid hormone resistant. In
abnormalities. For example, patients may experience severe these cases, testing of free thyroid hormones is recommended
hypothyroidism with an elevated TSH and decreased fT4 or in addition to the TSH.
FTI levels, but show normal T3 levels. In other scenarios such
If TSH level is abnormally low, a fT4 or fT3 assay should be
as during gestation or while on contraceptives, elevated levels
obtained, and in difficult cases when the suspicion of thyroid
of total T4 and T3 can happen. This is because the estrogens
dysfunction remains high, a combination of all three tests
increase the binding protein levels. In these cases, it is better to
(TSH, fT3, fT4) is usually enough to prevent misdiagnosis.
Gestational thyrotoxicosis (Positive pregnancy test) 3. Low or normal TSH, low fT3 or fT4
Nursing.EliteCME.com Page 29
4. Raised TSH, low fT4 or fT3 (Primary hypothyroidism) Subclinical autoimmune thyroiditis
Common Rare
Chronic autoimmune thyroiditis Iodine excess 6. Normal or raised TSH, raised fT4 or fT3
Common
Reverse T3
The inactive metabolite of T4 is called the reverse T3, 3, 5, is deiodinated to rT3 rather than T3. Measuring rT3 levels in
5’-triiodothyronine (rT3). During acute febrile illnesses, chronic amniotic fluid might be a helpful tool in assessing fetal thyroid
hepatic cirrhosis, and other miscellaneous chronic systemic function because rT3 is the major metabolite of T4 in the fetus.
illnesses, its level increases, especially in infants. These patients The serum reference ranges for rT3 in adults and children are
will exhibit low T3 levels even at euthyroid states because T4 30 - 80 and 20 - 70 ng/dL, respectively (123).
Thyroglobulin
Thyroglobulin (Tg) is a glycoprotein produced by both normal monitoring of patients who underwent thyroidectomy for
and cancerous thyroid cells. It does not measure thyroid thyroid carcinoma. If the whole thyroid is removed, a procedure
function nor diagnose thyroid carcinoma in the presence of called total thyroidectomy, the Tg level normally reads at zero.
an intact thyroid gland. It is most useful in the postoperative Tg does not assess thyroid hormone function (123).
Ultrasonography (US)
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Once a thyroid nodule is palpated, the first imaging modality ●● Dependence on the ultrasonographer for the quality of
ordered by clinicians to corroborate lab test results and physical images, areas of the neck covered, and interpretation of the
findings is ultrasonography. It is readily available, cost- results
effective, and noninvasive, and requires no radiation exposure.
Ultrasonography is effective at thoroughly tracing the intra- In the recent years, there have been features added to
thyroidal architecture, differentiating cystic from solid lesions, the ultrasonographic scanning techniques to enable the
determining nodularity, and accurately pinpointing the exact identification of a higher risk of malignancy within a nodule,
location and measurement of a nodule (127). Other advantages including microcalcifications and central blood flow (129).
include the demonstration of associated lymphadenopathy, Sequential ultrasonographic scans allow clinicians to monitor
if any, in the paratracheal region, the most common site of disease progression, assess therapeutic outcomes, and identify
metastatic lymph node involvement (128). There are three recurrence.
drawbacks associated with ultrasonography scans, namely;
It should be noted that ultrasonography results can be
●● Its inability to provide any functional information of the
misleading if lateral neck nodal areas are not fully inspected for
thyroid gland
nodal disease (130).
●● Inability to predict malignancy
Nursing.EliteCME.com Page 31
cytological sample that is commonly associated with follicular of the final pathology being different from the frozen sample
neoplasms and Hürthle cell neoplasms. PTCs may also be obtained. Due to the nature of follicular thyroid carcinoma and
part of this classification when some nuclear features are seen, Hurthle cell carcinoma, a diagnosis using this approach cannot
but cytological evidence is insufficient to make a definitive be done. Therefore, when follicular or Hürthle cell neoplasms
diagnosis. There are several factors that increase the probability are strongly suspected, the best surgical option is to perform
of malignant follicular neoplasms, namely (140); hemithyroidectomy minus the frozen section succeeded by a
●● Nodule size greater than 4 cm complete thyroidectomy if the final pathology is confirmed for
●● Solitary nodule malignancy.
●● Male sex
●● Fixed nodule on palpation Non-diagnostic: Non-diagnostic aspirates are samples that
provide insufficient cytological material for a confirmed
If the aspirate is strongly suspected for PTC, a diagnosis. Patients should be made aware of the result being
hemithyroidectomy can be performed and sent for frozen neither positive nor negative; that no diagnostic material was
section. If the frozen section confirms it, a complete found in the sample obtained. In cases where two consecutive
thyroidectomy is then performed. Patients are advised FNA resulted in nondiagnostic findings, a surgical excision may
preoperatively about the surgery; with the frozen section being be a reasonable alternative.
only a representative sample of the tumor, with the possibility
US-Guided FNA
US-guided FNA is helpful in small nodules, usually <1.5 cm or cases when US-guided FNA was employed compared with 85.9
when a previous aspiration attempt was unsuccessful. Studies percent of cases when palpation alone was employed (141).
have shown that a diagnosis was achieved in 91.5 percent of
TREATMENT
Treatment approaches vary between individuals, depending satisfying, as most patients can be either cured or have their
on the type of disorder, comorbidities, severity and other diseases controlled.
factors. Treatment of thyroid disorders in general is extremely
Hypothyroidism
There is common consensus that patients with primary variability between refills (146) (147). The daily dose of
hypothyroidism with TSH levels over 10 mIU/L should be L-thyroxine depends on the patient’s age, sex, and body mass.
treated (142). However, there is less certainty about treatment When calculating doses, the ideal body weight is employed
protocols in patients with TSH levels of 4.5–10 mIU/L (143). because lean body mass is the best predictor of daily drug
There are a couple of initial studies done on patients with requirements (147). L-thyroxine administered with water an
subclinical hypothyroidism (TSH levels between 2.5 and hour prior to breakfast or at bedtime 4 hours after the last meal
4.5 mIU/L), that suggest beneficial response in reduction on an empty stomach exhibit superior absorption profiles.
of atherosclerosis risk factors such as atherogenic lipids, Although L-thyroxine is better absorbed when administered
impaired endothelial function, and intima media thickness. an hour before meals compared to half an hour before meals,
However, there are no solid clinical data supporting the patient adherence may be improved by instructing patients to
treatment of such patients, with pregnant women as the only consistently drink it with water between 30 and 60 minutes
exception. Spontaneous miscarriage during the first and second before breakfast.
trimesters of gestation and stillbirth later on in the pregnancy
are associated with increase in anti-thyroid antibody-negative L-thyroxine should not be taken with medications or food that
women with subclinical hypothyroidism. interferes with its absorption and metabolism. The table below
lists some of the most common ones.
Treatment of the hypothyroid patient is straightforward and Bileacidsequestrants(colestip High fiber diet
consists of hormone replacement. The standard drug used is ol, cholestyramine)
synthetic L-thyroxine sodium preparations which must be
Sucralfate Soybean
customized to the individual patient (144).
Ferrous sulfate Espresso coffee
Because of the sensitivity of the dosage requirements, Grapefruit juice Calcium salts found in
uniqueness of the various dosage formulations available in multivitamins
the market (e.g. liquid-containing capsules with the inactive
Proton pump inhibitors Chromium picolinate
ingredients gelatin, glycerin, and water) and uncertainty about
(omeprazole)
true interchangeability among the various formulations, current
guidelines encourage the use of one L-thyroxine preparation H2 antagonists (ranitidine) Phosphate binders
per patient throughout the duration of therapy to minimize (sevelamer)
Page 32 Nursing.EliteCME.com
Patients who are unable to take in L-thyroxine orally may subclinical hypothyroidism do not require full replacement
be given 70 percent or less of their usual dose intravenously. doses. Instead, they may be given doses of 25–75 μg/kg/day to
Crushed tablets of L-thyroxine suspended in water can be reach euthyroid levels, with the higher doses reserved for those
administered through enteral feeding via NGT. with higher TSH values (149).
