Subacute Granulomatous Thyroiditis (de Quervain)

Pathogenesis and clinical phases: 1) Viral etiology - postulated to follow viral upper respiratory infection by 2-8 weeks; commonly implicated viruses include mumps, coxsackievirus, adenovirus, influenza, Epstein-Barr virus, measles, mumps, COVID-19; HLA-Bw35 in 70% suggests genetic susceptibility; 2) Histopathology - characteristic giant cell granulomas with multinucleated giant cells engulfing colloid; lymphocytic infiltration; follicle disruption with release of preformed thyroid hormone; later fibrosis; histology rarely needed for diagnosis; 3) Phase 1 - Thyrotoxic phase (weeks 1-6) - inflammation destroys follicles, releasing preformed T4 and T3; transient hyperthyroidism with palpitations, tremor, heat intolerance, weight loss, anxiety; symptoms typically less severe than Graves disease; 4) Phase 2 - Euthyroid transition (weeks 4-12) - hormone stores depleted; TSH still suppressed; 5) Phase 3 - Hypothyroid phase (weeks 8-20) - hormone synthesis impaired; symptoms of hypothyroidism with fatigue, cold intolerance, dry skin, constipation; 50-60% develop biochemical hypothyroidism, 25% symptomatic; 6) Phase 4 - Recovery (>3 months) - 80-95% return to euthyroidism within 12-18 months; 5-15% develop permanent hypothyroidism requiring lifelong levothyroxine; 7) Recurrence - 1-4% experience recurrence months to years later, sometimes after viral illness.

Clinical presentation and diagnosis: 1) Symptoms - sudden or gradual onset over days; severe pain in anterior neck, often radiating to jaw or ears, exacerbated by swallowing or head movement; constitutional symptoms (fever 38-40°C, malaise, fatigue, sweating, myalgia, anorexia, weight loss); thyrotoxic symptoms (palpitations, tremor, heat intolerance) in 50%; sometimes preceded by URI; 2) Examination - exquisitely tender enlarged thyroid (usually diffuse, sometimes asymmetric or unilateral with subsequent contralateral involvement - 'creeping thyroiditis'); cervical lymphadenopathy variable; tachycardia, tremor in thyrotoxic phase; 3) Laboratory - elevated ESR (often >50 mm/hr, sometimes >100 mm/hr - hallmark) and CRP; mild leukocytosis; mild anemia; thyroid function shows phase-dependent pattern - thyrotoxic phase: low TSH, high free T4/T3, high T4/T3 ratio (>20:1) due to preformed hormone release; euthyroid then hypothyroid; thyroglobulin elevated; thyroid antibodies usually negative or low titer; 4) Imaging - radioiodine uptake (RAIU) characteristically low (<5% at 24 hours), differentiating from Graves disease; ultrasound shows hypoechoic ill-defined patchy areas (geographic), reduced vascularity (vs increased in Graves); CT/MRI not routinely needed; 5) Differential diagnosis - acute suppurative thyroiditis (more severely ill, neutrophilic, distinct), thyroid cancer (less acute, painless usually), Hashimoto thyroiditis (chronic, painless), Graves disease (high RAIU, vascularity), painful Hashimoto, hemorrhage into nodule.

Treatment and follow-up: 1) Mild disease (low pain, no severe symptoms) - NSAIDs (ibuprofen 400-800 mg q6-8h, naproxen 500 mg twice daily) for 2-8 weeks; symptoms improve in 1-2 weeks; 2) Moderate to severe disease (severe pain, NSAID failure, debilitating symptoms) - oral prednisone 40 mg/day for 1-2 weeks then tapered over 4-6 weeks; rapid relief of pain (24-48 hours); shortens disease course in some studies but does not change long-term thyroid outcome; recurrence on tapering may require slower taper or restart; 3) Thyrotoxic phase management - beta-blockers (propranolol 20-40 mg three times daily) for symptomatic palpitations and tremor; antithyroid drugs not effective (no hormone synthesis to inhibit); 4) Hypothyroid phase - levothyroxine 25-50 mcg/day if symptomatic or TSH >10 mIU/L; usually needed only for 6-12 months as recovery occurs; 5) Monitoring - clinical and biochemical (TSH, free T4) every 4-6 weeks during disease, then every 3-6 months for first year, then annually; ESR normalizes over weeks; 6) Patient education - reassure about self-limiting nature; symptoms often dramatic but resolve completely in most; warning signs of permanent hypothyroidism (persistent fatigue, weight gain, cold intolerance) need check-up; 7) Special considerations - pregnant patients managed similarly with adjustment of NSAIDs and corticosteroids; postpartum thyroiditis is a separate entity (painless); COVID-19-associated subacute thyroiditis emerging post-pandemic, similar treatment.