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ENDOCRINOLOGY BOARD REVIEW

ENDOCRINOLOGY BOARD REVIEW. THYROID DISORDERS Henri Godbold, MD. General. - Thyroid produces two related hormones thyroxine(T4) and triidothyronine (T3) - Function is through nuclear receptors playing a role in cell differentiation - Maintains thermogensis, and metabolic homeostasis

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ENDOCRINOLOGY BOARD REVIEW

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  1. ENDOCRINOLOGYBOARD REVIEW THYROID DISORDERS Henri Godbold, MD

  2. General - Thyroid produces two related hormones thyroxine(T4) and triidothyronine (T3) - Function is through nuclear receptors playing a role in cell differentiation - Maintains thermogensis, and metabolic homeostasis - Disorders result from autoimmune processes that either stimulate overproduction of hormones (thyrotoxicosis) or glandular destruction and hormone deficiency (hypothyroidism) - Benign nodules and various forms of thyroid cancers

  3. Anatomy - Located anterior to trachea consist two lobes -  Weighs 12-20gm soft and highly vascular a posterior region gland contain four parathyroid gland that produce parathyroid hormone - Lateral borders of the gland is transversed by the recurrent laryngeal nerves - Develops from the floor of the primitive pharynx third week of gestation migrates from the foramen cecum, at the base of tongue along the thyroglossal duct to neck - Hormonal synthesis usually begin at about 11 weeks’ gestation

  4. Thyroid Physiology - Thyroid releases (2) forms of hormones - Thyroxine (T4) and triiodothyroxine (T3) ratio 14:1 - T3 is 80% derived from peripheral tissue - T4 all within the thyroid gland - T3 is produced from T4 in liver, kidneys, pituitary gland and CNS - T3 is the physiologically active in almost all tissue binding to specific nuclear receptors regulating the transcription of thyroid hormone dependent genes

  5. Drugs decreasing Peripheral conversion of T4 to T3 •        Propranolol •        Corticosteroids •        Propylthiouracil (PTU) •        Amiodarone

  6. SYNTHESIS AND RELEASE

  7. - TSH controls release under the influence TRH from the hypothalamus - TSH stimulate thyrocyte function resulting in iodide uptake actively on the basal surface of the thyroid follicle cell - Iodide undergoes oxidation to iodine which iodinates tyrosine residues catalyzed by peroxidase - Thyroglobulin coupling occurs to form mono- and diiodotyrosine (MIT and DIT - Two DITs coupling = T4 - One DIT and one MIT combine =T3 - If iodine scarce, the production of T3 is increase - Activity is dictated by # iodines attached to tyrosine molecules and location

  8. Secretion • Degradation process with endocytosis of the follicular colloid containing MIT, T3, • T4, DIT attached to thyroglobulin undergoes fusion with lyosome resulting in proteolysis release • Deiodination occurs with the recycling iodide and secretion of T3 and T4 • Circulating thyroid hormones are more than 99% protein bound, are thyroxine-binding globulin, albumin, and transthyretin. • 80% of circulating T3 is derived from the conversion of T4 outside the thyroid • Serum half-life of T3 is much shorter than that T4 (1day vs 8days)

  9. Storage - Iodine as iodinated tyrosine of thyroglobins 8000 micrograms total - T4 and T3 represent 600 micrograms each - Enough hormone is stored in the follicular colloid to last 2-3 months 

  10. Overveiw of Thyroid Fx Workup

  11. Measurement RAIU

  12. Drugs and condition that affect thyroid Function Tests

  13. Thyroid Pathology A. Thyroid Gland 1.Multinodular goiter (nontoxic goiter) Presentation i. Females > males ii. Frequently asymptornatic iii. Typically euthyroid iv. Goiter v.Plummer's syndrome:development of hyperthyroidism (toxic multinodular Goiter) late in course

  14. B. GROSS enlarged thyroid gland with multiple colloid nodules C. MICROSCOPIC i.Nodules of varying sizes composed of colloid follicles ii. Calcification, hemorrhage, cystic degeneration, and fibrosis D. LAB: normal T4, T3, and TSH

  15. B Hyperthyroidism 1. General features of hyperthyroidism I a. Clinical features i. Tachycardia and palpitations ii. Nervousness and diaphoresis iii. Heat intolerance iv.Weakness and tremors v. Diarrhea vi. Weight loss despite a good appetite b. Labs i. Elevated free T4ii. Primary hyperthyroidism: decreased TSH

  16. Graves'disease a. Definition: autoimmune diseases characterized by production of IgGautoantibodies to the TSH receptor b. Clinical features i. Females > males; age 20‑40 ii. Hyperthyroidism iii. Diffuse goiter iv. Ophthalmopathy: exophthalmus v. Dermopathy: pretibial myxcdema c. Micro: hyperplastic follicles with scalloped colloid

