• THYROID GLAND
• Ectopic thyroid =MC at base of tongue (lingual thyroid)
• Histology = lobules composed of about 20 to 40 evenly dispersed follicles lined
by Cuboidal to low columnar epithelium
• Physiology = In periphery, free T4 T3
• T3 receptors = on nuclear membranes of in target cells
• up-regulation of carbohydrate and lipid catabolism
• stimulation of protein synthesis
• ↑ BMR
• act on all cells in the body
• Thyroid, steroid & vitamin D receptors are in the nucleus
• parafollicular cells, or C cells =secrete the hormone calcitonin
• Both hypo and hyperthyroidism produce – HTN
• Pharmacology = Goitrogens ( mustard seeds and cabbage contain)
• suppress T3 and T4 synthesis, TSH increases-(Goiter)
• Propylthiouracil inhibits the oxidation of iodide ( inhibits thyroid
peroxidase) ( indicated in pregnancy)
• Iodide blocks the release of thyroid hormones
• Best screening test for both hypo and hyper thyroid is = TSH
THYROID GLAND
THYROID GLAND
• Pathology
• Hyperthyroidism
• Grave’s Disease
• Hypothyroidism
• Cretinism
• Myxedema
• Thyroiditis
• Hashimoto’s
• Subacute
• Granulomatous
• Lymphocytic (painless)
• Diffuse & Multinodular Goiter
• Neoplasms
• Hyperthyroidism
• Causes: MCC - Graves’ disease (85% of cases)
• Others = Toxic multinodular goiter ,Toxic adenoma, Struma ovarii
• Characterized by = Hyper metabolic state
• clinical: Nervousness, warm moist skin, fine tremors ( intention and resting),
palpitations, rapid pulse ( sleeping pulse > 100/min), exophthalmos, weight loss,
heat intolerance, muscle atrophy & weakness, osteoporosis
• lab: ↑ circulating T3 & ↑ T4, ↓TSH
• Graves’ disease
• Peak age -20-40 yrs.
• ↑incidence in females (F/M 10:1)
• Pathogenesis: Autoimmune disorder of thyroid gland
• IgG antibodies against TSH receptors ( LATS)
• IgG act as agonists on receptors Increasing thyroid hormone secretion.
• Genetics : Familial ( HLA-B8 & HLA-DR3 association)
• Clinically: Symmetrical thyroid enlargement , Hyperthyroidism,
Opthalmopathy, Proptosis or exophthalmia , Dermopathy (pretibial
myxedema)
• Lab : T3 & T4, TSH , radioactive iodine uptake I-131
GRAVES’ DISEASE (HYPERTHRYRIODISM)
Scalloped appearance = hyperfunctioning gland
• Hypothyroidism
• Causes= MCC in adults is Hashimoto’s Thyroiditis
• Others = dietary iodine deficiency, Thyroid dysgenesis
• Characterized by = Hypometabolic state
• Clinical:
• Cretinism = In children
• severe mental retardation, short stature, coarse facial features
(protruding tongue due to↑ deposition of GAG’s= glycosaminoglycans )
• Myxedema = in adults (GAG’s deposition results in non-pitting edema,
Coarsening of facial features,
• Clinical features :
• Slowing of physical and mental activity= Fatigue, lethargy, slowed
speech, mental sluggishness, cold intolerance, weight gain , hyper
cholesterolism
• ↓ in sympathetic activity =Constipation, sweating, bradycardia
• Hypothyroidism
• Hashimoto’s Thyroiditis
• Age- 45-65 yrs.
• F:M – 10 to 20:1
• MCC of hypothyroidism in USA
• Familial = HLA-DR3 or HLA-DR5 Associated (weak)
• Clinically= Seen predominately in middle-aged women as diffuse painless
enlargement of the gland
• Pathogenesis = Autoimmune disorder
• anti-thyroid antibodies AGAINST:
1. Thyroid peroxidase
2. TSH-receptors blocking of thyroid hormone receptors
3. Iodine transporter –
4. Thyroglobulin (TGB)
• Thyroid injury= mediated by complement fixing Cytotoxic antibodies,
ADCC & CD8+ Cytotoxic cells
• Associated conditions = Turner’s and Down’s
• Lab= ↓T3,↓T4, ↑TSH & antibodies
• Risk of = SLE, Sjogren's, DM (Type- I), NHL ( B cell)
HASHIMOTO’S THYROIDITIS
Pathogenesis
HASHIMOTO’S THYROIDITIS
Pathology
Histology:
lymphoid aggregate tissue with
reactive germinal centers
Hurthle cell change eosinophilic
cytoplasm)
Destruction of follicles
Fibrosis
Goiter
Diffuse Nodular
Nontoxic (simple)
Toxic
& Multinodular
MC- Grave’s STN
MC- Hashimoto’s (euthyroid)
(Hyper) (Hypo)
Benign (MC)
Malignant
• Thyroiditis
• 1. Hashimoto’s
• 2. Sub acute Granulomatous or De Quervain’s
• Age = 30-50 yrs.
