A 52-year-old man with a 10-year history of multinodular goiter presents with acute onset of palpitations, dyspnea, and tremor over 2 days. He denies recent iodine exposure or medication changes. On examination, temperature is 38.2°C, heart rate 124 bpm, and he has a firm, tender, enlarged thyroid with multiple palpable nodules. Laboratory results: TSH < 0.01 mIU/L, free T4 22 pg/dL (normal 0.8–1.8), free T3 8.1 pg/mL (normal 2.3–4.2), radioiodine uptake is low (2%, normal 10–30%), and inflammatory markers (ESR 68 mm/hr, CRP 12 mg/dL) are elevated. Which of the following is the most likely diagnosis?

Explanation

## Diagnosis: Subacute Thyroiditis Superimposed on Toxic Multinodular Goiter ### Clinical Presentation Analysis **Key Point:** This case combines two distinct pathologies: 1. **Pre-existing toxic multinodular goiter** (10-year history, multiple palpable nodules) 2. **Acute subacute thyroiditis** (fever, thyroid tenderness, elevated inflammatory markers, acute symptom onset) ### Distinguishing Features | Feature | Subacute Thyroiditis | Graves' Disease | Toxic MNG | |---------|----------------------|-----------------|----------| | **Onset** | Acute (days) | Gradual (weeks) | Gradual (months–years) | | **Fever & Tenderness** | Yes (prominent) | No | No | | **Inflammatory markers** | Elevated (ESR, CRP) | Normal | Normal | | **Radioiodine uptake** | **Low/suppressed** | Diffuse ↑ | Nodular ↑ | | **Thyroid nodules** | Absent | Absent (diffuse) | Multiple | | **Antibodies** | Negative | TRAb positive | Negative | **High-Yield:** The **low radioiodine uptake (2%)** is the key discriminator. In thyroiditis, elevated T3/T4 results from **release of pre-formed hormone from damaged follicles**, not synthesis. The thyroid is "too inflamed to take up iodine." In contrast, Graves' and toxic MNG show increased uptake because the thyroid is actively synthesizing hormone. ### Pathophysiology of Subacute Thyroiditis ```mermaid flowchart TD A[Viral infection or autoimmune trigger]:::outcome --> B[Thyroid follicular destruction]:::action B --> C[Release of pre-formed T3/T4 into circulation]:::action C --> D[Elevated free T3/T4 + suppressed TSH]:::outcome B --> E[Inflammatory infiltrate & thyroid pain]:::action E --> F[Fever, tenderness, elevated ESR/CRP]:::outcome B --> G[Damaged follicles cannot concentrate iodine]:::action G --> H[Low radioiodine uptake]:::outcome ``` **Clinical Pearl:** Subacute thyroiditis typically follows an **upper respiratory viral illness** by 1–2 weeks (though not always evident in history). The condition is **self-limited**, lasting 4–12 weeks, with a triphasic course: thyrotoxic phase → hypothyroid phase → recovery. ### Why This Patient Has Both Conditions The patient's **pre-existing multinodular goiter** (likely toxic MNG) was previously compensated. The superimposed acute viral thyroiditis triggered acute follicular destruction, releasing massive amounts of stored hormone and causing acute thyrotoxicosis with fever and tenderness—a clinical emergency. ### Management Approach **Key Point:** Treatment differs from Graves' disease: - **Antithyroid drugs (PTU/methimazole) are NOT indicated**—the thyroid is not synthesizing excess hormone; it is releasing stored hormone. - **Beta-blockers** for symptom control - **NSAIDs or corticosteroids** for inflammation (if severe) - **Supportive care** and monitoring for progression to hypothyroidism - Address the underlying toxic MNG once acute phase resolves (radioiodine or surgery) **Warning:** Giving antithyroid drugs in thyroiditis is ineffective and delays recovery. The radioiodine uptake test is essential to guide therapy. [cite:Harrison 21e Ch 405]