Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Pathology PPT 8 Thyroid Disorder Lecture Notes
THYROID DISORDER
? Hyperthyroidism
? Hypothyroidism
? Thyroiditis
? Diffuse and Multinodular Goiters
? Neoplasms of the Thyroid
? Congenital cyst
? TFT
? Hyperthyroidism-Thyrotoxicosis is a hypermetabolic state caused by
elevated circulating levels of free T3 and T4
? Primary
? Secondary
? most common causes of thyrotoxicosis
?Diffuse hyperplasia of the thyroid associated with Graves disease
(approximately 85% of cases)
? Hyperfunctional multinodular goiter
? Hyperfunctional thyroid adenoma
Clinical manifestation-
? weight loss despite increased appetite
? left ventricular dysfunction
? hypermotility, diarrhea, and malabsorption
? Proximal muscle weakness and decreased muscle mass are common
(thyroid myopathy)
? osteoporosis
Thyroid storm-
? underlying Graves disease
? during infection, surgery, cessation of antithyroid medication, or any
form of stress.
? febrile and present with tachycardia
apathetic hyperthyroidism-
vHypothyroidism-structural or functional derangement that interferes
with the production of thyroid hormone
? Primary
? Secondary
Primary hypothyroidism-
?Congenital- endemic iodine deficiency
?Autoimmune-
? most common cause of hypothyroidism in iodine-sufficient areas of
the world
? Hashimoto thyroiditis
? Circulating autoantibodies, including antimicrosomal, antithyroid
peroxidase, and antithyroglobulin antibodies
?Iatrogenic-
? Surgical resection
? Radiation
? drugs
Clinical manifestations of hypothyroidism
? Cretinism
? Myxedema
1.Cretinism- congenital hypothyroidism
ETIOPATHOGENESIS-
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
scaly skin, hoarse cry and bradycardia
? rise in TSH level and fall in T3 and T4 levels
? Myxoedema-non-pitting oedema due to accumulation of hydrophilic
mucopolysaccharides in the ground substance of dermis and other
tissues
ETIOPATHOGENESIS.
1.Ablation of the thyroid by surgery or radiation
2. Autoimmune (lymphocytic) thyroiditis (termed primary idiopathic
myxoedema)
3. Endemic or sporadic goitre
4. Hypothalamic-pituitary lesions
? CLINICAL FEATURES-cold intolerance, mental and physical lethargy,
constipation
? Thyroiditis
1. Hashimoto thyroiditis
2. granulomatous (de Quervain) thyroiditis
3. subacute lymphocytic thyroiditis
? Hashimoto Thyroiditis-destruction of the thyroid gland and gradual
and progressive thyroid failure.
Pathogenesis-
? Anti -thyroglobulin and anti-thyroid peroxidase Ab
? Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and protein
tyrosine phosphatase-22 (PTPN22)
MORPHOLOGY-
? gross-diffusely enlarged
? Cut surface- firm, pale, yellow-tan
Clinical Course.
? Hypothyroidism
? preceded by transient thyrotoxicosis
? Increased risk for developing other autoimmune diseases
? Subacute Lymphocytic (Painless) Thyroiditis- subset of HT
similar to Hashimoto thyroiditis, however, fibrosis and H?rthle cell
metaplasia are not prominent.
Granulomatous Thyroiditis-
De Quervain thyroiditis
? 40 and 50
? F:M(4:1)
Pathogenesis-
? viral infection
MORPHOLOGIC FEATURES.
? Grossly, asymmetric moderate enlargement
? Cut surface-firm and yellowish-white
Microscopically-vary to the stage
? acute inflammation
? granulomatous appearance
? advanced cases may show fibroblastic proliferation
? RIEDEL'S THYROIDITIS-
MORPHOLOGIC FEATURES.
? Grossly-contracted, stony-hard, asymmetric
? Cut section- hard and devoid of lobulations
? Microscopically, there is extensive fibrocollagenous replacement,
marked atrophy of the thyroid parenchyma
GRAVES' DISEASE (DIFFUSE TOXIC GOITRE)-
? most common cause of endogenous hyperthyroidism
Clinical findings
? Hyperthyroidism (thyrotoxicosis)
? Diffuse thyroid enlargement
? Ophthalmopathy
ETIOPATHOGENESIS-
? Genetic factor association-HLA-DR3, CTLA-4 and PTPN22
? Autoimmune disease association
? Autoantibodies- against TSH-receptor autoantigen
?Thyroid-stimulating immunoglobulin (TSI)
?Thyroid growth-stimulating immunoglobulins
?TSH-binding inhibitor immunoglobulins
? Other factors-female,stress, and smoking
MORPHOLOGIC FEATURES-
? Grossly-moderately, diffusely and symmetrically enlarged
? Cut surface-homogeneous, red-brown and meaty and lacks the
normal translucency
Histology-
? epithelial hyperplasia
? colloid is markedly diminished
? increased vascularity and accumulation of lymphoid cells
GOITRE-Thyroid enlargement caused by compensatory hyperplasia and
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).
