A 32-year-old woman presents with a 3-week history of progressive fatigue, weight gain, and cold intolerance. She reports a painful, tender swelling in the anterior neck that worsened over the past 10 days. On examination, the thyroid is firm, enlarged, and exquisitely tender to palpation. Laboratory investigations show TSH 8.2 mIU/L (normal 0.4–4.0), free T4 2.8 ng/dL (normal 0.8–1.8), and elevated ESR of 65 mm/hr. Thyroid peroxidase (TPO) antibodies are negative. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Subacute Granulomatous Thyroiditis ### Key Clinical Features **Key Point:** Subacute granulomatous thyroiditis (also called De Quervain thyroiditis or viral thyroiditis) is characterized by the triad of: 1. Painful, tender thyroid enlargement 2. Systemic inflammation (elevated ESR, fever) 3. Transient thyroid dysfunction with negative autoantibodies ### Pathophysiology This condition follows a viral prodrome (often URI or viral exanthem) and is thought to be immune-mediated. Histology shows granulomatous inflammation with multinucleate giant cells and disrupted follicles. ### Clinical Timeline in This Case - **3-week progressive fatigue** → hypothyroid phase (elevated TSH, low-normal T4) - **Painful, tender swelling** → acute inflammatory phase - **Elevated ESR (65 mm/hr)** → systemic inflammation - **Negative TPO antibodies** → rules out autoimmune thyroiditis ### Differential Features | Feature | Subacute Granulomatous | Hashimoto | Acute Suppurative | Riedel | | --- | --- | --- | --- | --- | | **Pain** | Severe, tender | Painless | Severe, localized abscess | Painless, hard | | **ESR** | Markedly elevated (>50) | Normal/mildly elevated | Elevated | Normal/mild | | **Antibodies** | Negative | TPO/Tg positive | None | None | | **Fever** | Common | Absent | High fever, septic | Absent | | **Bacterial culture** | Negative | N/A | Positive | N/A | | **Histology** | Granulomas, giant cells | Lymphocytic infiltration | Abscess formation | Fibrosis | **High-Yield:** The combination of **severe pain + tender thyroid + markedly elevated ESR + negative antibodies** is pathognomonic for subacute granulomatous thyroiditis. ### Clinical Course Subacute thyroiditis typically follows a triphasic pattern: 1. **Thyrotoxic phase** (1–3 weeks): Release of preformed hormone → low TSH, high T4 2. **Hypothyroid phase** (weeks 3–6): Depletion of stored hormone → high TSH, low T4 (this patient is here) 3. **Recovery phase** (weeks 6–12): Restoration of normal thyroid function **Clinical Pearl:** Unlike Graves disease (thyrotoxicosis with negative RAIU) or thyroiditis-induced thyrotoxicosis, the radioiodine uptake in subacute thyroiditis is **suppressed** due to inflammation and follicular disruption, not increased hormone synthesis. ### Management - NSAIDs (ibuprofen 400–600 mg TID) for pain and inflammation - Corticosteroids (prednisone 40–60 mg/day tapered over 6–8 weeks) if severe or refractory - Beta-blockers for symptomatic thyrotoxicosis during early phase - Levothyroxine only during hypothyroid phase if TSH markedly elevated [cite:Robbins 10e Ch 24]