Download MBBS Pathology PPT 8 Thyroid Disorder Lecture Notes

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? Thyroiditis
? Diffuse and Multinodular Goiters
? Neoplasms of the Thyroid
? Congenital cyst
? TFT

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? Hyperthyroidism-Thyrotoxicosis is a hypermetabolic state caused by

elevated circulating levels of free T3 and T4

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? Primary
? Secondary
? most common causes of thyrotoxicosis
?Diffuse hyperplasia of the thyroid associated with Graves disease

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(approximately 85% of cases)

? Hyperfunctional multinodular goiter
? Hyperfunctional thyroid adenoma

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Clinical manifestation-
? weight loss despite increased appetite
? left ventricular dysfunction

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? hypermotility, diarrhea, and malabsorption
? Proximal muscle weakness and decreased muscle mass are common

(thyroid myopathy)

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? osteoporosis
Thyroid storm-
? underlying Graves disease
? during infection, surgery, cessation of antithyroid medication, or any

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form of stress.

? febrile and present with tachycardia
apathetic hyperthyroidism-

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vHypothyroidism-structural or functional derangement that interferes

with the production of thyroid hormone

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? Primary
? Secondary

Primary hypothyroidism-
?Congenital- endemic iodine deficiency

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?Autoimmune-
? most common cause of hypothyroidism in iodine-sufficient areas of

the world

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? Hashimoto thyroiditis
? Circulating autoantibodies, including antimicrosomal, antithyroid

peroxidase, and antithyroglobulin antibodies

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?Iatrogenic-
? Surgical resection
? Radiation
? drugs
Clinical manifestations of hypothyroidism

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? Cretinism
? Myxedema

1.Cretinism- congenital hypothyroidism
ETIOPATHOGENESIS-

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1.Developmental anomalies
2. Genetic defect in thyroid hormone synthesis
3. Foetal exposure to iodides and antithyroid drugs
4. Endemic cretinism
? CLINICAL FEATURES-slow to thrive, poor feeding, constipation, dry

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scaly skin, hoarse cry and bradycardia

? rise in TSH level and fall in T3 and T4 levels

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? Myxoedema-non-pitting oedema due to accumulation of hydrophilic

mucopolysaccharides in the ground substance of dermis and other

tissues

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ETIOPATHOGENESIS.
1.Ablation of the thyroid by surgery or radiation
2. Autoimmune (lymphocytic) thyroiditis (termed primary idiopathic

myxoedema)

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3. Endemic or sporadic goitre
4. Hypothalamic-pituitary lesions

? CLINICAL FEATURES-cold intolerance, mental and physical lethargy,

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constipation
? Thyroiditis
1. Hashimoto thyroiditis
2. granulomatous (de Quervain) thyroiditis
3. subacute lymphocytic thyroiditis

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? Hashimoto Thyroiditis-destruction of the thyroid gland and gradual

and progressive thyroid failure.

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Pathogenesis-
? Anti -thyroglobulin and anti-thyroid peroxidase Ab
? Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and protein

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tyrosine phosphatase-22 (PTPN22)


MORPHOLOGY-
? gross-diffusely enlarged

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? Cut surface- firm, pale, yellow-tan
Clinical Course.
? Hypothyroidism
? preceded by transient thyrotoxicosis
? Increased risk for developing other autoimmune diseases

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? Subacute Lymphocytic (Painless) Thyroiditis- subset of HT
similar to Hashimoto thyroiditis, however, fibrosis and H?rthle cell

metaplasia are not prominent.

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Granulomatous Thyroiditis-
De Quervain thyroiditis
? 40 and 50
? F:M(4:1)

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Pathogenesis-
? viral infection
MORPHOLOGIC FEATURES.
? Grossly, asymmetric moderate enlargement
? Cut surface-firm and yellowish-white

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Microscopically-vary to the stage
? acute inflammation
? granulomatous appearance
? advanced cases may show fibroblastic proliferation

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? RIEDEL'S THYROIDITIS-
MORPHOLOGIC FEATURES.
? Grossly-contracted, stony-hard, asymmetric

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? Cut section- hard and devoid of lobulations
? Microscopically, there is extensive fibrocollagenous replacement,

marked atrophy of the thyroid parenchyma
GRAVES' DISEASE (DIFFUSE TOXIC GOITRE)-

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? most common cause of endogenous hyperthyroidism
Clinical findings
? Hyperthyroidism (thyrotoxicosis)
? Diffuse thyroid enlargement
? Ophthalmopathy

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ETIOPATHOGENESIS-
? Genetic factor association-HLA-DR3, CTLA-4 and PTPN22
? Autoimmune disease association
? Autoantibodies- against TSH-receptor autoantigen

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?Thyroid-stimulating immunoglobulin (TSI)
?Thyroid growth-stimulating immunoglobulins
?TSH-binding inhibitor immunoglobulins
? Other factors-female,stress, and smoking

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MORPHOLOGIC FEATURES-
? Grossly-moderately, diffusely and symmetrically enlarged
? Cut surface-homogeneous, red-brown and meaty and lacks the

normal translucency

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Histology-
? epithelial hyperplasia
? colloid is markedly diminished

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? increased vascularity and accumulation of lymphoid cells


GOITRE-Thyroid enlargement caused by compensatory hyperplasia and

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hypertrophy of the follicular epithelium in response to thyroid

hormone deficiency
?Diffuse goitre (simple nontoxic goitre or colloid goitre).
?Nodular goitre (multinodular goitre or adenomatous goitre).

