A 42-year-old man with bipolar II disorder is started on lithium carbonate. During counselling on adverse effects, the physician discusses the most common endocrine complication. Which of the following is the most common endocrine side effect of lithium?

Explanation

## Lithium and Endocrine Dysfunction **Key Point:** Hypothyroidism is the most common endocrine side effect of lithium, occurring in 20–30% of patients on chronic therapy. ### Mechanism of Lithium-Induced Hypothyroidism 1. Lithium inhibits thyroid peroxidase (TPO) and iodine incorporation 2. Reduces thyroid hormone (T₃ and T₄) synthesis and release 3. Increases thyroid-stimulating hormone (TSH) via feedback 4. May trigger or unmask autoimmune thyroiditis 5. Results in overt or subclinical hypothyroidism **High-Yield:** Lithium-induced hypothyroidism is: - More common in **women** (female-to-male ratio ~3:1) - More frequent with **higher doses** and **longer duration** of therapy - Often **asymptomatic** in early stages (detected by TSH screening) - **Reversible** if lithium is discontinued early, but may persist ### Lithium Endocrine Side Effects Comparison | Endocrine Effect | Frequency | Mechanism | Clinical Significance | |---|---|---|---| | **Hypothyroidism** | 20–30% (most common) | ↓ TPO, ↓ T₃/T₄ synthesis | Requires levothyroxine; TSH monitoring | | **Hyperparathyroidism** | 5–10% | ↑ PTH secretion, ↑ Ca²⁺ reabsorption | Mild hypercalcemia; rarely symptomatic | | **Hyperthyroidism** | < 1% | Rare; thyroiditis | Usually transient | | **Hypogonadism** | Uncommon | Unclear mechanism | Not a primary lithium effect | **Clinical Pearl:** All patients starting lithium should have baseline TSH and free T₄ measured, then monitored every 6–12 months. If hypothyroidism develops, levothyroxine can be added without discontinuing lithium. **Mnemonic:** **LEND** = **L**ithium → **E**ndocrine (Hypothyroidism is the **H**ighest incidence).