HPI
14 yr old male presented to the RWJ ED with a
1 day history of headache, slurred speech, confusion, problems walking, and dizziness. Patient was in Gym class and experienced a sudden onset of these symptoms.
Headache-B/L temporal area, pounding in nature (-) photophobia/phonophibia Speech-inability of school nurse to understand him Walking- unable to walk in a straight line
Review of Systems
(+) 10 lb weight loss over an 8 month
period despite increased appetite (+) increased thirst (-) increased urine output (+) easy fatigability (+) tremors (+) increased watery stools
ROS cont.
(-) chest pain/palpitations (-) preceding behavioral changes (-) history of ingestion of any over the counter or prescription drugs or medications (-) exposure to carbon monoxide (-) trauma (-) fever (-) neck stiffness (-) night sweats
PMH
Born full term by normal delivery Diagnosed with ADHD as a child
Not treated with medications as patient able to function well in school without it. Normal baseline function
History cont.
Allergic to Penicillin : rash Immunizations: UTD Meds: MVIs Diet: Regular Family HX:
Mom GERD 16 yr old brother with eczema and ADHD (-) family hx of medical problems
plays basketball and baseball, attends 9th grade, (-) alcohol, illicit drug use, tobacco, denies sexual activity Development: appropriate
In the ED
Initial vitals:
T 99.2 HR 160 BP 145/84 RR 22 Sats 99% RA
Neck:
supple thyroid which was diffusely enlarged and firm to palpation, (-) bruit
Summary
14 yr old male without significant past medical
history who presents with sudden onset of headache, slurred speech, confusion, problems walking, and dizziness, Symptoms are associated clinically with tachycardia and hypertension on the background of an 8th month history of weight loss despite polyphagia, fatigue, and polydyspia.
Differential
Differential
Psyche
Neoplasm
Anxiety/panic attack ADHD Brain tumor Lymphoma TIA/Stroke Intracranial hemorrhage Meningitis/encephalitis Porphyria Concussion/increased ICP
Endocrine Hyperthyroidism DIABETES Pheochromocytoma Hypercalcemia Hypoglycemia Drug ingestion Cocaine Amphetamines Steroids Phenylepherine Ephedrine MAO Inhibiters PCP Mushrooms Lead poisoning Carbon monoxide poisoning
Neurologic
Diagnostic testing
Blood/urine:
CBC CMP ESR UA Urine Drug Screen Thyroid function studies (TFTs)
Radiology: EKG
Head CT
137
4.2
102 27.2
11 0.5
103 10.0
Prot: 6.1
Tbili 1.0
AST: 27 ALT:32
UDS: (-) barbiturates, Benzodiazepines, Cocaine , opiates, PCP, THC UA: 1.018, trace protein, (-) blood, nitrite, bilirubin, ketones ESR: 12
Differential
Psyche
Anxiety/panic attack ADHD Coarctation of the Aorta Arrhythmia Renal Artery Stenosis Polycystic kidney disease Glomerulonephritis Concussion/increased ICP TIA/Stroke Sub-dural hemorrhage Brain tumor Meningitis
Endocrine
Cardiac Renal
Trauma Neurologic
Other
Lead poisoning Carbon monoxide poisoning
Thyroid ultrasound:
Therapy initiated
Methimazole 10 mg bid Propanalol 10mg bid
Hyperthyroidism
Thyroid anatomy
Hyperthyroidism
Hyperthyroidism and thyrotoxicosis are used
synonymously However they refer to different aspects of the same condition as follows: Hyperthyroidism- BIOCHEMICALLY over activity of thyroid gland leading to excessive synthesis of thyroid hormones and accelerated metabolism in the peripheral tissues Thyrotoxicosis- CLINICALLY Clinical effects of unbound thyroid hormone whether to not the thyroid gland is the primary source
Pathophysiology
Controlled by a complex feed back mechanism The release of TSH from the anterior pituitary gland is stimulated by low circulating levels of thyroid hormones TSH is under the influence of thyrotropin-releasing hormone (TRH), somatostatin, or dopamine. TSH then binds to TSH receptors on the thyroid gland to release mostly t4 and some T3 Elevated levels of these T4 and T3 act on the hypothalamus and anterior pituitary decreasing synthesis of TSH.
