Endocrinology (Abduraji,Anfone)

Body functions are regulated by 2 major control

systems:
1.
Nervous system:
a. Exerts point-to-point control through
nerves.
b. Nervous control is electrical in nature.
c. It is fast.
2.

Hormonal, or endocrine system:

A group of glands which have NO ducts.
Secrete their hormones into blood & extracellular
fluid.
Most hormones circulate in blood, & come in
contact with essentially all cells.
A given hormone usually affects only a limited
number of cells, called target cells.
Target cell responds in specific way to a hormone
as it bears specific receptor proteins for the
hormone.
A cell is a target because is has a specific receptor
for the hormone.
Hormonal Interactions:
v Synergistic: Two hormones work together to
produce a result.
v Additive: Each hormone separately produces
response, together at same concentrations
stimulate even greater effect.
NE and Epi.
v Complementary: Each hormone stimulates
different step in the process. FSH and
testosterone.
Distance between hormone producer cell &
hormone responder cell may be large,
moderate, or small. Generally, act slower in onset,
more prolonged, & more diffuse than NS. Under
control of NS.
Maintenance of internal environment
(homeostasis).
Regulation total body metabolism.
Control of energy production, utilization &
storage.
Integration & regulation of growth &
development.
Control, & maintenance of sexual reproduction,
including gametogenesis, fertilization, fetal
growth & development & nourishment of the
newborn.
bodys response to environmental stimuli.
Hormones & hormone-like substances are also
produced by other organs in the body that serve
other functions as well; such as:

Heart Atrial natriuretic peptide (ANP)

Liver Somatomedins (insulin-like growth
factors IGF-1)
Adipose tissue Leptin
kidneys Erythropoietin

A hormone is a chemical substance that is

secreted into the blood by one cell or a group of
cells & exerts a physiological control & regulatory
effect on other cells of body.
Onset & effect of hormone secretion:
Each hormone has its own onset & duration
of action; e.g.
Catecholamine: secreted in sec, & its full action
(sec - min.)
Aldosterone: ? takes 1hr to act.
Thyroxine; GH: ? require months for full effect.
Types of hormones:
1) Local hormones- Ach,Secretin
,Cholecytokinin
2) General hormones
Catecholamines,GH,TH
3) Target tissues hormonesACTH,Ovarian
hormones,Oxytocin
Types of hormones:
II: According to Chemical classification
Hormones are categorized into 4 structural
groups, with members of each group having many
properties in common:
Peptides and proteins
Amino acid derivatives
Steroids
Fatty acid derivatives - Eicosanoids
Classification :
Tissue Origin
Structure
Tissue origin
Hypothalamus-Thyrotropin-releasin hormone,
Corticotropin-releasing factor, other releasing
factors
Anterior Pituitary- Thyroid-stimulating
hormone, adenocorticotropic hormone (ACTH),

follicle-stimulating hormone, leutenizing

hormone, prolactin, Growth hormone
Posterior Pituitary-Vasopressin, Oxytocin
Adrenal medulla- Epinephrine, norepinephrine
Adrenal cortex-Cortisol, aldosterone, 11deoxycortiso
Thyroid- Triiodothyronine, thyroxine, calcitonin
Parathyroid- Parathyroid hormone
Pancreas- Insulin, glucagon
Gastrointestinal Tract- Gastrin, others
Ovaries- Estrogen, progesterone
Placenta- Progesterone, human chorionic
gonadotropin, human placental lactogen
Testes-Testosterone, other androgens
Kidneys-1,25-(OH)2 vitamin D, erythropoietin
Unknown- Prostaglandins
Classification by structure:
Peptide hormones- releasing factors,
water soluble and do not require
transport proteins
Steroid hormones- regulation of sexual
development and characteristics.
Synthesized from cholesterol as basic
molecule. Not water soluble, require
transport protein. Synthesized in the
adrenal gland, gonads or placenta.
Amino acid derivatives- properties
similar to both steroid and peptide.
Fatty acid derivatives- include
prostaglandins
Adrenal glands
1. Adrenal endocrine function includes
regulation of proteins, carbohydrates and
many metabolic function.
a. Glucocorticoid (steroid) produced in
zona fasciculata and reticularis or a.
cortex
catabolized in liver and kidneys,
regulated by hypothalamus- pituitary-adrenal
axis.
promotes breakdown of protein and
lipid, inhibiting protein synthesis.