Patients with minimal thyroid dysfunction, a full replacement Nutraceuticals in the form of desiccated thyroid has not been
dose of approximately 1.6 μg/kg/day of L-thyroxine is usually systematically studied in the treatment of hypothyroidism.
sufficient while patients who underwent total thyroidectomy Absorption profiles of orally administered dessicated thyroid
and/or radioiodine therapy and with central hypothyroidism differ between brands and origins (e.g. porcine or bovine).
may require higher doses. Patients with subclinical
hypothyroidism or who underwent treatment for Graves disease L-triiodothyronine in combination with L-thyroxine is another
may require a lesser dose. Young healthy adults can be started treatment option in hypothyroidism.
on full replacement dose. This treatment approach to initial
A study by Adrees et al. strongly suggests that treatment
therapy results in rapid normalization of serum TSH compared
of subclinical hypothyroidism can significantly reduce
to lower doses. Both doses, however, provide similar time for
atherosclerosis (150).
symptom resolution (148). On the other hand, patients with
Hyperthyroidism
Treatment of hyperthyroidism depends on its etiology, severity
and other factors. When diagnostic work up points to thyroiditis
Clinical recommendation Evidence rating
as the underlying cause, symptomatic treatment is usually
sufficient because of its transient nature. Graves disease, toxic The choice of radioactive C
multinodular goiter, and toxic adenoma can be treated with iodine, antithyroid
radioactive iodine ablation (treatment of choice in the US), anti- medication, or surgery for
thyroid drugs, or thyroidectomy. The latter is an option when hyperthyroidism should
other treatments have failed or are contraindicated, or when be based on the cause and
a goiter compresses adjacent viscera and cause symptoms. severity of the disease as well
Generally, the purpose of anti-thyroid drugs is to reduce thyroid as on the patient’s age, goiter
activity and hormonal effects which are responsible for the size, comorbid conditions,
presenting symptoms (151). and treatment desires.
Total thyroidectomy is C
Special treatment approaches are considered in patients who are recommended only for
pregnant or breastfeeding, with Graves ophthalmopathy, and patients with severe disease
amiodarone-induced hyperthyroidism. or large goiters in whom
recurrences would be more
Special circumstances such as the presence of coexisting
problematic.
ophthalmopathy in patients with Graves disease may also
influence the choice of therapy since radioactive iodine may Nonselective beta blockers C
aggravate the ophthalmopathy. Although younger patients such as propranolol (Inderal)
with hyperthyroidism often can be treated effectively with should be prescribed for
radioactive iodine, medical therapy with anti-thyroid drugs to symptom control because
reduce thyroid hormone levels is preferred. In younger patients they have a more direct effect
with very large goiters, thyroidectomy is a viable alternative. on hypermetabolism.
In older patients or those with cardiac disease, radioactive
The evidence rating is coined by the American Academy of
iodine usually is recommended after the patient has been
Family Physicians. Each rating is discussed in detail below
rendered euthyroid with anti-thyroid medications. Recombinant
(151).
human TSH is available for stimulation of radioactive iodine
uptake (RAIU) and release of thyroglobulin in patients with A = consistent, good-quality patient-oriented evidence
thyroid cancer after thyroidectomy. It has mostly eliminated
hypothyroidism after thyroid hormone withdrawal for patients B = inconsistent or limited-quality patient-oriented evidence
who undergo a total body scan and serum thyroglobulin
measurements to determine the presence of residual tissue. C = consensus, disease-oriented evidence, usual practice, expert
opinion, or case series
Below is a table with key clinical practice recommendations
with corresponding evidence ratings (151).
Nursing.EliteCME.com Page 33
Anti-thyroid drugs and other thyroid inhibitors
Anti-thyroid drugs and other thyroid inhibitors interfere, 3. Elevated levels of iodine to reduce thyroid hormonal
directly or indirectly, with the production, secretion, or synthesis and secretion
physiological effects of T3 and T4. Some have been used for 4. Radioactive iodine which kills cancerous cells with the use
more than a decade to control hyperthyroidism. These drugs are of ionizing radiation
grouped into four main classes:
1. Anti-thyroid drugs which directly block thyroid hormone Adjuvant therapy with drugs that do not affect thyroid
synthesis hormonal function is useful in controlling the clinical signs and
2. Ionic inhibitors which inhibit the iodide transport system symptoms of thyrotoxicosis. Specifically, these are inhibitors
of peripheral conversion of T4 to T3, b-adrenergic receptor
antagonists, and calcium channel antagonists (152).
Anti-thyroid drugs
The anti-thyroid drugs with clinical value are the thioureylenes, after which dose reduction may be considered to maintain
which belong to the family of thionamides. Propylthiouracil normal thyroid function. Disease control is achievable with low
(PTU) is its prototypical compound. Other commonly used doses, some patients showing thyroid function normalization
anti-thyroid drugs currently are methimazole and carbimazole, at daily doses of 5 to 10 mg of methimazole or 100 to 200 mg
the latter is a carbethoxy derivative of methimazole which is of propylthiouracil. After the first three to six months, follow-
converted to it after absorption. up intervals can be increased to every two to three months and
then to every four to six months.
Anti-thyroid drugs inhibit the formation of thyroid hormones by
interfering with the incorporation of iodine into tyrosyl residues In addition to blocking hormone synthesis, propylthiouracil
of thyroglobulin. They also inhibit the coupling of these partially blocks the peripheral conversion of T4 to T3.
iodotyrosyl residues to form iodothyronines. These inhibitory Methimazole does not exhibit the same actions; and though the
actions imply their interference with the peroxidise-mediated significance of this inhibition has not been firmly understood, it
oxidation of iodide ion and iodotyrosyl groups. The anti-thyroid gives a sound foundation for the preference of propylthiouracil
drugs bind to and inactivate the enzyme peroxidase only when over other anti-thyroid drugs in the treatment of severe
the enzyme is in the oxidized state. Over a period of time, hyperthyroidism or thyroid storm, where a reduced conversion
the inhibition of hormone synthesis results in the depletion of rate of T4 to T3 is therapeutically beneficial. Propylthiouracil
iodinated thyroglobulin stores as the proteins are hydrolyzed is the drug of choice in pregnant women since methimazole
and the hormones released into the circulation (151). is associated with congenital abnormalities. Its initial dose is
100 mg thrice a day with a maintenance dose of 100 to 200 mg
Methimazole usually is the drug of choice in non-pregnant daily (155). Both propylthiouracil and methimazole are rapidly
patients because of its cost-effectiveness, longer half-life, and absorbed from the gastrointestinal tract.
reduced incidence of agranulocytosis. The initial dose is 15 to
30 mg per day which may be given with a beta blocker such as When measured, the duration of organification of radioactive
propranolol. The beta blocker can be tapered off after four to iodine by the thyroid gland will usually show an effective
eight weeks and the methimazole adjusted, according to clinical absorption rate of approximately 20 to 30 minutes following
status and monthly fT4 or fT3 levels, toward an ultimate an oral dose of propylthiouracil. The inhibitory effect of a dose
euthyroid state requiring only maintenance doses of 5 to 10 mg of 100 mg of propylthiouracil starts to decline at 2 to 3 hours,
per day (153) (154). TSH levels tend to remain undetectable for with its 500 mg dose being only effective for 6 to 8 hours after
months after the normalization of thyroid hormone levels and intake. A single dose of 10 to 25 mg is needed to maintain its
should not be the test used to monitor therapy. At one year, if minimum plasma concentration up to 24 hours.
the patient shows clinical and biochemical normal accompanied
by an undetectable thyroid-stimulating antibody level, therapy The plasma half-life of propylthiouracil and methimazole
may be discontinued. However, if the latter is elevated, the are approximately 1.25 hours and 4-6 hours, respectively.
clinician may need to consider continuing therapy for another The drugs accumulate in the thyroid gland; methimazole
year. While some patients respond well to therapy, there are accumulates in the organ after carbimazole administration.
also higher rates of relapses reported. Drugs and metabolites are excreted via the kidneys and
appearmostlyintheurine.