? ETIOLOGY. Epidemiologically, goitre occurs in 2 forms: endemic, and
non-endemic or sporadic.
qEndemic goitre.
? Endemic zone- more than 10% of the population is termed endemic
goitre
? Goitrogens
qSporadic (non-endemic) goitre-
? Increased demand as in puberty and pregnancy
? Genetic factors.
? germline mutations in DICER1 gene
?PTEN hamartoma tumor syndrome
? Dietary goitrogenes
? Drug induced goiter
? Hereditary defect in thyroid hormone synthesis and transport
? Inborn errors of iodine metabolism
MORPHOLOGIC FEATURES-
? Gross-moderate enlargement,symmetric and diffuse
? Cut surface-gelatinous and translucent brown
Histologically -stage
? Hyperplastic stage-papillae,new follicles
? Involution stage-large follicles distended by colloid and lined by
flattened follicular epithelium
Nodular Goitre (Multinodular Goitre, Adenomatous Goitre)-
? nodular goitre is regarded as the end-stage of long-standing simple
goitre.
? tumour-like enlargement of the thyroid gland and characteristic
nodularity
MORPHOLOGIC FEATURES.
? Grossly, asymmetric and extreme enlargement, weighing 100-500 gm
or even more
? Five cardinal macroscopic features are as under
1. Nodularity with poor encapsulation
2. Fibrous scarring
3. Haemorrhages
4. Focal calcification
5. Cystic degeneration
? Cut surface- poorly-circumscribed multinodular
Histologically,
? Partial or incomplete encapsulation of nodules
? follicles varying from small to large
? Areas of haemorrhages
? Fibrous scarring with foci of calcification
? Micro-macrocystic change
THYROID TUMOURS
FOLLICULAR ADENOMA-most common
Pathogenesis-Somatic mutations of the TSH receptor signal ing
pathway are found in toxic adenomas, as well as in toxic multinodular
goiter.
? TSHR and GNAS mutations,50%
? 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
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
? 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
Thyroid Carcinoma
Major subtypes of thyroid carcinoma-
? Papillary carcinoma (>85% of cases)
? Follicular carcinoma (5% to 15% of cases)
? Anaplastic (undifferentiated) carcinoma (<5% of cases)
? Medullary carcinoma (5% of cases)
Papillary Carcinomas-
? Fusion gene RET/PTC
(RET/papillary thyroid carcinoma) and are present in approximately
20% to 40%
? NTRK1, 5-10%
? BRAF gene, advance stage
Follicular Carcinomas-
? RAS or the PI-3K/AKT
? PIK3CA amplifications
? PTEN, a tumor suppressor gene
Anaplastic (Undifferentiated) Carcinomas-RAS or PIK3CA mutations)
Second hit ,inactivation of TP53 or activating mutations of -catenin
Medullary Thyroid Carcinomas-
? MEN-2 syndrome
? RET mutations
Papil ary Carcinoma-
most common form of thyroid cancer
MORPHOLOGY-
Gross-
solitary or multifocal
Cut surface-greyish-white, hard, Fibrosis,calcification and papillary foci
microscopic hallmarks-
? branching papillae
? Ground glass or Orphan Annie eye nuclei,intranuclear cytoplasmic
inclusion
? Psammoma bodies
Variants-
? follicular variant
? tall-cell variant
? diffuse sclerosing variant
? papillary microcarcinoma
Fol icular Thyroid Carcinoma-
? 5% to 15% of primary thyroid cancers, but are more frequent in areas
with dietary iodine deficiency
MORPHOLOGY-
? Solitary nodule
? Cut surface-grey-white with areas of haemorrhages, necrosis and cyst
formation
Microscopically,-
? follicles of various sizes,solid trabecular pattern
? Vascular invasion and direct extension
? lymphatic invasion is rare
Anaplastic (Undifferentiated) Carcinoma-
? <5%
? 100% moratality
Microscopy-
? pleomorphic giant cells
? spindle cells
? mixed spindle and giant cells
Medul ary Carcinoma
Congenital Anomalies-
Thyroglossal duct cyst
? most common congenital neck mass
? Midline neck
This post was last modified on 07 April 2022