Cortisol CHO, lipid, protein

metabolism; suppression of
inflammation; stimulating
gluconeogenesis; increasing urine
production; stimulating erythropoiesis
Target tissue : kidney glomerulus and
renal tubules, bone marrow stem cell,
hepatocytes, adipose tissue
B. Mineral corticosteroid synthesized from
cholesterol. Primary action is regulation of
electrolytes.
1. Aldosterone
- stimulates sodium resorption in the
distal convoluted tubules in exchange for
potassium or hydrogen

- increase blood volume and pressure

- regulate extracellular fluid volume
Target tissue: distal renal tubules and large
intestine
2. Catecholamine are products of
hydroxylation of the amino acid tyrosine.
- mobilization of energy stores by
increasing blood pressure, heart rate, blood
sugar level ( glycogenolysis)
-neurotransmitter actions
-released in response to pain and
emotional distress to mobilize organs
Tissue target : liver and adipose tissue
approx. 20% excreted in urine as
metanephrine and normetanephrine
Approx. 80% converted to
vanillylmandelic acid (VMA)
Diseases:
Hyperadrenalism
1. Cushings syndrome: excess cortisol
production, either of the adrenal gland
or increased relase of ACTH
2. Hyperaldosteronism excess
aldosterone production with
hypertension symptoms.
Conns syndrome- induced by an
aldosterone-secreting adrenal adenoma or
adrenal hyperplasia
Excess renin production leads to
elevated aldosterone.
3. Congenital adrenal hyperplasiadeficiency of enzymes in synthetic pathway
that leads to cortisol and aldosterone
production. ACTH levels increased, steroid
hormones are hyper secreted. 21hydroxylase deficiency
Hypoadrenalism
1. Addisons disease
Pheochromocytoma- major disorder of the
adrenal medulla, hyper secretion of
catecholamines.

A Cortisol test may be used to help

diagnose Cushing syndrome, a
condition associated with excess
cortisol, or to help diagnose adrenal
insufficiency or Addison disease,
conditions associated with deficient
cortisol.
Dexamethasone suppression: The
dexamethasone suppression test
involves analysing a baseline sample
for cortisol, then giving the person oral
dexamethasone (a synthetic
glucocorticoid) and measuring cortisol
levels in subsequent timed samples.

Dexamethasone suppresses ACTH

production and should decrease
cortisol production if the source of the
excess is stress.
ACTH stimulation: This test involves
measuring the level of cortisol in a
person's blood before and after an
injection of synthetic ACTH. If the
adrenal glands are functioning
normally, then cortisol levels will rise
with the ACTH stimulation. If they are
damaged or not functioning properly,
then the cortisol level will be low. A
longer version of this test (1-3 days)
may be performed to help distinguish
between adrenal and pituitary
insufficiency.
The reference ranges for serum cortisol
are as follows:
Morning - 7-28 g/dL
Afternoon - 2-18 g/dL
Stimulated* - 18 g/dl
Suppressed** - < 2 g/dl
*Low-dose ACTH stimulation test: before or
after (anytime, but usually one hour) ACTH
250 g (one ampule) intravenous injection
**Overnight low-dose dexamethasone
suppression test: 8 AM serum cortisol after
oral dexamethasone 1 mg taken in late
evening (11 PM)

Thyroid gland
Thyroid hormones requires iodine for
synthesis. Iodine combines with thyroglobulin
to form hormone precursors.
98% of circulating T3 and T4 is bound
to protein, including thyroxine-binding
globulin (TBG) and thyroxine-binding
albumion.
Fxn : regulates carbohydrate, lipid and
protein metabolism. Acts on CNS,
stimulate the heart, and have a role in
physical growth and development.
Thyroid Disorders:
a. Hypothyroidism symtoms: enlarged
thyroid gland ( goiter), fatigue,
impaired mental process, loss of
appetite. Myxedema (loss of hair,
swelling of hands and face, coarse skin)
occurs as the disease progesses.
b. Primary Hypothyroidism caused by
damaged or surgically removed thyroid
gland.
c. Secondary hypothyroidism- decreased
production of TSH caused by pituitary