Drug-induced hypothyroidism indeed can develop in patients
with mild hyperthyroidism taking high doses of methimazole.
In contrast, insufficient doses can very well result to under
treatment and unresolved hyperthyroidism. After initiation of
therapy, the patient’s thyroid function needs to be monitored
closely and tested regularly, preferably every four to six weeks
until thyroid function has been restored. Usually, after 4 to
12 weeks of treatment, most patients show significant clinical
improvements with some showing normal thyroid function,
Page 34 Nursing.EliteCME.com
Side effects
The side effects associated with propylthiouracil and Symptoms of overdose may occur, namely;
methimazole are relatively low. The development of ●● Change in consciousness
agranulocytosis with methimazole is suspected to be dose- ●● Cold, clammy skin
related; however, the same dose-response is not seen with the ●● Confusion
use of propylthiouracil. ●● Disorientation
●● Fast or weak pulse
The most common adverse reaction is a mild, occasionally ●● Light-headedness
purpuric, urticarial papular rash. It often subsides spontaneously ●● Loss of consciousness
without requiring treatment, but it sometimes calls for the ●● Sudden headache
administration of an antihistamine or changing to another drug. ●● Sudden loss of coordination
Other less frequent complications are pain and stiffness in ●● Sudden slurring of speech
the joints, paresthesias, headache, nausea, skin pigmentation,
and loss of hair. Drug fever, hepatitis, and nephritis are rare, If the symptoms do not subside after some time or worsen,
although abnormal liver function tests are often seen with medical help should be sought immediately and hormonal re-
higher doses of propylthiouracil (156). assessment done for possible dosage adjustment.
Remission
There have been various attempts to put in place more effective after completing a course of drug treatment than those with milder
therapeutic protocols for the use of anti-thyroid drugs to improve disease and smaller goiters.
the likelihood of remission, including the alteration of the dose
and length of treatment, and combining anti-thyroid medications If anti-thyroid drugs have immunosuppressive effects, a higher
with thyroxine therapy. Research have shown that patients with dose or longer treatment duration may improve the likelihood
severe forms of hyperthyroidism, extensive gland enlargement, or of remission. Treatment with anti-thyroid drugs for 12 to 18
high serum T3-T4 ratio to be less likely to proceed to remission months is the usual practice, as recommended in a recent
systematic, evidence based review (159).
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Ionic Inhibitors
The term “ionic inhibitors” designates substances that interfere for oral administration. Sodium iodide 123I is available for
with the concentration of iodide by the thyroid gland. The scanning procedures.
effective agents are anions that resemble iodide; monovalent,
hydrated anions of a size similar to that of iodide. The Radioactive iodine treatment for hyperthyroidism is usually
most studied example, thiocyanate, differs from the others indicated in older patients and those with heart disease.
qualitatively as it is not concentrated by the thyroid gland, Additionally, it is the best form of treatment when Graves’
but when given in large doses may inhibit the organification disease has persisted or recurred after partial thyroidectomy and
of iodine. Thiocyanate is produced following the enzymatic when prolonged treatment with anti-thyroid drugs has not led
hydrolysis of certain plant glycosides (161). to remission. Finally, it is also indicated in patients with toxic
nodular goiter, since the disease does not go into spontaneous
Among other anions, perchlorate (ClO4) is ten times more remission. Since therapeutic outcomes are not seen right after
active than thiocyanate. Perchlorate blocks the entrance of radioactive iodine treatment, clinicians often require patients to
iodide into the thyroid by competitively inhibiting the NIS. continue with anti-thyroid drug treatment until positive results
Although perchlorate can be used to control hyperthyroidism, are confirmed. Hypothyroidism symptoms are usually seen
it has caused fatal aplastic anemia when given in excessive within 2 to 3 months of radioactive iodine ablation therapy. If
amounts (2 to 3 g daily). Over the past few years, however, complete ablation fails 6 months after the radioactive iodine
perchlorate in doses of 750 mg daily has been used in therapy, repeated treatment is recommended (162).
the treatment of Graves disease and amiodarone-induced
thyrotoxicosis (161). The main contraindication for the use of 131I therapy is
pregnancy. Passage of TRAb through the placenta can cause
Radioactive iodine ablation therapy fetal hyperthyroidism. After the first trimester, the fetal thyroid
Radioactive iodine ablation therapy is commonly used in will concentrate the isotope and thus suffer damage; even
the treatment of hyperthyroidism and diagnosis of thyroid during the first trimester, radioactive iodine is best avoided
dysfunction. Sodium iodide 131I is available as a solution or because there may be adverse effects of radiation on fetal
in capsules containing essentially carrier-free 131I suitable tissues (163) (164).
Surgical intervention
Patients with thyroid disorders, in the course of treatment A study by Verloop et al. found that older patients with anti-
may be candidates for surgical management due to various thyroid peroxidase antibodies, elevated preoperative TSH levels
reasons. One of the main reasons is ineffective pharmacological and thyroiditis within the excised thyroid gland are at particular
treatment and unsuccessful medical management, particularly risk of developing hypothyroidism after a surgical lobectomy.
in patients with overactive thyroid glands (hyperthyroidism). As a result, clinicians need to monitor thyroid function
The patients with comorbidities or pregnant and requiring regularly since hypothyroidism may still develop even years
urgent normalization of thyroid function are often the right after surgery (171).
candidate for the surgical treatment. Thyroidectomy is rarely
indicated in Graves disease in the US. Thyroid surgery is 3. Isthmectomy: It refers to surgical removal of the band tissue
unavoidable in diagnosed thyroid cancer. Even the patient with (isthmus) connecting the two lobes of the thyroid gland. A
benign thyroid nodule (goiter) may also require thyroid surgery study by Perez-Ruis et al. found the feasibility and efficacy
due to the compressive symptoms (breathing and swallowing of isthmectomy in the treatment of solitary thyroid nodules
difficulties) caused by large nodules. confined to the isthmus (167).
There are various surgical options available for patients with 4. Completion thyroidectomy: It refers to the surgical removal
thyroid disorders, namely; of the remaining portion of the thyroid gland. It is usually done
after thyroid lobectomy when the thyroid tissues are suggestive
1. Total thyroidectomy: It is reserved for thyroid cancer, severe of thyroid cancer. A study by Rafferty et al. concludes it as
thyroid disease, multinodular goiter and substernal goiter. It a safe and appropriate option in the management of select
carries the risk of hyperparathyroidism and laryngeal nerve patients with well-differentiated thyroid cancer in which
damage (165) (166). In subtotal thyroidectomy, some of the a definitive preoperative or intraoperative diagnosis is not
thyroid tissues are preserved while reducing the incidence of available. The operation usually entails longer recovery period
hypothyroidism to 25 percent. Patients are then put on lifelong and thus, hospitalization (168).
replacement therapy with thyroid hormones.
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Minimally Invasive Thyroid Surgery
Minimally invasive thyroid surgery, as the name implies, is through a 2 cm incision. Its main advantage is a further
primarily defined by the reduced incision length which can be reduction of incision length, minimal anatomic manipulation
achieved by modifying the traditional surgical techniques or by and better visualization. As a result, patients are able to go
the use of endoscopes. home after a 6 hour observation period in the recovery room.
Patients who are asked to stay overnight generally have very
The patients who are good candidates for this procedure are large goiters, advanced cancer, bleeding disorders.(169).
those with:
●● Thyroid cancers less than 2 cm A meta-analysis by Radford et al. found the safety of MIVAT to
●● Thyroid nodules less than 3.5 cm be comparable to that of the existing gold standard operation.