TSH receptor
G-proteincoupled receptors. Large protein embedded in
the cell membrane. Contains an extracellular domain binds TSH and intracellular domain that acts via a G-protein second messenger system to activate thyroid adenyl cyclase, yielding cyclic adenosine monophosphate (cAMP).
Synthesis cont.
The result is the formation of monoiodotyrosine
(MIT) and diiodotyrosine (DIT). Coupling of MIT and DIT results in the formation of T3 and T4, which are then stored within the thyroglobulin in the extracellular thyroid follicular lumen. Unlike other endocrine glands, the thyroid has a large supply of stored preformed hormone.
Causes of Thyrotoxicosis
Graves Disease Chronic Lymphocytic Thyroditis (Hashimotos
Thyroditis) Toxic Adenoma McCune Albright Syndrome Subacute Viral Thyroditis TSH Secreting Pituitary Adenoma Exogenous Thyroid Hormone hCG Secreting Tumor
Toxic Adenoma
Autonomously functioning thyroid nodule
hypersecreting T3 and/or T4 resulting in thyrotoxicosis Aka Plummers disease Very rare in children Almost never malignant
Extremely rare
Occasionally T3 is ingested:
similar lab results but T4 is low
Graves Disease
Graves Disease
Most common cause of hyperthyroidism in
children accounts for >95% of childhood cases of hyperthyroidism Prevalence approximately 0.02% in childhood Gets it name from the Irish physician Robert Graves who described it in 1835.
Pathophysiology
Associated with HLA-B8 and HLA-DR3 haplotypes Polygenic inheritance The reasons for the development of Graves Disease are
presently unknown. Some postulated causes include:
Environmental Factors- damage to the thyroid, by radiation or ethanol injection, with liberation of antigens, has been noted, smoking also increases the risk Thymic Selection of Lymphocytes- pre-T lymphocytes may be educated in the thymus to recognize thyroid-related epitopes, and thus to generate self-tolerance against these thyroid-related antigens. Molecular Mimicry- exposure to a particular peptide epitope in an environmental antigen might develop immune reactivity to an amino acid sequence identical to that present in an human endogenous antigen such as TSH receptor, TPO, or TG. Thyroid Injury and Antigen Release- certain types of injury to the thyroid are followed by the development of thyroid autoimmunity, including Graves' disease. i.e. radiation
Pathophysiology cont.
Patients likely have defective immune tolerance, leading to
the development of specific auto antibodies directed against various thyroid antigens The TSH receptor is the most significant thyroid auto antigen in this disorder. However, children with Graves disease also produce immunoglobulin's directed against thyroperoxidase (anti-TPO) and thyroglobulin, as well as TSH receptorblocking antibodies
Demographics
Females affected more often than males
3-6:1 ratio Incidence increases throughout childhood with peak incidence in children 10-15 yrs No racial predilection seems to exist
Clinical
Children are usually identified because of
enlarged thyroid, weight loss or behavioral changes Exophthalmos less commonly observed in children Enlarged thyroid may cause dysphasia Symptoms may mimic ADHD
Symptoms
Dysphasia Irritability and emotional liability Sleeplessness and restlessness Inability to concentrate Deterioration of handwriting and school performance Frequent stools or diarrhea
Palpitations Pruritus Weight loss Increased appetite Nocturia, increase in urination and thirst Infrequent or light menses Weakness and tiredness Exercise intolerance Heat intolerance
The frequency of
signs :
Goiter (99%) Tachycardia (82%) Exophthalmos (47%) Tremor (61%) Thyroid bruit (53%) Increased pulse pressure (50%)
Physical
Patients can be thin
with a fixed stare and fidgety behavior Can see multiple ophthalmological, thyroidal, cardiopulmonary, neuromuscular and dermal findings.
