Pathology of the thyroid
Derived from pharyngeal epithelium Descends from foramen cecum to lower neck Lingual thyroid or ectopic in neck 2 lobes and isthmus, 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
Normal thyroid gland
Thyroid diseases Hyperthyroidism Hypothyroidism Mass lesions
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
Hyperthyroidism (#thyrotoxicosis)
Clinical features of hyperthyroidism 1. Constitutional 2. Gastrointestinal 3. Cardiac 4. Neuromuscular 5. Ocular 6. Thyroid storm 7. Apathetic
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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
Thyroid scan
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
Hypothyroidism Clinical Features: Cretinism Myxedema Diagnosis: high TSH Low T4
Thyroiditis
Hashimoto’s thyroiditis F>>M, 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
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Hashimoto’s thyroiditis F>>M, 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
Hashimoto’s thyroiditis
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Fibrosing variant
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
Gran u lomato u s thyro i d itis
Palpation thyroiditis Riedel thyroiditis
Graves’ disease F>>M, 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
Triad of Graves Hyperthyriodism Ophthalmopathy Dermopathy
Graves’ disease
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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
Goiter
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Goiter
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
Thyroid FNA is a diagnostic test
Thyroid FNA
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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Downloaded from: StudentConsult (on 4 October :26 AM) © 2005 Elsevier Follicular adenoma
Follicular Adenoma
Hurthle cell adenoma
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%
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
Papillary carcinoma
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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
Follicular carcinoma
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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
Medullary carcinoma
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Downloaded from: StudentConsult (on 4 October :26 AM) © 2005 Elsevier Medullary carcinoma
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
Anaplastic carcinoma