Q2 LONG ANSWER 10M ★ High-yield

Classify thyroid disorders. Describe Graves disease, Hashimoto thyroiditis and the carcinomas of the thyroid.

Pathology · 2nd Professional — Para-Clinical

Classification of Thyroid Disease

Group	Disorders
Hyperfunction	Graves disease, toxic multinodular goitre, toxic adenoma, thyroiditis (transient)
Hypofunction	Hashimoto thyroiditis, iodine deficiency, iatrogenic (surgery, radioiodine, drugs), congenital
Inflammation	Hashimoto, de Quervain (subacute granulomatous), Riedel, acute suppurative, silent/postpartum
Enlargement	Diffuse and multinodular goitre
Neoplasm	Follicular adenoma; papillary, follicular, medullary and anaplastic carcinoma; lymphoma

Graves Disease

The commonest cause of hyperthyroidism; women aged 20 to 40; female to male ratio 7:1
An autoimmune type II hypersensitivity in which the antibody stimulates — thyroid-stimulating immunoglobulin binds the TSH receptor and mimics TSH, but is not subject to negative feedback
The classical triad — hyperthyroidism with a diffuse goitre, infiltrative ophthalmopathy with exophthalmos, and pretibial myxoedema
Morphology — diffusely enlarged, beefy red gland; tall crowded follicular cells with papillary infoldings, and "scalloped" colloid at the periphery where it is being resorbed; lymphoid aggregates
Ophthalmopathy is caused by a separate mechanism — autoantibodies against retro-orbital fibroblasts cause glycosaminoglycan deposition, oedema and fibrosis of the extraocular muscles, so it does not resolve when the thyroid is treated
Laboratory — TSH suppressed, free T4 and T3 raised, TSH receptor antibody positive, and diffuse increased uptake on isotope scan

Hashimoto Thyroiditis

The commonest cause of hypothyroidism where iodine intake is adequate; women aged 45 to 65; female to male ratio 10:1 to 20:1
Autoimmune destruction by type IV cell-mediated injury with cytotoxic T cells, plus antibody-dependent cytotoxicity
Antibodies — anti-thyroid peroxidase (anti-TPO, the most sensitive) and anti-thyroglobulin
Morphology — diffusely enlarged, firm, pale gland; dense lymphocytic infiltrate with germinal centres, atrophic follicles, and hurthle (Askanazy) cells — follicular cells with abundant granular eosinophilic cytoplasm packed with mitochondria
May pass through a transient thyrotoxic phase ("hashitoxicosis") as stored hormone is released from damaged follicles, before hypothyroidism supervenes
Associations — other autoimmune disease (type 1 diabetes, pernicious anaemia, Addison, vitiligo); a small but real increased risk of thyroid lymphoma

CLINICAL PEARL

Graves and Hashimoto are the same immunological accident with opposite results. Both are autoimmune, both target the thyroid, and both may occur in the same family. In Graves the antibody stimulates the TSH receptor; in Hashimoto cell-mediated injury destroys the gland. Stating that contrast first makes the rest of the comparison follow.

Other Thyroiditis and Goitre

Condition	Features
DE quervain (subacute granulomatous) thyroiditis	Follows a viral upper respiratory infection; a painful, tender gland with fever; granulomas around damaged follicles with giant cells; raised ESR; transient thyrotoxicosis then hypothyroidism then recovery; low isotope uptake
Subacute lymphocytic (silent, postpartum) thyroiditis	Painless; within a year of delivery; lymphocytic infiltrate without germinal centres; usually self-limiting
RIEDEL thyroiditis	Rare; dense fibrosis extending beyond the capsule into surrounding structures, producing a stony-hard gland that mimics carcinoma; part of the IgG4-related disease spectrum
Diffuse and multinodular goitre	Impaired hormone synthesis, most often iodine deficiency, raises TSH and causes hyperplasia; alternating hyperplasia and involution produce nodularity, haemorrhage, fibrosis and calcification. May become toxic (Plummer syndrome) or cause pressure symptoms

