Thyroiditis, hypo- and hyperfunctions of the thyroid gland

1. Thyroiditis

Overview

• Inflammation of the thyroid gland.
• Acute form rare; subacute/chronic forms more common.

A) Hashimoto’s Thyroiditis (Chronic Lymphocytic Thyroiditis)

• Most common cause of hypothyroidism in iodine-sufficient areas.
• Autoimmune disease causing hypothyroidism + painless goiter.
• Age 45–65 yr; F >> M.
• Also affects children → major cause of pediatric goiter.

Pathogenesis (3 mechanisms)

• CD4 Th1 → IFN-γ → macrophage activation → thyrocyte cell injury.
• CD8⁺ T-cell mediated direct thyrocyte killing.
• Anti-thyroid antibodies (anti-TPO, anti-thyroglobulin) → NK cell binding → ADCC → cell death.

Morphology

• ↓ Thyroid follicles, replaced by lymphoid follicles with germinal centers + Hurthle (oxyphil) cells.

Associations

• Other autoimmune diseases (T1DM, vitiligo, Addison, SLE).
• ↑ Risk of B-cell non-Hodgkin lymphoma (MALT).
• HLA-DR3/DR5.

B) De Quervain Thyroiditis (Subacute Granulomatous)

• Women 35–50 yr.
• Likely viral or post-viral (Coxsackie, mumps, measles).
• Disruption of follicles → colloid extravasation → granulomatous reaction with giant cells.
• Sx: painful neck, fever, thyroid enlargement.
• Course: starts hyperthyroid (release of preformed hormone) → hypothyroid (destruction) → recovery.
• Self-limited.

C) Riedel Thyroiditis

• Extensive fibrosis of thyroid + surrounding neck structures (rock-hard).
• Antithyroid antibodies present → autoimmune origin (IgG4-related).
• → Hypothyroidism.
• Can mimic carcinoma.

D) Subacute Lymphocytic Thyroiditis (Silent / Painless)

• Postpartum common (postpartum thyroiditis).
• Lymphocytic infiltration + germinal centers.
• Autoimmune (circulating anti-thyroid antibodies).
• Painless neck mass; middle-aged women.

2. Goiter

Definition

• Enlargement of thyroid gland.

Types

• Diffuse symmetric: usually TSH-induced; follicles like Graves disease.
• Multinodular irregular: develops from long-standing diffuse goiter → may become toxic (Plummer disease).

Pathogenesis

• Dietary iodine deficiency = #1 cause:
  • Impairs T3/T4 synthesis → ↑ TSH → follicular hypertrophy + hyperplasia → enlargement.

Causes

• Endemic: iodine-poor regions.
• Sporadic: F > M, peak puberty / young adult (↑ T4 demand); goitrogens (cabbage, cauliflower, turnips), Ca²⁺.

3. Hypothyroidism

Definition

• Insufficient thyroid hormone production/release.

Causes

• Primary (intrinsic gland abnormality):
  • Hashimoto thyroiditis (#1 in iodine-sufficient areas).
  • Iodine deficiency (#1 worldwide).
  • Drugs, surgery (thyroidectomy), radiation.
• Secondary (extrinsic): pituitary / hypothalamic failure.

Clinical Manifestations

Cretinism

• Congenital hypothyroidism.
• Causes: maternal iodine deficiency, enzyme defect.
• Features: impaired skeletal development + CNS (mental retardation), short stature, coarse facies, umbilical hernia.

Myxedema (adults)

• Generalized apathy + mental sluggishness + cold intolerance + obesity.
• Non-pitting edema (mucopolysaccharide accumulation):
  • Broadening of facial features.
  • Enlarged tongue (macroglossia).
  • Deepening of voice.
• Bradycardia, decreased bowel motility (constipation), dry skin, hair loss.

Diagnosis

• Primary: ↑ TSH + ↓ T4 (free).
• Secondary: ↓ TSH + ↓ T4.

4. Hyperthyroidism

Definition

• Excess thyroid hormone release.
• Thyrotoxicosis = hypermetabolic state from ↑ free T3 + T4.

Clinical Manifestations of Thyrotoxicosis

• Skin: soft, warm, flushed; heat intolerance + sweating.
• GI: hypermotility, malabsorption, diarrhea.
• Cardiac: palpitations + tachycardia (atrial fibrillation in elderly).
• Neuropsychiatric: nervousness, tremor, irritability, insomnia.
• Eye: wide, staring gaze (sympathetic overstimulation of levator palpebrae superioris).
• Weight loss despite ↑ appetite.
• Osteoporosis.

Diagnosis

• ↑ T3, T4 + ↓ TSH (primary).

5. Graves-Basedow Disease

Overview

• #1 cause of hyperthyroidism.
• Autoimmune; F >> M; HLA-DR3 association.

Classic Triad

1. Thyrotoxicosis with diffuse hyperfunctional goiter.
2. Infiltrative ophthalmopathy → exophthalmos.
3. Pretibial myxedema (non-pitting infiltrative dermopathy).

Pathogenesis (anti-TSH receptor antibodies)

• Thyroid-stimulating Ig (TSI): binds TSH receptor → hormone release.
• Thyroid growth-stimulating Ig: → follicular epithelium proliferation.
• TSH-binding inhibitor Ig: blocks TSH binding (can mimic or inhibit).

Morphology

• Diffuse thyroid enlargement.
• Histology: colloid depletion + papillae formation by follicular epithelium projecting into lumen.
• Extrathyroidal: generalized lymphoid hyperplasia; ophthalmopathy from edematous orbital tissues displacing eyeball.

Clinical + Labs

• ↑ Free T3 + T4, ↓ TSH.
• Exophthalmos, lid lag, pretibial myxedema.
• Tx: antithyroid drugs (methimazole, PTU), radioactive iodine, surgery; β-blockers for Sx.

6. Quick Comparison — Thyroid Function Tests

Condition	TSH	Free T4	Antibodies
Hashimoto	↑	↓	Anti-TPO, anti-Tg
Graves	↓	↑↑	TSI (anti-TSHR)
De Quervain	↓ then ↑	↑ then ↓	—
Subacute lymphocytic	Varies	Varies	Anti-TPO
Riedel	↑	↓	IgG4
Secondary hypothyroidism	↓	↓	—

💡 High-yield: Hashimoto = #1 hypothyroidism (iodine-sufficient); anti-TPO/anti-Tg; lymphoid follicles + Hurthle cells; ↑ MALT lymphoma. De Quervain = painful, post-viral, granulomas; hyper → hypo → recovery; self-limited. Riedel = rock-hard fibrosis, mimics cancer. Subacute lymphocytic = postpartum, painless. Goiter = #1 iodine deficiency. Cretinism = congenital hypothyroidism (mental retardation + dwarfism). Myxedema = non-pitting + macroglossia + cold intolerance. Graves disease = #1 hyperthyroidism, TSI antibodies, triad: diffuse goiter + exophthalmos + pretibial myxedema, ↑ T3/T4 + ↓ TSH.