 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





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

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

 Clinical Features:
Cretinism
Myxedema
 Diagnosis: high TSH
Low T4

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

Pathogenesis of Hashimoto’s thyroiditis

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

Hashimoto’s thyroiditis
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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 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, 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

Triad of Graves
Hyperthyriodism
Ophthalmopathy
Dermopathy

Graves’ disease

Graves’ disease

Graves’ disease

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

Goiter

Multinodular goiter
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Goiter

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

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

Follicular adenoma
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Follicular adenoma

Follicular adenoma

Follicular adenoma

Follicular adenoma
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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

Papillary carcinoma

Papillary carcinoma

Papillary carcinoma
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 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

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

Medullary carcinoma
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Medullary carcinoma
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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

Anaplastic carcinoma