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? ETIOLOGY. Epidemiologically, goitre occurs in 2 forms: endemic, and

non-endemic or sporadic.

qEndemic goitre.

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? Endemic zone- more than 10% of the population is termed endemic

goitre

? Goitrogens

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qSporadic (non-endemic) goitre-
? Increased demand as in puberty and pregnancy
? Genetic factors.
? germline mutations in DICER1 gene

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?PTEN hamartoma tumor syndrome
? Dietary goitrogenes
? Drug induced goiter
? Hereditary defect in thyroid hormone synthesis and transport
? Inborn errors of iodine metabolism

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MORPHOLOGIC FEATURES-
? Gross-moderate enlargement,symmetric and diffuse
? Cut surface-gelatinous and translucent brown
Histologically -stage

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? Hyperplastic stage-papillae,new follicles
? Involution stage-large follicles distended by colloid and lined by

flattened follicular epithelium
Nodular Goitre (Multinodular Goitre, Adenomatous Goitre)-

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? nodular goitre is regarded as the end-stage of long-standing simple

goitre.

? tumour-like enlargement of the thyroid gland and characteristic

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nodularity

MORPHOLOGIC FEATURES.

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? Grossly, asymmetric and extreme enlargement, weighing 100-500 gm

or even more

? Five cardinal macroscopic features are as under

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1. Nodularity with poor encapsulation

2. Fibrous scarring

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3. Haemorrhages

4. Focal calcification

5. Cystic degeneration

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? Cut surface- poorly-circumscribed multinodular
Histologically,
? Partial or incomplete encapsulation of nodules

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? follicles varying from small to large
? Areas of haemorrhages
? Fibrous scarring with foci of calcification
? Micro-macrocystic change

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THYROID TUMOURS

FOLLICULAR ADENOMA-most common
Pathogenesis-Somatic mutations of the TSH receptor signal ing

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pathway are found in toxic adenomas, as well as in toxic multinodular

goiter.
? TSHR and GNAS mutations,50%

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? RAS or PIK3CA (<20%)
? <10% of follicular adenomas harbor PAX8- PPARG fusion genes
MORPHOLOGIC FEATURES.
? Grossly, the follicular adenoma is characterised by four features
1.solitary nodule

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2. complete encapsulation
3. clearly distinct architecture inside and outside the capsule
4. compression of the thyroid parenchyma outside the capsule

? small ,up to 3 cm in diameter

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? cut section-grey-white to red-brown
Histologically,
? complete fibrous encapsulation
? epithelial cells forming follicles of various size
? surrounding thyroid tissue shows signs of compression

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Thyroid Carcinoma

Major subtypes of thyroid carcinoma-
? Papillary carcinoma (>85% of cases)
? Follicular carcinoma (5% to 15% of cases)

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? Anaplastic (undifferentiated) carcinoma (<5% of cases)
? Medullary carcinoma (5% of cases)


Papillary Carcinomas-

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? Fusion gene RET/PTC
(RET/papillary thyroid carcinoma) and are present in approximately

20% to 40%
? NTRK1, 5-10%

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? BRAF gene, advance stage
Follicular Carcinomas-
? RAS or the PI-3K/AKT
? PIK3CA amplifications
? PTEN, a tumor suppressor gene

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Anaplastic (Undifferentiated) Carcinomas-RAS or PIK3CA mutations)
Second hit ,inactivation of TP53 or activating mutations of -catenin

Medullary Thyroid Carcinomas-

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? MEN-2 syndrome
? RET mutations
Papil ary Carcinoma-
most common form of thyroid cancer
MORPHOLOGY-

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Gross-
solitary or multifocal
Cut surface-greyish-white, hard, Fibrosis,calcification and papillary foci

microscopic hallmarks-

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? branching papillae
? Ground glass or Orphan Annie eye nuclei,intranuclear cytoplasmic

inclusion

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? Psammoma bodies

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Variants-
? follicular variant
? tall-cell variant
? diffuse sclerosing variant

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? papillary microcarcinoma

Fol icular Thyroid Carcinoma-
? 5% to 15% of primary thyroid cancers, but are more frequent in areas

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with dietary iodine deficiency

MORPHOLOGY-
? Solitary nodule
? Cut surface-grey-white with areas of haemorrhages, necrosis and cyst

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formation


Microscopically,-

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? follicles of various sizes,solid trabecular pattern
? Vascular invasion and direct extension
? lymphatic invasion is rare

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Anaplastic (Undifferentiated) Carcinoma-
? <5%
? 100% moratality
Microscopy-
? pleomorphic giant cells

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? spindle cells
? mixed spindle and giant cells


Medul ary Carcinoma

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Congenital Anomalies-
Thyroglossal duct cyst
? most common congenital neck mass
? Midline neck

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