A 52-year-old woman from rural India presents with progressive fatigue, weight gain of 8 kg over 6 months, constipation, and dry skin. She reports feeling cold even in warm weather and has noticed thinning of the outer third of her eyebrows. On examination, her pulse is 48 bpm, blood pressure 138/88 mmHg, and skin is cool and dry. Laboratory investigations show: TSH 18.5 mIU/L (normal 0.4–4 mIU/L), free T4 0.8 ng/dL (normal 0.8–1.8 ng/dL), and serum cholesterol 285 mg/dL. What is the most appropriate initial management?

Explanation

## Diagnosis and Rationale **Key Point:** This patient has primary hypothyroidism (elevated TSH with low-normal free T4) presenting with classic clinical features: fatigue, weight gain, cold intolerance, constipation, dry skin, bradycardia, and loss of outer eyebrow hair (madarosis). ## Initial Management Strategy **High-Yield:** Levothyroxine (synthetic T4) is the gold standard first-line therapy for primary hypothyroidism. It is preferred because: - Long half-life (~7 days) allows once-daily dosing - Peripheral conversion to T3 maintains physiologic hormone ratios - Predictable pharmacokinetics with reliable TSH suppression - Cost-effective and widely available ## Dosing Approach in This Patient **Clinical Pearl:** In a middle-aged woman without cardiac disease, starting with a low dose (25 mcg) and titrating gradually is the safest approach because: 1. Avoids sudden increase in metabolic rate and cardiac workload 2. Reduces risk of arrhythmias, angina, or myocardial ischemia in older patients 3. Allows assessment of symptom response before further dose escalation 4. TSH should be rechecked 6–8 weeks after each dose adjustment (time to reach steady state) **Mnemonic:** START LOW, GO SLOW — especially in older or cardiac-risk patients. ## Target and Monitoring | Parameter | Target | Timing | |-----------|--------|--------| | TSH | 0.5–2.5 mIU/L (goal suppression) | Recheck every 6–8 weeks | | Free T4 | Upper-normal range (0.8–1.8 ng/dL) | Once TSH normalized | | Clinical response | Resolution of symptoms | 4–6 weeks | **Tip:** Absorption of levothyroxine is reduced by iron, calcium, PPIs, and some antacids — counsel on timing of administration (empty stomach, 30–60 min before food). [cite:Harrison 21e Ch 405]