• F:M- 3-5:1
• Etiopathgenesis = Viral or post viral ( Coxsackie's, Mumps, Measles,
Adeno)
• Pathology = Early- Micro abscess, Neutrophils
• Late – Granulomas with multinucleate giant cells
• Clinical course = past history of URI
• Painful neck swelling
• Initial transient hyperthyroidism ( 2-6 weeks), Transient
hypothyroidism becomes Normal
• Lab = ↑ T3, ↑ T4, ↓ TSH , ↓I 131 uptake ( in Grave’s - ↑ T3, ↑ T4, ↓ TSH , ↑ I
131 uptake)
• 3. Sub acute Lymphatic ( painless) Thyroiditis = Silent Thyroiditis
• Middle aged females with Hyperthyroidism (post partum Thyroiditis)
• Pathogenesis = ? autoimmune
• Thyroiditis contd… .
• 3. Sub acute Lymphatic ( painless) Thyroiditis = Silent Thyroiditis
• Morphology = diffuse painless goiter
• Lymphocytic infiltrate with germinal centers ( unlike Hashimoto’s no
fibrosis or hurthle cell change)
• Lab= ↑ T3, ↑ T4, ↓ TSH
• Clinical course = Hyperthyroidism (unlike Grave’s without skin or ocular
changes)
• Recurrent with subsequent pregnancies
• 4. Riedel’s Thyroiditis
• Unknown etiology
• Extreme fibrosis ( also retroperitoneal)
• Adherent to adjacent tissues
• DD= Carcinoma of thyroid
• 5. palpation Thyroiditis
• Due to vigorous clinical palpation
• Chronic inflammation & giant cells
• Lab = No abnormalities
• Diffuse & Multinodular goiter
• Goiter = enlargement of thyroid
• MC manifestation of thyroid disease
• MCC of Goiter – dietary Iodine deficiency
• 1. Diffuse non –toxic goiter ( Grave’s = diffuse toxic)
• MCC– regions of dietary Iodine deficiency
• Also called endemic goiter
• Morphology = Follicles willed with colloid ( colloid goiter)
• Lab = normal T3 & T4, ↑ TSH
• Clinical = euthyroid,
• 2. Multinodular goiter = develop from diffuse nontoxic goiters
• Clinically = very large goiter ( 2000 mg wt.), painless,
• Produce pressure/ mass effects
• Nodularity = uneven hyperplasia of follicles with hemorrhage, necrosis,
scar
• Lab = Euthyroid, varied I 131 uptake
• Plummer syndrome = euthyroid becomes hyperthyroid ( with grave’s
features)
Multinodular goiter (adenomatous goiter)
•Secondary changes
hemorrhage, fibrosis,
calcification & cystic
degeneration
Calcification
• Neoplasms of thyroid
• STN = solitary thyroid nodule
• More common in female, advanced age,
• How to interpret STN?
• STN in young male = neoplasm
• STN in a person with history of radiation = malignancy
• Hot (increased I 131 uptake) = hyperfunction, not neoplastic
• Cold = decreased I 131 uptake) = 10% malignant
• Lab = Ultrasound or FNAC Biopsy
• Benign neoplasm
• Adenoma = Follicular adenoma
• Discrete, solitary,
• integrity or intact capsule ( extremely important) to differentiate from follicular
carcinoma
• Carcinoma = uncommon in USA
• More common in females, most are well differentiated
Carcinomas of thyroid
Feature Papillary Follicular Medullary Anaplastic
Frequency MC (75-85%) 2nd MC (10- 5% <5%
20%)
Cells Follicular Follicular “C” cells ( Para Follicular
follicular
( calcitonin)
Genetics RET/PTC N RAS RET ( 95% of P53
( chromosome– mutations familial cases inactivation
10) ,MEN II)
Risk factors Radiaion Ultinodular - -
goiter ( Iodine
↓)
Age 20-40 yrs. 40-50 yr 40-50 yr 65 yr
Carcinomas of thyroid
Feature Papillary Follicular Medullary Anaplastic
Morphology Papillae, Malignant cells Amyloid Poorly
psammoma form follicles deposit differentiated,
bodies, orphan with capsular highly
Annie eye like invasion infiltrative
nuclei,( empty
looking),
Prognosis Excellent 50 % Better 100%
95%- 10yr mortality
survival)
1) PAPILLARY CARCINOMA
Nuclear inclusions
Pale nuclei = orphan Annie eyes
2) FOLLICULAR CARCINOMA
3) MEDULLARY CARCINOMA
•MEN-associated (familial):
•Multicentric & bilateral
•Peak 3rd-4th decades
•Amyloid deposits in the stroma
(stroma look pink)
•Staining:
•Positive for calcitonin,