A 35-year-old man from Mumbai with Graves' disease has been on methimazole 20 mg daily for 4 months. His TSH is now 2.5 mIU/L and free T4 is 12 pmol/L (normal range). He reports fatigue and weight gain. On examination, he has no signs of hyperthyroidism. What is the most appropriate adjustment to his antithyroid therapy?

Explanation

## Clinical Scenario Analysis This patient has achieved biochemical euthyroidism on methimazole but is experiencing symptoms of **iatrogenic hypothyroidism** (fatigue, weight gain). The TSH is normal but free T4 is at the lower end of normal, suggesting relative overtreatment. ## The Block-and-Replace Strategy **Key Point:** The **block-and-replace (BAR)** regimen is a standard approach in antithyroid therapy. It involves: 1. Continuing the antithyroid drug at a fixed dose to block thyroid hormone synthesis 2. Adding levothyroxine to replace the blocked hormone and maintain euthyroidism 3. Titrating both drugs to maintain TSH and free T4 in the normal range ## Advantages of Block-and-Replace | Aspect | Benefit | |--------|----------| | **Dose stability** | Antithyroid dose remains constant; no need for frequent adjustments | | **Symptom control** | Prevents both hyper- and hypothyroid symptoms | | **Compliance** | Simpler regimen; patient takes fixed doses | | **Outcome** | Superior remission rates in some studies | **High-Yield:** The alternative "titration" strategy (reducing antithyroid dose as TSH rises) is also valid but requires more frequent dose adjustments and monitoring. BAR is preferred when the patient is symptomatic from overtreatment. ## Why NOT the Other Options - **Continuing current dose** (option 0): The patient is symptomatic from relative hypothyroidism; continuing the same dose will perpetuate symptoms. - **Discontinuing methimazole** (option 2): Propranolol alone does not treat the underlying thyroid disorder and will not prevent relapse of hyperthyroidism. - **Increasing methimazole** (option 3): This will worsen hypothyroid symptoms and is contraindicated when TSH is already normal and free T4 is low-normal. **Clinical Pearl:** Fatigue and weight gain in a euthyroid patient on antithyroid therapy should raise suspicion for iatrogenic hypothyroidism. Always check both TSH and free T4 (not TSH alone) to guide therapy adjustments. The goal is to keep both TSH and free T4 in the normal range. [cite:KD Tripathi 8e Ch 42]