  17. Other causes of hyperthyroidism a. Toxic multinodular goiter b. Toxic adenoma: functioning adenoma producing thyroid hormone c. Hashimoto’s and subacute thyroiditis (transient hyperthyroidism)

  18. Juvenile Graves Disease • Diffuse hyperplasia • Most common cause of thyrotoxicosis in children and adolescents • Clinical manifestation - muscle weakness - behavior problems - anxiety - cardiomegaly - palpitations - tachycardia - appetite - widen pulse pressure - Tremor - Emotional liability - rapid DTR time - Excessive perspiration • Opthalmopathy, dermopathy, pretibial myxedema rare in children

  19. Test: TSH suppressed and serum T4 high • Treatment: a. Blunting toxic effects circulating T3/T4 b. Stop further increase in production • B-blockers prior to Sx intervention • RAI rarely used in children and adolescences potential risk leukemia, thyroid Ca, and genetic disorder. • Medical management: PTU and methimazole mechanism: Both inhibit the coupling of iodotyrosines, oxidation and binding of iodide

  20. PTU 5-10mg/kg PO div q8hr • Methimazole 0.2 mg/kg PO daily • Once gland cools off and decrease in size tapper drugs • Give synthetic T4 once euthyroid adjust to maintain a euthyroid status

  21. Neonatal Thyrotoxicosis • Due to TSH-receptor stimulating antibodies(TSH) • Transmitted transplacentally in mother with inactive or active Graves or Hashimoto thyroiditis • Presentation: newborn irritability, flushing, tachycardia, HTN, thyromegaly • High total T4, FT4, T3 postnatal blood, low TSH Treatment: a. sedative and digitalis if needed b. Iodide c. Lugol (5% iodine and 10% K iodine) d. Methimazole

  22. Hypothyroidism a. Clinical features i.Fatigue ii. Sensitivity to cold temperatures iii.Decreased cardiac output iv. Myxedema: - Facial and periorbital edema - Peripheral edema of the hands and feet - Deep voice - Macroglossia v.Constipation vi.Anovulatory cycles

  23. b. Lab i. Decrease Free T4 ii. Primary hypothyroidism: elevated TSH Iatrogenic hypothyroidism • Most common cause of hypothyroids in US • Secondary to thyroidectomy or RAI rx • Rx: Levothyroxine 12.5-50mcg PO qd adjusting dose by 12.5-25mcg/d q4-8wks

  24. Congential Hypothyroidism(cretinism) a. Etiology i. Endemic region: iodine deficiency during intrauterine and neonatal life ( worldwide) ii. Non endemic regions: thyroid dysgenesis b. Presentation i. Failure to thrive ii. Stunted bone growth and dwarfism -Commonly absent distal femoral epiphysis iii. Spasticity and motor incoordination iv. Mental retardation v. Goiter (endemic cretinism) ‑Endemic goiter a. Uncommon in the US b. Etiology: dietary deficiency of iodine

  25. Clinical Manifestation congenital Hypothyroidism • Occurs in 1/4000 Worldwide • Most infant are asymptomatic at birth because of transplacental passage of T4 (usu 3rd day of life) • Most common cause is thyroid dysgenesis • Presentation: hypoglycemia, jaundice micropenis, midline facial anomalies, enlarge posterior fontanelle, macroglossia Rx: Initial dose: Sodium L-tyroxine 10-15 microgrms/kg/day( should not be mixed soy protien or iron) Then, 4 micrgms/kg/day

  26. Thyroiditis • Hashimoto's thyroiditis a. Definition: chronic autoimmune disease characterized by immune destruction of the thyroid gland and hypothyroidism b. Most common noniatrogenic cause of hypothyroidism and Goiterin children > 6yo and adults in US c. Clinical presentation i. Females > males; age 40‑65 ii. Painless goiter iii. Hypothyroid iv.Initial inflammation may cause transient hyperthyroidism. d. Gross: pale enlarge gland e. Micro: i. Lymphocytic inflammation with germinal centers ii. Epithelial "Harthle cell" changes f. May be associated with other autoimmune diseases (SLE, RA, SS [Sjogren's syndrome], etc.) g. Complication: increased risk of non‑Hodgkin‘lymphoma (NHL)B‑cell lymphoma

  27. 2. Subacute thyroiditis • a. Synonyms: De Quervain's thyroiditis, granulomatous • thyroiditis • b. Clinical features • i. Second most common form of thyroiditis • ii. Females > males; age 30‑50 • iii. Preceded by a viral illness • iv. Tender, firm, enlarged thyroid gland • v. May have transient hyperthyroidism • c. Micro: granulomatous thyroiditis • d. Prognosis: typically the disease follows a self‑limited course • e. Symptoms: control with analgesics, prednisone very severe dx