●● Smaller goiters Additionally, it provides better cosmetic and pain outcomes for
●● Glands free of thyroiditis patients when compared to standard thyroid operations. MIVAT
is a promising new technique, with obvious benefits over the
Minimally Invasive Video Assisted Thyroidectomy (MIVAT) is established surgery, for small-volume thyroid disease that
a technique where part of the surgery is done with an endoscope mainly affects a young female patient population (170).
Nursing.EliteCME.com Page 37
Post- operative observation is required for up to 6 to 8 hours ●● Hypocalcemia: The 4 parathyroid glands lie behind the
after surgery. thyroid gland and regulate blood calcium levels. Injury or
●● Laryngeal nerve injury: The recurrent laryngeal nerve accidental removal of these glands results in hypocalcemia.
(RLN) which innervates the vocal cords passes just behind ●● Wound infection: Infection at the incision site is very rare
the thyroid gland bilaterally. Mechanical injury to the nerve (less than 1%) . Postoperative infection usually manifest
such as complete or partial transection, traction, contusion, as superficial cellulitis or as an abscess. Additionally,
crush, burn, misplaced ligature, and compromised blood erythema, warmth, and tenderness of the neck skin around
supply during surgery affects the cords and may result in the incision may be observed.
temporary voice hoarseness which usually resolves within ●● Seroma: Seroma is a collection of fluid under the incision.
a few days. There have been reported cases of occasional In most cases, seroma resolves within a few days after
permanent changes to voice after laryngeal nerve injury. surgery.
A serious consequence of a RLN injury is true vocal-fold
paresis or paralysis.
Chemotherapy
Unlike other forms of cancer, the key treatment for the majority Indications of chemotherapy for papillary and follicular
of thyroid cancer is not chemotherapy. Chemotherapy is usually carcinoma
not the first line of treatment used for thyroid cancer. The The treatment of papillary and follicular carcinoma of the
reason is that better outcomes are seen with thyroid surgery in thyroid involves surgical removal of the thyroid gland followed
combination with radiotherapy. Chemotherapy is occasionally by radioactive iodine and hormonal replacement therapy. But
used in the treatment of advanced thyroid cancer or thyroid when metastatic disease has already been established, there are
cancer that has reappeared and increased in severity after the minor chances of completely curing the disease. In such cases,
primary treatment. Additionally, chemotherapy can be given external radiotherapy and TSH suppression takes the lead role.
to patients with thyroid cancer as an experimental treatment If this approach also fails to stop disease progression, then
during clinical trials to chemotherapeutic drugs for various chemotherapy may be considered (174).
types of thyroid cancers (174).
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recurrent or progressive disease. However, chemotherapies improved, but yet unable to develop any standard protocol
have benefited the thyroid cancer patients with pulmonary, of the chemotherapeutic management of the thyroid cancer
bone or nodal metastasis and quality of life of patients have patients (177).
Physical exam
The physical exam for the thyroid gland consists of palpation to the sternocleidomastoid muscle. The ipsilateral lobe can
and inspection. be palpated simultaneously with the thumb or with the other
hand from the opposite direction.
Techniques (178): 4. When standing behind the patient, identify the landmarks
1. The location of the thyroid is identified by inspection. and isthmus with one hand, and when in position to feel
2. Using the anterior or posterior approach, palpate the thyroid the thyroid lobe on that side, place the fingers of the other
to identify nodules hand symmetrically on the other side of the trachea. Again,
3. Note the size and number of nodules. identify each lobe while the patient swallows. Feel the
4. Note the consistency of the nodule. gland’s surface, note any asymmetry, texture, and estimate
5. Palpate regional lymph nodes for consistency and mobility. the size of each lobe (normally 7 to 10 g). When goiter is
present, measure any discrete masses as well as the neck’s
According to Smith, the examination proceeds in the following
greatest circumference. A penciled tracing of the goiter’s
ways (178):
outline provides a reliable record for future comparison.
The patient should hold a glass of water and seated comfortably One should also palpate the neck for lymphadenopathy.
and the examiner positioned strategically, with plenty of room
Combining the physical examination of the thyroid gland
to move around the seated patient.
with proper evaluation of associated signs and symptoms is
1. Place the patient’s head in slight hyperextension with good
the best way to monitor disease process. There is no direct
cross light falling on the anterior neck and then ask the
correlation between size and function. A person with a goiter
patient to swallow. The outline of the thyroid gland in thin
can be euthyroid, hypothyroid or hyperthyroid. Monitoring
individuals can be observed frequently as a protuberance on
the response to therapy directed at decreasing the size of the
both sides of the trachea moving, 2 cm below the crest of
thyroid in cases of symptomatic goiter (179).
the thyroid cartilage.
2. Look for abnormal enlargement, contour, asymmetry, In addition of the thyroid gland itself, the physical examination
and masses while the patient swallows repeatedly. The should include signs of abnormal thyroid function and extra-
neck should also be inspected for abnormal masses and thyroidal features such as ophthalmopathy and dermopathy. In
prominent pulsations. Note the size and number of nodules. Graves’ disease, monitor lid retraction, periorbital edema and
Note the consistency of the nodule. Palpate regional lymph proptosis (179).
nodes for consistency and mobility.
3. Frequently it is advantageous to examine the gland while Assessment of the enlarged nodule and multiple nodules are
standing behind the patient. Identify the thyroid cartilage, required in diffuse non-toxic goiter and non-toxic multinodular
the thyrocricoid membrane, and the cricoid cartilage, a goiter, respectively.
horizontal structure 5 mm wide that marks the superior
border of the isthmus. Palpate the isthmus (frequently Other aspects of the clinical examination for thyroid disease
impalpable unless enlarged), and if standing to the side include (179):
of the patient, slide the tips of fingers so that their palmar
surfaces rest on the trachea with the dorsal surface medial
Nursing.EliteCME.com Page 39
Reflexes: The area near the Achilles tendon is struck with Examination of the eyes: The eyes are commonly affected by
a small mallet to test the reflex. Hyper-responsiveness may thyroid disease. The ocular symptoms are (179):
point to hyperthyroidism, and slow reflexes may indicate ●● Bulging or protrusion of the eyes
hypothyroidism. ●● Stare in the eyes
●● Retraction of upper eyelids
Cardiovascular integrity: Bradycardia may point to ●● A wide-eyed look
hypothyroidism, and tachycardia may indicate hyperthyroidism. ●● Infrequent blinking
Other patients with hyperthyroidism may also have ●● Lid lag
hypertension and arrhythmias such as atrial fibrillation.
Quantity and quality of hair: Significant hair loss is observed
Weight monitoring: Rapid and unexplained weight gain can in both hyperthyroidism and hypothyroidism. Coarse, brittle or
point to hypothyroidism, and rapid unexplained weight loss straw-like hair can point to hypothyroidism. Thinning, finer hair
may be a sign of hyperthyroidism. may point to hyperthyroidism (179).
Basal body temperature: Low body temperature is encountered Examination of cutaneous features: Hyperthyroidism manifests
in some patients with underactive thyroid gland. itself in different skin-related signs such as yellowish, jaundiced
complexion, unusually smooth, young-looking skin, blisters
Examination of the face: Hair loss along the outer edge of the
around the face, hives, and lesions or patches of rough skin on
eyebrows, and puffiness or swelling of the eyelids or face are
the shins (pretibial myxedema) (179).
other common symptoms of hypothyroidism.