A painful thyroid with low isotope uptake and a high ESR is de Quervain thyroiditis; low uptake with thyrotoxicosis is the key to distinguishing it from Graves disease, where uptake is high
Endemic goitre from iodine deficiency was formerly widespread in the sub-Himalayan belt of India, and universal salt iodisation has greatly reduced it — one of the country’s major public health successes

Thyroid Carcinoma

Type	Share	Features	Spread and prognosis
Papillary	75–85%	"ORPHAN ANNIE eye" nuclei — optically clear, ground-glass; nuclear grooves and intranuclear pseudo-inclusions; psammoma bodies; papillae with fibrovascular cores. Associated with radiation exposure and BRAF/RET rearrangement	Lymphatic spread to cervical nodes; excellent prognosis, over 95% at 10 years, even with nodal disease
Follicular	10–20%	Uniform follicles; diagnosis requires capsular or vascular invasion, which is why FNAC cannot distinguish it from a follicular adenoma. Commoner in iodine-deficient areas	Haematogenous spread to bone and lung; good but less favourable
Medullary	About 5%	Arises from parafollicular C cells; secretes calcitonin; sheets of polygonal cells in an amyloid stroma (Congo red positive). About 20% are familial, with RET mutation, as part of men 2A and 2B	Both lymphatic and haematogenous; intermediate prognosis
Anaplastic	Under 5%	Elderly; often on a background of long-standing goitre or differentiated carcinoma; wildly pleomorphic giant and spindle cells	Rapidly fatal — median survival a few months; presents with a rapidly enlarging mass, hoarseness and stridor

Comparison of the Two Autoimmune Thyroid Diseases

Feature	Graves disease	Hashimoto thyroiditis
Functional state	HYPERthyroid	HYPOthyroid (after a possible transient toxic phase)
Mechanism	Type II hypersensitivity — stimulating antibody to the TSH receptor	Type IV cell-mediated destruction plus antibody
Antibodies	TSH receptor antibody (thyroid-stimulating immunoglobulin)	Anti-TPO and anti-thyroglobulin
Gland	Diffusely enlarged, soft, beefy red and vascular, with a bruit	Diffusely enlarged, firm, pale, rubbery
Histology	Tall crowded cells with papillary infoldings; scalloped colloid	Lymphocytes with germinal centres; hurthle cells; atrophic follicles
Isotope uptake	High and diffuse	Low or patchy
Eye signs	Exophthalmos and ophthalmoplegia (infiltrative)	Absent (lid lag only if transiently toxic)
Long-term risk	Relapse; hypothyroidism after treatment	Thyroid lymphoma (small but real)

Applied Aspects

FNAC is the investigation of choice for a thyroid nodule, and reliably diagnoses papillary, medullary and anaplastic carcinoma — but cannot distinguish follicular adenoma from follicular carcinoma, which requires examination of the capsule in a resected specimen
Features suggesting malignancy in a nodule — a solitary hard fixed nodule, rapid growth, hoarseness, cervical lymphadenopathy, previous neck irradiation, age under 20 or over 60, and male sex
A "cold" nodule on isotope scanning carries a higher risk of malignancy than a hot one, though most cold nodules are still benign
Serum calcitonin is the tumour marker for medullary carcinoma, and thyroglobulin is used to detect recurrence of differentiated carcinoma after total thyroidectomy
Screen relatives for RET mutation when medullary carcinoma is diagnosed; prophylactic thyroidectomy is offered to carriers, and phaeochromocytoma must be excluded before any surgery in men 2
Thyroid function tests in India must be interpreted with care in pregnancy, where reference ranges differ and untreated hypothyroidism impairs fetal neurodevelopment
Papillary carcinoma may present as a cervical lymph node with an impalpable primary, and nodal metastasis does not worsen the excellent prognosis appreciably
Radioiodine ablation after total thyroidectomy destroys residual thyroid tissue and allows thyroglobulin to be used as a sensitive marker of recurrence
Anaplastic carcinoma is not curable, and treatment is directed at securing the airway and palliating symptoms rather than at cure

All questions in Endocrine, Bone & Breast Pathology

Every Pathology chapter →