A 35-year-old woman from rural India presents with a firm, diffuse goitre and hypothyroidism. On investigation, her thyroid peroxidase (TPO) antibodies are negative, and urinary iodine is 45 µg/L (normal >100 µg/L). What is the most common cause of her hypothyroidism?

Explanation

## Most Common Cause of Hypothyroidism Globally **Key Point:** Iodine deficiency remains the most common *preventable* cause of hypothyroidism worldwide, and the most common cause of goitre globally [cite:Harrison 21e Ch 405]. ### Clinical Reasoning in This Case The patient presents with: - Firm, diffuse goitre (not nodular) - Hypothyroidism - **Negative TPO antibodies** (rules out autoimmune thyroiditis) - **Low urinary iodine** (45 µg/L vs normal >100 µg/L) - Rural India demographics (endemic iodine deficiency region) These findings are pathognomonic for iodine deficiency disorder (IDD). ### Pathophysiology of Iodine Deficiency 1. Insufficient iodine → reduced thyroid hormone synthesis 2. Low T~3~/T~4~ → loss of negative feedback 3. Elevated TSH → thyroid hyperplasia (goitre formation) 4. Persistent deficiency → hypothyroidism despite goitre **High-Yield:** In iodine deficiency, the goitre is a *compensatory* response; it does not prevent hypothyroidism if deficiency is severe. ### Epidemiology | Cause | Prevalence (Global) | Prevalence (India) | Antibody Status | |-------|---------------------|-------------------|------------------| | **Iodine deficiency** | ~30% of population at risk | ~10–15% in endemic areas | Negative | | Hashimoto's thyroiditis | Most common in iodine-sufficient regions | ~2–3% | TPO/Thyroglobulin positive | | Pituitary/hypothalamic disease | <5% of hypothyroidism | Rare | TSH low/normal | | Dyshormonogenesis | <1% of congenital hypothyroidism | Rare | TSH elevated | **Clinical Pearl:** Urinary iodine <50 µg/L indicates iodine deficiency at the population level; <20 µg/L indicates severe deficiency [cite:KD Tripathi 8e Ch 31].