1. Pathology of the thyroid

2. Derived from pharyngeal epithelium Descends from foramen cecum to lower neck Lingual thyroid or ectopic in neck 2 lobes and isthmus, 15-25 gr, richly vascular Follicular cells : T4 Parafollicular cells : Calcitonin T4,3 mostly bind to TBG, the remaining FT4,3 T3 10 folds greater affininty than T4 TRH TSH T4 T3

4. Normal thyroid gland

6. Thyroid diseases Hyperthyroidism Hypothyroidism Mass lesions

7. Causes of thyrotoxicosis With hyperthyroidism Primary 1. Graves disease 2. Toxic multinodular goiter 3. Toxic adenoma Secondary TSH-secreting pituitary adenoma (rare) Without Hyperthyroidism Thyroiditis (Subacute granulomatous/lymphocytic) Struma ovarii Factitious thyrotoxicosis

8. Hyperthyroidism (#thyrotoxicosis)

9. Clinical features of hyperthyroidism 1. Constitutional 2. Gastrointestinal 3. Cardiac 4. Neuromuscular 5. Ocular 6. Thyroid storm 7. Apathetic

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11. Diagnosis of hyperthyroidism 1. Low TSH 2. High T4 3. Radioiodine uptake In secondary hyperthyroidism, TSH is normal or raised T3 toxicosis: Normal T4, High T3

12. Thyroid scan

13. Causes of hypothyroidism Primary 1. Postablative: surgery, radioiodine, radiation 2. Hashimoto thyroiditis* 3. I- deficiency* 4. Congenital defect (dyshormonogenetic goiter)* 5. Drugs (Li, I, p-aminosalicylic acid)* 6. Rare developmental abnormalities of thyroid (thyroid dysgenesis) Secondary Pituitary or hypothalamic failure (uncommon) * Goiterous hypothyroidism

14. Hypothyroidism Clinical Features: Cretinism Myxedema Diagnosis: high TSH Low T4

15. Thyroiditis

16. Hashimoto’s thyroiditis F>>M, 45-65 yr Most common thyroiditis in I sufficeint areas Autoimmune: CD 4 T cells (cytokine mediated), CD 8 cytotoxicity, Ab-dep cell mediated cytotoxicity by NK cells

17. Downloaded from: StudentConsult (on 4 October 2010 11:26 AM) © 2005 Elsevier Pathogenesis of Hashimoto’s thyroiditis

18. Hashimoto’s thyroiditis F>>M, 45-65 yr Most common thyroiditis in I sufficeint areas Autoimmune: CD 4 T cells (cytokine mediated), CD 8 cytotoxicity, Ab-dep cell mediated cytotoxicity by NK cells AutoAbs: anti TG, anti PO, anti TSHR Genetic: HLA DR3, HLA DR5, CTLA-4 Hypothyroidism, Hashitoxicosis Increased risk of B-cell non Hodgkin lymphoma

19. Hashimoto’s thyroiditis

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22. Fibrosing variant

23. Other thyroiditis Infectious: Rare, painful Subacute granulomatous (De Quervain’s) Painful, post-viral, enlargement of 1 or 2 lobes, granulomatous inflammation, sudden or gradual hyperthyroidism, self limited Subacute lymphocytic (Silent) Painless, postpartum, Autoimmune, initial phase Of hyperthyroidism followed by euthyroidism Reidel: Autoimmune, diffuse fibrosis Palpation

24. Gran u lomato u s thyro i d itis

25. Palpation thyroiditis Riedel thyroiditis

26. Graves’ disease F>>M, 20-40 yr Most common cause of endogenous hyperthyroidism Genetic: HLA-B8 and DR3, CTLA4, PTPN22 Anti TSHR, Anti TG, anti thyroid peroxisdase Anti TSHR: Thyroid stimulating Ig, TGI (growth), TBII (Inhibitory) Autoimmune thyroid disease span a spectrum from Graves to Hashimoto’s

27. Triad of Graves Hyperthyriodism Ophthalmopathy Dermopathy

28. Graves’ disease

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32. Goiter Most common thyroid disease Diffuse / nodular Endemic goiter (Geograhpic distribution) > 10% Sporadic goiter (Increased demand, substances interfere with synthesis) Dyshormonogenetic goiter Euthyroidism, Plummer syn, hypothyroidism Nodularity: Recurrent episodes of hyperplasia/involution Variation among cells in response to external stimuli

33. Goiter

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37. Goiter

40. Thyroid neoplasms Often present as solitary thyroid nodule Very common Mostly benign Increased chance of malignancy if: Solitary Young Male Hx of radiation Cold nodule

41. Thyroid FNA is a diagnostic test

42. Thyroid FNA

43. Follicular adenoma Solitary in a lobe Soft to firm Cold to hot Activating mutations in TSH receptor causes high cAMP 20% mutations in RAS oncogene (Also in follicular carcinoma) Often non functional, toxic

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49. Follicular Adenoma

50. Hurthle cell adenoma

51. Thyroid carcinomas ~ 1% of CA related death F >M Mostly in adults, children (papillary CA) Mostly well diff Risk factors: Radiation in childhood, I-def  Papillary CA: 75-85%  Follicular CA: 10-20%  Meduallary CA: 5%  Anaplastic CA< 5%

52. Papillary carcinoma Most common thyroid CA Young age Genetic: MAP kinase signaling pathway  ret/PTC or NTRK1 rearrangements  BRAF oncogene point mutation Hx of radiation in childhood (RET rearrangement) Painless mass/ cervical lymphadenopathy Indolent course

53. Papillary carcinoma

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60. Follicular Carcinoma Second most common CA Older age (middle age) I -deficiency (nodular goiter) RAS mutation, PAX-PPAR ϒ 1 Cold nodule Blood metastasis common LN metastasis uncommon

61. Follicular carcinoma

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64. Medullary carcinoma Derived from C cells 80% sporadic 20%: MEN II, familial medullary CA RET point mutations > 40 yr, MEN II younger age Mass in thyroid, secretion of hormones Raised serum calcitonin, somatostatin, serotonin, VIP Prophylactic thyroidectomy

65. Medullary carcinoma

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68. Anaplastic carcinoma Elderly, mean=65 yr Rare Lethal  Hx of goiter  Hx of differentiated thyroid CA  Concurrent thyroid CA (papillary) Loss of funcrion of p53

69. Anaplastic carcinoma