A 32-year-old woman presents with palpitations, tremor, and heat intolerance for 3 weeks. Examination reveals a diffuse goitre, lid lag, and thyroid bruit. TSH is suppressed at 0.01 mIU/L (normal 0.4–4.0), free T4 is elevated at 28 pmol/L (normal 10–20), and free T3 is 8.5 pmol/L (normal 3.5–6.5). Anti-TPO and anti-thyroglobulin antibodies are negative. Technetium-99m thyroid uptake is uniformly increased. What is the most appropriate next step in management?

Explanation

## Clinical Diagnosis **Key Point:** This patient has Graves' disease (diffuse goitre, lid lag, thyroid bruit, uniformly increased uptake on technetium scan, negative antibodies against TPO/thyroglobulin, and biochemical hyperthyroidism). ## Management Strategy for Graves' Disease ### Immediate Priorities **High-Yield:** The immediate goals are: 1. Control thyroid hormone excess and prevent thyroid storm 2. Achieve euthyroid state before definitive therapy (radioactive iodine or surgery) 3. Prevent agranulocytosis and hepatotoxicity with appropriate antithyroid drug choice ### Why PTU Is First-Line in Acute Hyperthyroidism | Feature | PTU | Methimazole | |---------|-----|-------------| | **Onset of action** | Faster (blocks synthesis + peripheral conversion of T4→T3) | Slower (synthesis only) | | **Agranulocytosis risk** | ~0.1–0.3% | ~0.01–0.05% | | **Hepatotoxicity** | Mild, reversible | Rare but severe (fulminant hepatitis) | | **Pregnancy** | Preferred (less teratogenic) | Contraindicated (methimazole embryopathy) | | **Dose** | 300–600 mg/day in divided doses | 30–60 mg/day in divided doses | | **Use in acute/severe** | **Yes — first-line** | Avoid in acute phase | **Clinical Pearl:** PTU's dual action (inhibition of thyroid peroxidase AND inhibition of peripheral deiodinase) makes it superior in acute, symptomatic hyperthyroidism because it reduces circulating T3 faster than methimazole alone. ### Correct Management Sequence ```mermaid flowchart TD A[Confirmed Graves' disease<br/>Symptomatic hyperthyroidism]:::outcome --> B[Start PTU 300 mg TDS<br/>+ Beta-blocker for symptom relief]:::action B --> C[Achieve euthyroid state<br/>4–8 weeks]:::action C --> D{Definitive therapy plan}:::decision D -->|Radioactive iodine| E[Refer endocrinology<br/>Plan RAI after PTU washout]:::action D -->|Surgery| F[Refer endocrinology<br/>Plan thyroidectomy]:::action D -->|Long-term ATD| G[Continue PTU or switch<br/>to methimazole]:::action ``` **Key Point:** Beta-blockers (propranolol) address adrenergic symptoms but do NOT treat the underlying thyroid hormone excess—they are adjunctive only. ## Why This Approach 1. **PTU 300 mg TDS** rapidly blocks thyroid hormone synthesis and peripheral conversion, reducing free T3 within days 2. **Endocrinology referral** ensures proper planning of definitive therapy (RAI vs. surgery) after achieving euthyroid state 3. **Avoids premature RAI** without first controlling the hypermetabolic state and preventing thyroid storm risk 4. **Prevents complications** (agranulocytosis monitoring, hepatic function checks) through specialist oversight