Hyperthyroidism also shows signs on the nails and hands such
as (179):
●● Onycholysis: separation of the nail from the underlying nail
bed, also called Plummer’s nails
●● Swollen fingertips, also called acropachy
Review of other Clinical Signs
Evaluation and assessment of other clinical signs of Evaluation and assessment of other clinical signs of
hyperthyroidism include (179): hypothyroidism include:
●● Tremors ●● A dull facial expression
●● Shaky hands ●● Slow movement
●● Hyperkinetic movements -- table drumming, tapping feet, ●● Slow speech
jerky movements ●● Hoarseness of voice
●● Edema (swelling) of the hands and/or feet
TSH
Since thyroid disorders have diverse clinical manifestations, Patients who are not known to have a disturbance of
clinicians need to stay vigilant for subtle and nonspecific signs hypothalamic-pituitary function and have been on thyroid
and symptoms. To aid in this endeavor, frequent laboratory replacement therapy for longer than three months with TSH test
investigations are part of the essential tools to monitor therapy performed in the previous year have:
and disease progression. 1. TSH that is usually the sole initial test of thyroid function
2. TSH result within the reference range
TSH screening test is used not just in the diagnosis but also
monitoring ongoing therapy for thyroid disorders. It is the People who have been treated for thyroid cancer benefit from
most reliable screening test for monitoring ongoing therapy having a suppressed TSH, because TSH is thought to promote
for hypothyroidism and hyperthyroidism. The higher the level tumor recurrence.
of TSH, the higher the amount of T4 and T3 released into the
blood (180). High T4 with suppressed TSH levels suggests overtreatment.
Suppression of TSH with serum T4 at the upper end of the
Response to L-thyroxine (levothyroxine sodium) is best normal range or even slightly elevated is sometimes observed
monitored biochemically beginning at least 6 weeks after in those receiving recommended doses. These laboratory
starting therapy. Thyroid function should be assessed every findings indicate overtreatment and dose reduction since there
6-8 weeks until the patient is euthyroid and then rechecked is evidence of long-term cardiovascular risk linked to mild
annually, aiming to maintain T4 and TSH within the normal overtreatment (180).
range. However, serum thyroid hormone levels normalize
before serum TSH. Serum thyroid hormone concentrations Undertreatment occurs more often than overtreatment. With
increase first, then the TSH secretion falls because of the evidence suggesting that up to 25 percent of patients receiving
negative feedback action of levothyroxine on the pituitary and L-thyroxine for hypothyroidism being under-treated, yearly
hypothalamus. measurements of serum TSH may be valuable in assessing
the adequacy of therapy and compliance. Patients who do not
Page 40 Nursing.EliteCME.com
adhere to the recommended therapy and take L-thyroxine a few In most patients, dose adjustments for L-thyroxine are often
days before a clinic visit will have normal or even elevated T4 not required, with pregnancy being an exception. In the latter,
levels with paradoxically raised TSH (180). dose increments are required in order to maintain serum
TSH levels. Therapy with some drugs such as rifampicin,
Patients with symptoms such as unrelenting tiredness, phenytoin, carbamazepine (increased clearance of thyroxine)
somnolence, or slight cognitive problems like forgetfulness may and cholestyramine, sucralfate, aluminium hydroxide,
have their doses increased by 25 μg daily or on alternate days. ferrous sulphate (reduced absorption of thyroxine) also alters
L-thyroxine dose requirements because of their effects on its
If the initial diagnosis of hypothyroidism is still in question
absorption or metabolism.
once L-thyroxine treatment has been started, the clinician may
opt to stop treatment for 6 weeks and measuring serum TSH Generally, TSH suppression is not a desirable outcome because
and T4 in the untreated patient. of its potential adverse effects on cardiac function like cardiac
hypertrophy, atrial fibrillation and bone metabolism (180).
Nursing.EliteCME.com Page 41
Radioactive iodine ablation
Ablation of the gland happens during 2-5 months following level). Several weeks after131 I therapy, patients can, in rare
radioactive iodine therapy, at which time, many patients cases, become thyrotoxic as a result of extensive and successive
become hypothyroid. Checking thyroid functions every thyroid destruction and release of preformed hormone. It
4-6 weeks until the patient has stable thyroid functions is usually occurs with a painful, radiation-induced thyroiditis
recommended. that can be treated with nonsteroidal anti-inflammatory drugs
(NSAIDs) or glucocorticoids. Furthermore, radioactive iodine
After stable thyroid functions have been established, a partial ablation can lead to the secretion of thyroid antigens and
or low-dose thyroid hormone replacement is recommended aggravate the autoimmune thyroid disease process (e.g. Graves
(50-75 µg/day, adjusted every 6-8 weeks to normalize the TSH disease worsening) (181).
Thyroid surgery
Routine check ups following thyroid surgery may be needed After subtotal thyroidectomy for hyperthyroidism and
because of the possible development of hypothyroidism (from discontinuation of anti-thyroid therapy, many patients develop
chronic thyroiditis), recurrent hyperthyroidism, or eye disorders hypothyroidism, depending on how much functional thyroid
at some point in the future. The majority of patients remain tissue is left by the surgeon. A partial hormonal replacement
euthyroid after a lobectomy or lobectomy plus isthmusectomy therapy with L-thyroxine is recommended immediately
to treat a toxic adenoma or toxic multinodular goiter with a after surgery, usually at doses 50-75 µg/day. Postoperative
dominant nodule. To make sure that normal thyroid function thyroid function tests should be taken after 4-8 weeks, and the
has been firmly re-established, thyroid function tests should be L-thyroxine dose adjusted according to TSH levels (181).
obtained 3-4 weeks after a lobectomy.
Comorbidities
Comorbidities adversely affect patients with compromised ●● Response to therapy
thyroid function in several ways, namely; ●● Proper evaluation of associated illness
●● Overall prognosis
Diabetes Mellitus
Approximately 10 percent of patients with diagnosed type 1 (182). In clinical practice, the existence of hyperthyroidism and
diabetes mellitus ultimately develop chronic thyroiditis in their diabetes has several implications, namely (182);
lifetime, which may include the insidious onset of subclinical ●● Cautious diagnosis of glucose intolerance needs to be kept
hypothyroidism. Patients with diabetes should be examined in mind since elevated blood sugar level may improve with
for the possibility of goiter. Patients with one organ-specific treatment of thyrotoxicosis.
autoimmune disease (e.g. thyroid disease) are at greater risk of ●● Hyperthyroidism should be considered in diabetic patients
developing other autoimmune disorders; it is not uncommon with unexplained high blood sugar levels.
that 30% of women with diagnosed type 1 diabetes also have a ●● Anticipate worsening of glycemic control in diabetic
coexisting thyroid disease. A number of studies have found that patients with hyperthyroidism and adjust treatment
a higher than normal prevalence of hypothyroidism in type 2 accordingly. Recovery to euthyroid state will subsequently
diabetic patients (182). result in better glycemic control.
Thyroid dysfunction adversely affects diabetes control. In hypothyroidism, the decreased rate of the breakdown
Hyperthyroidism is mainly linked to poor glycemic control and of insulin may also reduce the insulin dose requirement.
elevated insulin requirements. Additionally, overstimulation The presence of hypoglycemia is uncommon in isolated
of hepatic gluconeogenesis, fast glucose absorption in the thyroid hormone deficiency and should be suspected of
GIT, and even increased insulin resistance may be observed. diminished pituitary function in a patient with underactive
Moreover, thyroid overactivity may unmask latent diabetes thyroid function. Moreover, hypothyroidism usually coexists
with various abnormalities in plasma lipid metabolism,
Page 42 Nursing.EliteCME.com
including elevated LDL concentrations. Even subclinical thyroid-stimulating hormone (TSH) 17 months following
hypothyroidism can worsen hyperlipidemia in patients with delivery. Fluctuating glycemic control during transient
type 2 diabetes and magnify the risk of heart diseases. The hyperthyroidism succeeded by hypothyroidism is a typical
administration of thyroxine hormone replacement usually clinical picture of postpartum thyroiditis. Recurrent thyroiditis
normalizes the lipid dysfunction (182). with later pregnancies is common (182).
Transient thyroid dysfunction is not uncommon in postpartum Sensitive TSH measurements should be obtained at regular
women with type 1 diabetes, representing approximately 25% intervals in patients with diabetes, especially if a goiter
of diagnosed cases. It requires routine screening with serum develops or if evidence is found of other autoimmune disorders.