  28. Riedel's thyroiditis a. Definition: rare disease of unknown etiology characterized by destruction of the thyroid gland by dense fibrosis and fibrosis of surrounding structures (trachea and esophagus) b. Clinical features i. Females > males; middle age ii. Irregular, hard thyroid that is adherent to adjacentstructures iii. May mimic carcinoma and present with stridor,dyspnea, ordysphagia c.Micro i. Dense fibrous replacement of the thyroid gland ii. Chronic inflammation d. Associated with retroperitoneal and mediastinal fibrosis

  29. Thyroid Neoplasia Adenomas a. Follicular adenomas are the most common b. Clinical features i. Usually painless, solitary nodules In first 20 yrs life likely malignant than older person ii. "Cold nodule" on thyroid scans iii. May be functional and cause hyperthyroidism (toxic adenoma) 2. Papillary carcinoma a. Epidemiology i. Account for 80% of malignant thyroid tumors ii. Females > males; age 20‑50 iii. Risk factor: radiation exposure b. Micro i. The tumor typically exhibits a papillary pattern. ii. Occasional psammoma bodies iii. Characteristic nuclear featuresClear "Orphan Annie eye" nucleiNuclear grooves

  30. Intranuclear cytoplasmic inclusions c. Lymphatic spread to cervical nodes is common. d. Treatment i. Resection is curative in most cases. ii. Radiotherapy with iodine 131 is effective for metastases. e. Prognosis: excellent; 20‑year survival = 90% Follicular carcinoma a. Accounts for 15% of malignant thyroid tumors b. Females > males; age 40‑60 c. Hematogenous metastasis to the bones or lungs is common. d. High mortality rate because most present with distant mets

  31. Medullary carcinoma a. Accounts for 5% of malignant thyroid tumors b. Arises from C cells (parafollicular cells) and secretes calcitonin c. Micro: nests of polygonal cells in an amyloid stroma d. Minority (25%) are associated with MEN 2 and MEN 3 syndromes • Treatment: primarily surgical - Advance disease external RT and chemo

  32. Anaplastic carcinoma a. Presentation i. Females > males; age > 60 ii. Firm, enlarging, bulky mass iii. Dyspnea and dysphagia iv. Tendency for early widespread metastasis and invasion of the trachea and esophagus b. Micro: undifferentiated, anaplastic, and pleornorphic cells c. Prognosis: very aggressive and rapidly fatal

  33. Diagnosis • Fine needle aspirate vs. excision - Hx RT to neck or head - rapidly growing nodule - satellite LN and/or distant mets - Hoarseness or dysphagia Rx: Well differentiated neoplasm should be excised - TSH suppression - RAI ablation

  34. Q1 An 18yo old boy presents with a 1 month history of slowly enlarging neck mass. You palpate a 2-cm mass in the superior lobe of the rt. thyroid with no lymphadenopathy. Of the following, the BEST next step is to: • Begin therapy with RAI • Obtain anteroposterior and lateral CXR • Perform needle bx of the neck • Perform total thyroidectomy • Prescribe oral cephalexin

  35. Q2. 15yo female presents with an asymptomatic goiter. She has type 1 diabetes that was diagnosed at age 7 years Of the following, study that is MOST likely to establish the diagnosis is • Measurement of antiperoxidase antibodies • Needle bx of thyroid • Technetium thyroid scan • Thyroid-binding globulin levels • US of the thyroid

  36. Q3. 44yo male involved in a MVA unresponsive intubated in ICU with multiple orthropedic injuries. He is stabilized medically on day 2 undergoes open reduction and internal fixation of right femur and right humerus. After returning to the ICU, his TSH is 0.3mU/L and total T4 is normal. T3 is 0.6 micrograms/dl. What is the next appropriate step in the management of this patient? • Start levothyroxine • RAIU scan • Thyroid US • Observe patient • Initiate prednisone

  37. Q4. Which of the following statements regarding hypothyroidism is true? • Hashimoto’s thyroiditis is the most common cause of hypothyroidism worldwide • The annual risk of developing overt clinical hypothyroidism from subclinical hypothyroidism in patients with positive thyroid peroxidase antibodies is 20%. • Hashimoto’s is characterized by marked infiltration of thyroid with activated T and B cells • Low TSH excludes the diagnosis of hypothyroidism • Thyroid peroxidase antibodies are present in 50% of patients with autoimmune hypothyroidism

  38. References • American College of Physicians MKSAP 13 • MedStudy Pediatric Board Review • Harrison’s Principle of Internal Medicine

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