A 42-year-old man on lithium for bipolar I disorder develops coarse tremor, polydipsia, polyuria, hypothyroidism, and a serum lithium of 0.9 mEq/L (therapeutic). Which mechanism explains the lithium-induced hypothyroidism?

• A Enhancement of TSH receptor sensitivity
• B Direct destruction of follicular cells via oxidative stress
• C Induction of anti-thyroglobulin antibodies
• D Inhibition of thyroid peroxidase and reduction of iodine organification ✓

Explanation

Lithium inhibits thyroid hormone synthesis by interfering with iodine organification and coupling reactions (inhibits thyroid peroxidase activity), and also inhibits the release of T3/T4 from thyroglobulin. It can trigger or worsen autoimmune thyroiditis in predisposed individuals. The result is increased TSH and goitre; hypothyroidism occurs in 20–40% of long-term users. Thyroid function should be checked every 6 months in lithium-treated patients; levothyroxine supplementation can be added without discontinuing lithium.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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