Infertility
Some patients with infertility and menstrual irregularities have than hypothyroidism. Chronic thyroiditis can be identified by
underlying chronic thyroiditis in conjunction with subclinical or a careful, comprehensive history, physical examination, and
clinical hypothyroidism. Typically, these patients seek medical appropriate laboratory evaluation.
attention because of infertility or a previous miscarriage, rather
Depression
The diagnosis of subclinical or clinical hypothyroidism conversion of T4 into active T3 in the brain. T3 was suggested
must be considered in every patient with depression. In to enhance neurotransmission in the central noradrenergic
fact, a small proportion of all patients with depression have pathways (185).
primary hypothyroidism either overt or subclinical. Moreover,
all patients receiving lithium therapy require periodic According to the American Association of Clinical
thyroid evaluation because lithium may induce goiter and Endocrinologists (AACE), “the diagnosis of subclinical or
hypothyroidism. clinical hypothyroidism must be considered in every patient
with depression” (186). Of the variety of neuropsychiatric
Studies found that tricyclic antidepressants (183) and SSRIs manifestations of thyroid disorders, depression remains the
(184) enhance the activity of D2 resulting in an increased most common (187).
Thyroid cancer
A population-based observational study by Kuijpens et al. geriatric syndromes such as weakness, urinary incontinence,
found that prior diagnosis of hypertension was associated with malnutrition, depression, and balance disorders.
thyroid cancer. Additionally, a history of external radiation for
diagnostic and therapeutic procedures for tuberculosis has been Cancer diagnosis in older patients is likely to be made in the
suspected as the possible explanation for the high prevalence context of the patient’s pre-existing health problems which are
of former tuberculosis in the elderly thyroid cancer patients. very important issues in making clinical decisions concerning
Apparently, treatment choices are influenced by the existing treatment.
patient comorbidities. It did not, however, affect survival up to
Evaluation of existing comorbidities, specifically the severity,
5 years; a study with a longer period of follow-up is required
overall and individual impact on the cancer course in older
(188).
patients newly diagnosed with cancer are vital to the provision
Elderly patients are more prone to have serious medical of optimal cancer care and improved prognosis. Specifically,
conditions associated with thyroid cancer which include appropriate and careful assessments of these comorbidities
hypertension, cardiac disease, cardiopulmonary disease, improve the diagnostic acumen of clinicians thus, enhancing
tuberculosis, arthritis, COPD, other malignant tumors, patient therapeutic outcomes, survival, recurrence prevention,
diabetes mellitus and stroke. Older individuals may also have limitation of deterioration and/or complications, and
symptomatic relief.
Concomitant therapy
Thyroid diseases are usually managed with monotherapy of Another exception to monotherapy is in cases where there
hormones or anti-thyroid drugs. There are a few exceptions to are adrenergic symptoms to be addressed such as in overt
this; one of which is thyroid cancer, wherein a more aggressive hyperthyroidism. Many of the clinical manifestations of
approach to treatment is necessary to achieve favourable hyperthyroidism are caused by adrenergic overstimulation
prognosis. For example, concomitant use of docetaxel with resulting from over-expression of beta-adrenergic receptors and
radiation is highly effective in the treatment of anaplastic beta-receptor stimulation. These symptoms include palpitations,
thyroid cancer. The promising results warrant a phase 2 study to anxiety, tremors, and sensitivity to heat. Adrenergic blockers,
fully explore the potential of this combination (189). or beta blockers, are given to address such symptoms. The
beta blocker, propranolol, has become the drug of choice
Nursing.EliteCME.com Page 43
because most of these effects are mediated by beta-receptors. Other drugs such as reserpine and guanethidine, both depletors
Furthermore, it has fewer associated adverse effects. Some of catecholamines, clonidine, and calcium channel blockers
reports suggest that propranolol decreases T3 plasma levels decrease the adrenergic symptoms of thyrotoxicosis. Calcium
by blocking the peripheral deiodination of T4. Initial doses of channel blockers such as diltiazem and verapamil are used
20-40 mg of propranolol four times daily are typically effective especially when there is contraindication to beta-blockers.
to maintain the heart rate below 100 beats/min. Young patients Diltiazem 120 mg every eight hours is effective to reduce the
and those with more severe symptoms may require higher heart rate.
doses. Contraindications to beta-blockers are congestive heart
failure, cardiomyopathy, sinus bradycardia, asthma, and COPD.
Alternative therapy
Ayurveda to treat thyroid disorders. In case of hyperthyroidism, the herb
Ayurvedic therapy is based on the doctrine that certain Kaishore Guggulu is used to reduce “pitta”. Emphasis is also
substances from vegetable, animal and mineral origins have given on herbs that contain iodine and those that promote
curative values. The fundamental principle of ayurveda is that thyroid function and boost immunity (190).
all diseases in the body originate from the imbalance of “vatta”,
“pitta” and “kapha”. Goiter can also be reduced by the consumption of milk and
milk products, rice, barley, lentils, Bengal gram and sugarcane
According to Ayurvedic principles, there are many herbs that juice. Pistia, a common weed found nearby rivers and lakes, is
can help in thyroid disease. “Kanchanara Guggulu” is the most applied to the thyroid gland to reduce its swelling (190).
potent herbal formula listed in the Indian pharmacopoeia for
treating all types of thyroid disorders. It is known to remove Ayurveda also advocates “yoga” and “Pranayama” to support
dormant “kapha” from the body. It also removes toxins from the thyroid functioning. Yoga promotes inner peace and Yogic
lymphatic system. Other Ayurvedic herbs like Triphala, Shilajit, postures like neck rotation, neck extensions and shoulder stands
Punarnava, Gokshura and Brahmi are combined in many ways are believed to improve thyroid function and metabolism.
Homeopathy
Homeopathy is a system of drug therapeutics based on the only natural substances and natural processes to prepare its
“law of similar”. For example, a drug or substance that causes remedies. There are more than fifty homeopathic remedies
the symptoms of a disease in healthy people will cure similar for thyroid disorders. The reason for multiple remedies is the
symptoms in sick people provided that it is homeopathically fact that selection of homeopathic remedies is based on the
potentized. Homeopathy offers a holistic approach; instead of personality and constitution of an individual. Homeopathic
focusing on the thyroid disease, it considers the patient as a medications reportedly have no side effects and can be taken
“person” which includes taking into consideration the overall with multiple medications (191).
personality before prescribing a medicine. Homeopathy uses
Naturopathy
Naturopathy focuses on the healing powers within the body Treatment for thyroid disorders consists of natural therapies
itself. Its principles revolve around the idea that every such as dietary modifications, lifestyle modifications, herbal
human being has healing powers; the immune system is an supplements, minerals and vitamin supplements, acupuncture,
integral part of it which maintains equilibrium. Naturopathy hydrotherapy and massage in order to treat the underlying cause
believes that disease results from a hectic lifestyle and poor of the problem and re-establish the balance of the endocrine
eating habits that result in elevated stress levels that create system, thereby, improving thyroid functions (193).
unevenness and disorders within the body that in turn, affects
its vital energy supply (193).
Page 44 Nursing.EliteCME.com
NEW ADVANCEMENTS
Diagnostic techniques
Ultrasound guided fine-needle biopsy US-FNAB yield portion of the nodule, thereby, reducing the chances of
The use of fine-needle aspiration biopsy (FNAB) is the indeterminate results due to lack of thyroid cell sample. Needle
conventional method of detecting cancerous cells in thyroid biopsy produces indeterminate results in 75 percent of cases,
nodules, but it comes with pitfalls, namely; it lacks adequate with the other 25 percent classified as suspicious of carcinoma.
sensitivity and specificity. About one-quarter of suspicious results are eventually
diagnosed as thyroid cancer (194).
When FNAB is performed under ultrasound guidance, it
is capable of obtaining aspirate sample from the highest-
Treatment strategies
Multikinase inhibitors
The multikinase inhibitors discussed below are oral novel of axitinib in any type of metastatic thyroid carcinoma, with
agents currently being studied for their therapeutic efficacy in partial remission in 30 percent of the patients (199).
various forms of advanced thyroid carcinoma.