Labs
Hyperthyroidism
confirmed simply and quickly with measurements of FT4 and TSH
Graves Disease
confirmed by measurement of TSH receptor stimulating immunoglobulins, i.e. TSIgs
Imaging
Diagnostic radioiodine I
131 uptake is rarely performed Either technetium Tc 99m or 123I scan may be useful if the gland does not have a uniform consistency Ultrasound may also be used to image the gland
Treatment
3 main treatments
Medical therapy Radio-iodine Ablation of the thyroid gland Surgery
Antithyroid drugs
2 main medications are used in the U.S.
Propylthiouracil and Methimazole Inhibit thyroid biosynthesis decreasing the oxidation of iodine and iodination of tyrosine. PTU diminishes the peripheral conversion of T4 to T3 PTU is required TID because of shorter half life Methimazole can be administered BID
Therapy cont.
Glucocorticoids
Decrease peripheral T 4to T 3conversion, and may have a more prolonged suppressive effect on thyrotoxicosis Prednisone has been reported to induce remission of Graves' disease, but at the expense of causing Cushing's syndrome potassium iodide acts promptly to inhibit thyroid hormone secretion from the Graves' disease thyroid gland. Used more in congenital Graves disease. blockers- alleviate many of the signs and symptoms of Graves Disease However have little effect on the fundamental disease process Palpitations, excessive sweating, and nervousness improve, and tremor and tachycardia are controlled
Potassium Iodide
Adjunctive Therapy:
Radio-Iodine Ablation
Ablation of the thyroid gland with radio-iodine is the
treatment of choice for most adults. After more than 50 years of widespread use, no evidence of an increased risk of malignancy or genetic damage exists. Nonetheless, because of the theoretical risk, frequency of radioiodine therapy is much lower in pediatric patients. 131 I is administered orally in 1-2 doses. Ablation may take several weeks to months, and hyperthyroid symptoms may continue until that time. Propanalol may be used to ameliorate these symptoms.
Surgery
Surgery is the oldest treatment for Graves Disease Generally, patients are initially treated with antithyroid
medications. Iodide then is added before surgery to decrease the vascularity of the thyroid gland. To minimize risk of recurrence, most of the gland is removed. Surgical complications can include hypoparathyroidism and damage to the recurrent laryngeal nerve
Summary
Graves disease is the most common
cause of hyperthyroidism is children but with proper treatment can be successfully managed.
Follow up
Microsomal Antibody
1:400 [<1:100]
Thyroglobulin Antibody
1:160 [<1:10]
The End
References
Dallas J, Foley T. Hyperthyroidism. In: Pediatric Endocrinology. 3rd ed. 1996:401-415 Sugino K, Ito K, Mimura T, et al. Surgical treatment of Graves' disease in children. Thyroid. 2004;14:447-452 Zimmerman D, Lteif AN. Thyrotoxicosis in children. Endocrinol Metab Clin North Am. Mar 1998;27(1):109-26 Bahadada S, Bhansali A, et. Al. Juvemile Hyperthyrodism: an Experience . Indian Pediatrics 2006 43: 301-317 Ferry RJ, et al. Graves disease Published online Rivkees, SA, Sklar C, Freemark M, The Management of Graves Disease in Children with Special Emphasis on Radioiodine Treatment. The Journal of Clincical Endocrinology and Metabolism 1998 83: 3767-3776 Stalberg P, Svensson A, et al. Surgical Treatment of Graves Disease: Evidence-Based Approach World Journal of Surgery 2008 Published online Glaser NS, Styne DM. Predicting the Likilihood of Remission in Children with Graves Disease: A Prospective, Multicenter Study. Pediatrics 2008 121: 481-488 www.endotext.com
Objectives
To present an interesting case of altered
mental status Discuss the differential diagnosis of hyperthyroidism Review the Pathophysiology and treatment of Graves Disease.
Questions
1. Are patients with Graves disease who
do not have their thyroid removed at greater risk for thyroid cancer later on in life? 2. What determines which of the antithyroid medications are used in a patient.
Thanks
Dr. Marshall Dr. Kelly Monica and Archana
Differential
Acute/Chronic
IDDM with DKA Brain tumor with seizure/increased ICP Hypertension with hypertensive encephalopathy
Acute
Ingestion Infection Seizure Aneursym Stroke