pathology of the thyroid. derived from pharyngeal epithelium descends from foramen cecum to lower...
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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