The second agent is motesanib which targets the VEGFR
The first agent is axitinib which effectively inhibits all of the 1–3, RET and c-KIT. During the first stage of its clinical trial,
VEGFRs. One of five patients with thyroid carcinoma included a 50 percent overall response rate was seen in patients with
in the first phase of clinical trial exhibited tumor shrinkage. advanced thyroid carcinoma. Based on these promising results,
The second stage of the clinical II trial showed the efficacy a multicenter second stage clinical trial was started to test its
efficacy in patients with progressive differentiated thyroid
Nursing.EliteCME.com Page 45
carcinoma and progressive or symptomatic medullary thyroid The summary of the revised recommendations are discussed in
carcinoma (200). detail below (224):
The third agent is vandetanib which targets VEGFR 2 and 3, Radiation safety officer: All treatments should be provided by a
RET and EGFR. Vandetanib effectively inhibits RET/PTC3 clinician trained in the administration of radiopharmaceuticals,
chromosomal translocations found in some PTC and M918T under safety precautions/protocols determined by the radiation
RET mutations occurring in MEN2B-associated and certain safety officer. The radiation safety officer should also develop
medullary thyroid carcinoma. Currently, it is in the second patient-specific precautions, taking into account the predicted
stage of clinical trial, its efficacy being studied in patients retained radioactivity in each patient.
with metastatic hereditary forms of medullary thyroid
carcinoma (201). Pregnancy/reproduction: Women from the age of menarche to
2 years after menopause should be tested for pregnancy, and
The fourth agent is sorafenib which targets BRAF, VEGFR 1 should be informed that pregnancy is a contraindication to I131
and 2 and RET, conducting proapoptotic and antiangiogenic therapy. Women should avoid becoming pregnant for 6 months
actions. During its second stage of clinical trial, researchers after treatment to allow for the normalization of thyroid levels.
found a partial remission rate of 23 percent and a stable disease Men should be advised that fathering a child within 3 months
rate of 53% in mainly patients with advanced differentiated of radiation exposure has not been associated with an increase
thyroid carcinoma (202). in congenital abnormalities or fetal demise. They should be
advised, however, that full fertility may not return for 1 year,
The last agent is sunitinib which targets VEGFR 1–3, RET and that they should not attempt to produce a pregnancy until at
and RET/PTC subtypes 1 and 3. A response rate of 8 percent least 3 months after the completion of I131 therapy.
in differentiated thyroid carcinoma patients and 13 percent in
medullary thyroid carcinoma patients was reported during a Breastfeeding: Breastfeeding should be discontinued because of
phase II trial to determine the effect of sunitinib in refractory the risk to the infant related to exposure during lactation.
advanced thyroid carcinoma. Furthermore, 67 percent of
differentiated thyroid carcinoma patients and 87 percent Dose rate calculations to determine distance: When exposure
of medullary thyroid carcinoma patients showed disease from a treated patient at 1 meter (3.2 feet) exceeds the NRC-
stabilization (203). defined regulatory limit of less than 7 millirem/hour, people
should remain at least 6 feet (1.8 meter) away, although adults
Latest recommendations on the radiation safety after treatment can be within 1 meter of the patient for brief periods, “preferably
with radioiodine I-131 by the American Thyroid Association only for minutes.” Patients should drive alone or, when riding in
(ATA), 2011 a car, stay as far away from other occupants as possible.
The task force created by the American Thyroid Association to Travel through ports of entry: For 4 months after therapy,
develop radiation safety recommendations for the information patients crossing borders (via airports, tunnels, or bridges)
and guidance of medical professionals, patients and family should carry a form specifying the date of treatment,
members. The recommendations, which are compliant with the radionuclide used, and provider contact information.
Nuclear Regulatory Commission regulations and consistent
with guidelines promulgated by the National Council on Post-treatment accommodations: Patients should not stay in
Radiation Protection and Measurement (NCRP-155), can hotels, should avoid public transportation, and should avoid
help physicians and their patients keep radiation safety post- being in close proximity to others.
treatment with I-131. Both clinicians and patients need to be
Personal hygiene: Patients should use special precautions,
informed of these guidelines in order to attain optimal safety.
especially during the first 48 hours, to minimize the possibility
In 2011, stricter precautions were set in order to limit the of exposing others to urine, stool, saliva, blood or bodily
radiation exposure to family members, fetuses, children, fluids, perspiration, or vomit. Specialized leak-proof waste
caregivers and the general public from patients recently treated disposal bags should be made available to the patient during the
with radioiodine. restricted period.
PATIENT EDUCATION
Patient education is very important, but at times, a difficult matter Generally, the patient should be educated thoroughly regarding
to address. Many clinicians believe that patient education is an the following points:
indivisible part of the management of any disease.
1.The basic information about thyroid disease
Patient education results in better treatment compliance and The patient should be informed about the diagnosis. After
more successful treatment outcomes. But many doctors find experiencing the abnormal symptoms, the patient will
it difficult too. It is the equal responsibility of the other health appreciate basic information about the disease. Knowledge
care practitioners such as nurses, physician’s assistants, and is power and for some patients, it is also a relief to finally
pharmacists to educate patients and answer their questions know the cause of their suffering. The use of patient-friendly
whenever the situation calls for it or the need arises (204).
Page 46 Nursing.EliteCME.com
language and lesser medical jargon makes way for better patient The patient with hypothyroidism who is currently on thyroid
understanding and faster communication. hormone replacement therapy should be advised to take the
hormonal pill on an empty stomach. Additionally, they should
2. Nature of the disease be advised to regulate their intake of dietary fibers as they
The patient should be educated regarding the nature of their impair the absorption of synthetic thyroid hormones. There are
disease. They need to understand the nature of their symptoms some foods, medications and supplements which exert a similar
and how they can best manage it. Additionally, they should be type of effect on the gastrointestinal system and should likewise
informed about their chances of recovery (prognosis). be avoided by the patient.
3. Duration and type of treatment Patients on hormone replacement therapy should avoid taking
Since most thyroid dysfunctions are chronic in nature, they their thyroid hormone at the same time as:
need to understand that treatment and management are long ●● Walnuts
term and requires regular follow up. This is very important ●● Soybean flour
because patient adherence is often difficult in the long run. ●● Meal containing cottonseeds
Many patients stop their medication and follow up check ups ●● Iron supplements or multivitamins containing iron
after a few months of treatment because of the initial relief ●● Supplements of certain minerals like calcium, iron or
of the symptoms. Abrupt cessation of therapy has deleterious multivitamins containing iron
consequences; many patients who experienced relapse ended up ●● Aluminium or magnesium containing antacids
with a more severe form of the disease that is difficult to control ●● Medications like sucralfate (used for the treatment of ulcer)
and stabilize. ●● Some anti cholesterol drugs like cholestyramine and
colestipol
Additionally, hormone replacement is a key part of therapy for
many hypothyroid conditions; patients need to know in advance To avoid unwanted interactions with these medications, patients
the side effects to expect from the synthetic hormones. should eat or take them several hours before or after taking the
prescribed synthetic hormone.
4. Dietary advice
Nutrition plays an important role in maintaining healthy thyroid 5. Vitamin and mineral supplementation
function. Following a healthy and balanced diet is a good step It is medically advised that every patient with hyperthyroidism
towards the right direction. It helps avoid unwanted weight should be supplemented with multivitamins as to overcome the
gain, metabolic imbalance and musculoskeletal symptoms. extra demand of the body especially vitamin A and C as well
Research is in favor of food intake which improves thyroid as riboflavin, thiamine, B6 and B12. A number of studies have
function and restores metabolism. A diet rich in organic food, found that up to 30% of people with advanced thyroid disease
citrus foods, sea foods, and the so called “good” oils such as experience a vitamin B12 deficiency. As a result, patients
extra virgin olive oil helps improve thyroid functions. Ideally, should try to incorporate food sources rich in vitamin B12
fruits and vegetables such as carrots, spinach, olive oil, such as mollusks, sardines, salmon, organ meats such as liver,
avocados, asparagus, whole-grain cereals, bananas and oily muscle meat, and dairy. Untreated vitamin B12 deficiency can
fishes should also be included. lead to irreversible damage, which is why it’s imperative for
clinicians to recommend patients with thyroid disease to have
The patient with hyperthyroidism should avoid stimulants
their levels tested (210).
like caffeine and also food with natural goitrogenic properties
such as cabbage, broccoli, sweet potatoes, lima beans and soy Patients with hypothyroidism can also benefit from selenium
products. These foods interfere with iodine uptake and disrupt and zinc supplementation. Following thyroidectomy, patient
thyroid function (205). should be advised to take calcium supplementation without fail.
