A 38-year-old woman with bipolar disorder has been on lithium 900 mg daily for 6 months with good mood stabilization. She now presents with polyuria, polydipsia, and nocturia. Which investigation is most appropriate to confirm the suspected diagnosis of lithium-induced nephrogenic diabetes insipidus?

Explanation

## Diagnosis of Lithium-Induced Nephrogenic Diabetes Insipidus ### Clinical Context Lithium-induced nephrogenic diabetes insipidus (NDI) is a well-recognized adverse effect occurring in 20–40% of patients on chronic lithium therapy. The polyuria, polydipsia, and nocturia in this patient are classic presenting symptoms. ### Why Water Deprivation Test + Desmopressin Challenge? **Key Point:** The water deprivation test followed by desmopressin challenge is the gold-standard diagnostic test to differentiate nephrogenic from central diabetes insipidus. **High-Yield:** - **In central DI:** Urine osmolality increases with desmopressin (kidneys respond to ADH). - **In nephrogenic DI (lithium-induced):** Urine osmolality remains low even after desmopressin administration (kidneys are resistant to ADH). ### Test Sequence | Phase | Finding in Nephrogenic DI | |-------|---------------------------| | Baseline | Polyuria, low urine osmolality (<300 mOsm/kg) | | After water deprivation | Urine osmolality remains low (<300 mOsm/kg) | | After desmopressin | Urine osmolality does NOT increase (hallmark of nephrogenic DI) | **Clinical Pearl:** Lithium causes NDI by blocking aquaporin-2 water channels in the collecting duct, rendering the kidney unresponsive to ADH. ### Why Not the Other Options? **Serum lithium level** — Useful to monitor for toxicity, but does not diagnose NDI. Therapeutic levels are 0.6–1.2 mEq/L; NDI can occur even within therapeutic range. **24-hour urine osmolality** — Provides supportive evidence of polyuria but is not diagnostic. Cannot differentiate nephrogenic from central DI without the desmopressin challenge. **Renal ultrasound** — May show structural changes (cysts, atrophy) in chronic lithium use but is not diagnostic for NDI and does not establish the functional defect.