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Differential Diagnosis of Thyroiditis

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Overview Table

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1. Hashimoto Thyroiditis (Chronic Autoimmune Thyroiditis)

• Most common cause of hypothyroidism in iodine-sufficient areas
• Female predominance 10:1 to 20:1; peak age 45-65 years
• Pathogenesis: Breakdown of self-tolerance to thyroid autoantigens; CD8+ cytotoxic T cells, Th1 cytokines (IFN-gamma), and anti-TPO/anti-thyroglobulin antibodies all contribute to follicular destruction
• Genetics: CTLA4, PTPN22, IL2RA polymorphisms increase susceptibility
• Morphology: Diffusely enlarged pale firm gland; lymphoplasmacytic infiltrate + germinal centers; oncocytic (Hurthle cell) metaplasia of follicular epithelium; variable fibrosis
• Labs: Anti-TPO and anti-thyroglobulin antibodies elevated in >90%; eventually high TSH, low free T4
• Clinical: Goiter (initially), then gradual gland atrophy; associated with other autoimmune conditions (T1DM, vitiligo, pernicious anemia, Sjogren's)
• Complications: Small increased risk of B-cell lymphoma of the thyroid; possible progression to hypothyroid crisis
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 998-999

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2. Subacute Granulomatous Thyroiditis (De Quervain Thyroiditis / Painful Thyroiditis)

• Probably viral in origin (preceded by upper respiratory infection - Coxsackie, mumps, influenza, adenovirus)
• More common in females; peak age 30-50 years
• Triphasic course:
  1. Thyrotoxic phase (1-3 months): released preformed hormone
  2. Hypothyroid phase: depleted stores
  3. Recovery to euthyroidism (in most patients)
• Key feature: PAINFUL thyroid - severe neck pain often radiating to jaw/ear, may be systemic (fever, malaise)
• Labs: Very low RAIU (hallmark), elevated ESR (often >50 mm/hr), elevated free T4/T3, suppressed TSH; anti-TPO usually absent or low
• Morphology: Granulomatous inflammation with foreign-body giant cells engulfing colloid
• Treatment: NSAIDs for pain; corticosteroids if severe; beta-blockers for symptoms; thyroxine replacement if hypothyroid phase prolonged
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 999-1000

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3. Silent (Painless) Thyroiditis and Postpartum Thyroiditis

• Autoimmune variants - essentially the same disease; postpartum thyroiditis is silent thyroiditis occurring within 12 months of delivery
• Postpartum incidence ~10% of pregnancies; higher risk with anti-TPO positivity in first trimester
• Clinical: PAINLESS goiter; same triphasic hyper → hypo → recovery pattern as de Quervain, but milder
• ~25% experience only thyrotoxic phase; ~50% experience only hypothyroid phase
• Labs: Low RAIU during toxic phase (T3:T4 ratio <20, unlike Graves where T3 preferentially elevated); anti-TPO positive; TSH receptor antibodies NEGATIVE (distinguishes from Graves)
• Doppler ultrasound: Markedly decreased flow (vs. increased flow in Graves)
• Prognosis: ~25% develop permanent hypothyroidism; recurrence in subsequent pregnancies is common
• Goldman-Cecil Medicine, p. 2440

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4. Riedel (Sclerosing) Thyroiditis

• Rare - accounts for ~1 in 100,000 thyroid surgeries
• Often associated with IgG4-related disease (can involve salivary/lacrimal glands, bile ducts, retroperitoneum, mediastinum)
• Clinical: Painless, rock-hard "woody" goiter; may compress trachea/esophagus causing dysphagia, stridor; may invade surrounding structures (unlike carcinoma, it is benign but fibrotic)
• Labs: Usually hypothyroid; elevated IgG4 levels in associated cases
• Distinguished from anaplastic carcinoma by biopsy showing dense fibrosis without malignant cells
• Treatment: Tamoxifen, corticosteroids; surgical decompression if trachea compromised
• Goldman-Cecil Medicine, p. 2441

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5. Acute Suppurative (Infectious) Thyroiditis

• Rare - bacterial (Staph. aureus, Strep., anaerobes), fungal, or parasitic
• Predisposing factors: immunocompromised state, piriform sinus fistula (in children), preexisting thyroid disease
• Clinical: Acute onset severe pain, fever, tenderness, fluctuance; surrounding erythema; thyroid usually euthyroid
• Diagnosis: FNA with Gram stain and culture; ultrasound shows abscess
• Treatment: IV antibiotics + surgical drainage

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6. Drug-Induced Thyroiditis

• Key point: even a single dose of an immune checkpoint inhibitor can trigger autoimmune thyroid dysfunction
• Amiodarone-induced thyrotoxicosis is the hardest to treat; if type 1 vs type 2 cannot be distinguished, treat both simultaneously (methimazole + prednisone)
• Goldman-Cecil Medicine, p. 2440-2441

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Key Distinguishing Points for Boards/Clinic

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• Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 998-1000
• Robbins & Kumar Basic Pathology, pp. 998-999
• Goldman-Cecil Medicine (International Edition), pp. 2440-2441