Selenium-rich foods
Selenium is an element which plays a role in the hormonal and sesame seeds are rich in selenium. Regular intake of these
balance of thyroid hormones. Foods such as mushrooms, garlic, foods may prevent thyroid dysfunctions (205).
onions, eggs, beef liver, shellfish, wheat germ, sunflower seeds,
Iodine
Patient should be educated regarding the role of iodine in the is important to include them in the diet and that the main source
maintenance of thyroid functions. They should be informed that depends on dietary or supplementary intake.
the body does not produce endogenous iodine which is why it
Vitamin D
A study by Tamer et al. have found an association between the causal relationship, if any exists, between the two remains
vitamin D deficiency and Hashimoto’s thyroiditis, with more unclear (206).
than 90 percent of the study patients being deficient. However,
Nursing.EliteCME.com Page 47
Hyperthyroidism, specifically Graves disease, causes from sleeplessness, low energy level and mood swings which
bone density loss which can be aggravated by vitamin D are all minimized by regular exercise.
deficiency. Bone mass may be recovered with subsequent
therapy for hyperthyroidism with sufficient intake or adequate A study by Cutovic et al. found that a structured exercise
supplementation of bone-building nutrients, such as vitamin D, regimen exhibited dramatic improvements in fatigue levels,
which are important during and after treatment. with more patients being able to successfully stop taking anti-
thyroid medications without a relapse (208).
Recommended foods for vitamin D intake are fatty fish, milk,
dairy, eggs, and mushrooms. Patients with vitamin D deficiency 7. Eye care and skin care
may need supplemental vitamin D3 (206). Patients with Graves disease usually have ophthalmopathy. They
should be advised to use cold compresses to their eye area to
6. Exercise relieve the pain. Additionally, they should learn to protect the
Studies have proven that following a regular exercise plan or protruded eyes from harmful UV rays, sunlight and wind through
regular sports activity compliments medical therapy in thyroid the use of protective eyewear such as sunglasses. Additionally,
patients. The exercise is a “natural antidote” to the symptoms patients may require eye drops to help relieve eye dryness.
of thyroid disorders like weight gain, muscle loss, low energy, Elevation of the bed also helps relieve growing eye pressure.
depression, and mood swings.
The severity of the ophthalmic symptoms is not related to the
Patients with hypothyroidism can benefit from regular exercise. severity of the hyperthyroidism. Severity of the symptoms
It improves metabolism and replaces fat with lean muscle mass. are seen more in patients with Graves’ disease who smoke
On the other hand, patients with hyperthyroidism often suffer cigarettes (209).
Page 48 Nursing.EliteCME.com
subclinical hypothyroidism. If detected, another form of 3. Tertiary prevention refers to the avoidance of disease
secondary prevention is warranted in the form of treatment with progression. It entails frequent and regular clinical and
thyroxine to prevent further thyroid failure. laboratory assessments. A good example is the prevention of
thyroid hormone overdose.
CONCLUSION
There is a considerably high prevalence of thyroid diseases come in contact with those who recently received it. Recent
among the American population, with approximately 20 million advances have made thyroidectomy a straightforward operation,
having one form or another. The American Thyroid Association requiring minimal incision and reduced recovery period. It
estimates that sixty percent of this number are unaware of their has minimal risks. Furthermore, adjuvant therapy to address
condition, the majority of which are women, especially elderly symptomatic complaints associated with thyroid dysfunction is
ones. The most diagnosed forms are of autoimmune origins, widely used in conjunction with the standard treatments.
Graves disease and Hashimoto’s thyroiditis. Thyroid cancers
and iodine-deficiency goiters are rare. The diagnosis of thyroid diseases, especially those with
suspected and non-determinate FNAB samples have been
Despite the prevalence and healthcare costs associated with further advanced with the help of ultrasound technology.
their complications, adult-based population screening measures Thyroid function tests have been and still are the primary
have been recommended, but general consensus as to the exact tests to determine the functional status of the thyroid gland.
guidelines remain elusive with various health and federal Despite its several pitfalls, TSH screening test remains the
organizations undecided and conflicted on the issue. gold standard in the initial evaluation of the root cause of the
thyroidal symptoms. The popularity of alternative therapy in the
Thyroid diseases generally present a positive clinical outlook last decade has also made it a logical choice for many patients.
once therapy is established and maintained. The exception These include Ayurveda, homeopathy and naturopathy.
to this is thyroid cancer, with anaplastic carcinoma offering
the poorest prognosis. Thyroid diseases mostly present with The growing advocacy of patient involvement in all aspects
general and nonspecific symptoms, resulting in delayed of the treatment process has made patient education an
diagnosis. Hypothyroidism is commonly addressed with indispensable part of patient-clinician relationships. Ideally,
hormone replacement therapy with the drug L-thyroxine, while patients need to be aware of their diagnosis, the treatment
hyperthyroidism is usually treated with the anti-thyroid drugs, required and their role in it, especially adherence to the
propylthiouracil and methimazole. Propylthiouracil is the prescribed therapy. The likelihood of relapse due to abrupt
drug of choice in pregnant women. Thyroid disorders during discontinuation of therapy is increased in patients who are not
pregnancy pose serious risks to both the mother and the baby, aware of the consequences of such actions.
thus, requiring immediate management and careful monitoring
throughout the gestational period and after delivery. Last but not the least, a number of studies has shown various
risk factors to thyroid diseases. Although not always backed
Severe and unrelenting forms of thyroid diseases are addressed by concrete evidence, the knowledge of such factors may
with radioactive iodine therapy and thyroidectomy. Radioactive ultimately lead to well-informed decisions by patients that
iodine therapy makes use of ionizing radiation which presents a subsequently result in better health and therapy outcomes.
risk of unnecessary post-treatment exposure to individuals who
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Thyroid Disorders
Final Examination Questions
Choose True of False for questions 1 through 10 and mark your answers online at Nursing.EliteCME.com
1. Goiter refers to the enlargement of the parathyroid glands. 6. Toxic adenoma refers to the malignant monoclonal nodular
¨¨ True growth which results in autonomous hyperfunctioning of
follicular thyroid cells.
¨¨ False
¨¨ True
2. The incidence of thyroid diseases is higher among the male ¨¨ False
geriatric population. 7. The antiarrhythmic drug amiodarone is rich in iodine
¨¨ True and structurally resembles the thyroid hormone, T4, and
stimulates its receptors.
¨¨ False
¨¨ True
3. Thyroid hormones stimulate bone turnover leading to ¨¨ False
osteopenia in long-standing hyperthyroid condition. 8. Follicular thyroid carcinoma is the most aggressive form of
¨¨ True all thyroid malignancies.
¨¨ False ¨¨ True
¨¨ False
4. De Quervain’s thyroiditis is a malignant type of thyroid 9. Thiocyanate inhibits iodide transport potently. There are
disease. two proposed actions of thiocyanate on the thyroid gland.
¨¨ True ¨¨ True
¨¨ False ¨¨ False
10. Gestation hyperthyroidism is characterized by the presence
5. Graves disease is the leading cause of hyperthyroidism in of antimicrosomal antibodies and manifests clinically
the US. as transient thyrotoxicosis, hypothyroidism, or transient
¨¨ True thyrotoxicosis followed by hypothyroidism.
¨¨ False ¨¨ True
¨¨ False
NMA13TDI15
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