Pathology of the thyroid. Derived from pharyngeal epithelium Descends from foramen cecum to lower...

Pathology of the thyroid

Derived from pharyngeal epitheliumDescends from foramen cecum to lower neckLingual thyroid or ectopic in neck2 lobes and isthmus, 15-25 gr, richly vascularFollicular cells : T4Parafollicular 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

HyperthyroidismHypothyroidismMass lesions

Causes of thyrotoxicosisWith hyperthyroidismPrimary1.Graves disease 2.Toxic multinodular goiter3.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.Constitutional2.Gastrointestinal3.Cardiac4.Neuromuscular5.Ocular6.Thyroid storm7.Apathetic

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Hyperthyroidism

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 hypothyroidismPrimary 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

HypothyroidismClinical Features: Cretinism Myxedema

Diagnosis: high TSH Low T4

Thyroiditis

Hashimoto’s thyroiditisF>>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

Pathogenesis of Hashimoto’s thyroiditis

Hashimoto’s thyroiditisF>>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 TSHRGenetic: HLA DR3, HLA DR5, CTLA-4Hypothyroidism, HashitoxicosisIncreased risk of B-cell non Hodgkin

lymphoma

Hashimoto’s thyroiditis

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Hashimoto’s thyroiditis

Hashimoto’s thyroiditis

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 limitedSubacute lymphocytic (Silent)

Painless, postpartum, Autoimmune, initial phase

Of hyperthyroidism followed by euthyroidismReidel: Autoimmune, diffuse fibrosisPalpation

Granulomatous thyroiditis

Palpation thyroiditis Riedel thyroiditis

Graves’ diseaseF>>M, 20-40 yrMost common cause of endogenous

hyperthyroidismGenetic: HLA-B8 and DR3, CTLA4, PTPN22Anti TSHR, Anti TG, anti thyroid peroxisdaseAnti TSHR: Thyroid stimulating Ig, TGI

(growth), TBII (Inhibitory)Autoimmune thyroid disease span a spectrum

from Graves to Hashimoto’s

Triad of Graves Hyperthyriodism OphthalmopathyDermopathy

Graves’ disease

Graves’ disease

Graves’ disease

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Graves’ disease

Goiter Most common thyroid diseaseDiffuse / nodularEndemic goiter (Geograhpic distribution) > 10%Sporadic goiter (Increased demand, substances interfere

with synthesis)Dyshormonogenetic goiter Euthyroidism, Plummer syn, hypothyroidismNodularity:

Recurrent episodes of hyperplasia/involution

Variation among cells in response to external stimuli

Goiter

Goiter

Goiter

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Multinodular goiter

Goiter

Goiter

Goiter

Thyroid neoplasmsOften present as solitary thyroid

noduleVery commonMostly benign Increased chance of malignancy if: SolitaryYoungMaleHx of radiationCold nodule

Thyroid FNA is a diagnostic test

Thyroid FNA

Follicular adenomaSolitary in a lobeSoft to firmCold to hotActivating mutations in TSH

receptor causes high cAMP20% mutations in RAS oncogene

(Also in follicular carcinoma)Often non functional, toxic

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Follicular adenoma

Follicular adenoma

Follicular adenoma

Follicular adenoma

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Follicular adenoma

FollicularAdenoma

Hurthle cell adenoma

Thyroid carcinomas~ 1% of CA related deathF >MMostly in adults, children (papillary CA)Mostly well diffRisk factors: Radiation in childhood, I-def Papillary CA: 75-85%Follicular CA: 10-20%Meduallary CA: 5%Anaplastic CA< 5%

Papillary carcinomaMost common thyroid CAYoung ageGenetic: MAP kinase signaling pathwayret/PTC or NTRK1 rearrangementsBRAF oncogene point mutationHx of radiation in childhood (RET

rearrangement)Painless mass/ cervical lymphadenopathyIndolent course

Papillary carcinoma

Papillary carcinoma

Papillary carcinoma

Papillary carcinoma

Papillary carcinoma

Papillary carcinoma

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Papillary carcinoma

Follicular CarcinomaSecond most common CAOlder age (middle age)I-deficiency (nodular goiter)RAS mutation, PAX-PPAR ϒ1Cold noduleBlood metastasis commonLN metastasis uncommon

Follicular carcinoma

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Follicular carcinoma

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Follicular carcinoma

Medullary carcinomaDerived from C cells80% sporadic20%: MEN II, familial medullary CARET point mutations> 40 yr, MEN II younger ageMass in thyroid , secretion of hormonesRaised serum calcitonin, somatostatin,

serotonin, VIPProphylactic thyroidectomy

Medullary carcinoma

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Medullary carcinoma

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Medullary carcinoma

Anaplastic carcinoma• Elderly, mean=65 yr• Rare• Lethal Hx of goiter Hx of differentiated thyroid CAConcurrent thyroid CA (papillary)• Loss of funcrion of p53

Anaplastic carcinoma

Anaplastic carcinoma

Anaplastic carcinoma