disorder leading to low serum level of

the hormone.
d. Tertiary hypothyroidism- hypothalamic
failure leading to lack of TRH
production.
b. Chronic immune thyroiditis (Hashimotos
disease)- genetic abnormality; massive
infiltration of thyroid glands by lymphocytes.
c. Hyperthyroidism also referred as
thyrotoxicosis
Symptoms: weight loss, loss of muscle mass,
hyperactivity yet, quick fatigability, insomia,
increased sweating, nervousness, palpitations,
goiter and bulging eyes.
Cause: pituitary tumor that cause excessive
TSH secretion, thyroid carcinoma, toxic
multinodular goiter (glands produces excess
hormones)
1. Graves disease: autoimmune,
immunoglobulins stimulate thyroid
gland by binding to TSH receptor.
2. Thyroiditis: inflammation of the thyroid
gland caused by either bacterial or viral
Assays:
1. T3 resin uptake analyzes capacity
of TBG to bind to thyroid
hormones.
2. Free thyroxine index (FT4I)
indirectly asseses the concentration of
circulating free T4.
3. Thyroid antibody screens: assays
for the presence of thyroid-stimulating
immunoglobulins, such as those in
Graves disease and Hashimotos
thyroiditis.
4. TRH stimulation test- measures
pituitary TSH stores and is conclusive
for hyperthyroidism. TRH is injected,
and blood samples are assayed for
TSH. TSH levels rise rapidly in a normal
person but will not rise in a
hyperthyroid patient.
Parathyroid Hormone-Produced by
parathyroid gland, which are small,
paired structures located posterior
thyroid capsule. Sole function for
production of parathyroid hormone.
Parathyroid hormone- synthesis begins with
the precursors.
a. Major physiologic action: mineral
homeostasis. Metabolism of both
calcium and phosphorus by the kidney
and bone.
interrelationships with vit. D , and calcitonin.
b. Transport. Transported freely circulating,
intact, active molecule.

PTH secretion rates:

1. Serum concentration of ionized calcium
2. Magnesium, which has an effect on PTH
that both parallels and modulates the
effect of calcium on PTH release
3. Biogenic amines like epinephrine,
dopamine, and serotonin.
4. Vitamin D
Calcium phosphorus metabolism
Calcium regulated by PTH and
vitamin D and calcitonin.
in bone: PTH increases bone
resorption of calcium in serum
In the kidney: PTH increases renal
reabsorption of calcium
Phosphorus- PTH lowers phosphorus
concentrations, whereas vitamin D acts
to increase blood phosphate.
Calcitonin- produced by parafollicular
cells in the thyroid. Decreases blood
calcium because of its effect on both
bone and renal calcium processing,
which is the opposite of PTH.
in bone: calcitonin inhibits bone
resorption of calcium
in the kidney: calcitonin decreases
the renal reabsorption of calcium, phosphorus,
sodium, potassium and magnesium.
Pathologic condition
Hypocalcemia: deficient PTH or vit. D
deficient state
1. Primary hypoparathyroidism
surgical removal of the parathyroid
glands, trauma following surgery or
radiotherapy directed to the thyroid
gland. Sx. Muscle spasm, skin drying,
brittle hair, hypotension, GI upset. Low
serum calcium and high phosphorus
2. Idiopathic hypoparathyroidismlow serum calcium and high
phosphorus level
3. Pseudohypoparathyroidism (PHP)lack of responsiveness to PTH by the
renal system or other organ system ,
not by a decrease in PTH. Serum PTH
are normal.

Hypercalcemia- serum calcium >102

mg/L . Sx. Can range from no symptom
to manifestations of polyuria,
polydypsia, kidney stone, nausea,
coma. Malignancy and
hyperparathyroidism account for most
cases of hypercalcemia.
1. Primary hyperparathyroidism:
parathyroid adenoma or hyperplasia.
Can be associated with other endocrine
disorders referred as multiple
endocrine neoplasia (MEN), which
involves pituitary, pancreas, thyroid
and adrenal gland. Serum calcium is
increased, PTH is increased and
phosphorus is normal to decreased.
2. Secondary hyperparathyroidism:
attempt of the body to compensate for
hypercalcemic states. Seen in patients
with renal failure who cannot excrete
phosphorus, resulting in decrease
calcium which stimulates PTH. Serum
calcium is low, PTH increased and
phosphorus is increased
Laboratory analysis
Primary analytes of interest calcium,
phosphorus and PTH.
1. PTH C-terminal analysis- examines
the intact PTH molecule and is highly
specific for detecting
hyperparathyroidism
2. PTH N-terminal analysis- measures
both the whole PTH molecule and the
amino-terminal fragments in serum
Additional analytes of secondary interest
includes calcitonin, vitamin D, magnesium,
bicarbonate and nephrogenous cyclic
adenosine monophosphate (cAMP).
Nephrogenous cAMP is under direct
influence of the PTH and is a measure of the
urinary portion of cAMP produced by the
kidneys and excreted in the renal tubules.

The reference range for PTH is as follows:

Normal - 10-65 pg/mL or 10-65 ng/L