Diagnostic Finding in Lithium-Induced Nephrogenic Diabetes Insipidus
The correct answer is D: Failure of the kidneys to respond to desmopressin. This is the pathognomonic finding in nephrogenic diabetes insipidus (NDI), which distinguishes it from central diabetes insipidus 1.
Pathophysiology of Lithium-Induced NDI
Nephrogenic diabetes insipidus is characterized by insensitivity of the distal nephron to arginine vasopressin (antidiuretic hormone), resulting in the kidney's inability to concentrate urine despite normal or elevated vasopressin levels 2. Chronic lithium therapy is associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus with polyuria and polydipsia 3.
Why Each Answer is Correct or Incorrect
Option D (Correct): Failure to Respond to Desmopressin
- Response to desmopressin administration is the key diagnostic test: NDI patients show minimal or no response (typically <50% increase in urine osmolality), while central diabetes insipidus patients show a positive response 1.
- Patients with NDI will show little or no increase in urine osmolality when administered aqueous vasopressin or desmopressin, confirming renal unresponsiveness 4.
- This distinguishes NDI from central diabetes insipidus, where desmopressin effectively increases urine concentration 1.
Option A (Incorrect): High Urine Osmolality Despite Polyuria
- The opposite is true in NDI: patients have inappropriately dilute urine (typically <200 mOsm/kg H₂O) despite polyuria 2.
- The diagnosis of NDI is based on demonstrating inappropriately dilute urine in the presence of normal or elevated serum osmolality 2.
- Patients with NDI will have a urinary osmolality of less than 300 mOsm/kg H₂O despite water deprivation 4.
Option B (Incorrect): Normal or Low Plasma Osmolality
- NDI patients typically present with elevated plasma osmolality and hypernatremia when decompensated, as in this clinical scenario 2.
- The typical emergency in NDI is hypernatremic dehydration because of excessive water loss and/or inability to maintain adequate fluid intake 5.
- Both NDI and central diabetes insipidus present with increased plasma osmolality 1.
Option C (Incorrect): Decreased Urine Output with Elevated Sodium Levels
- NDI is characterized by polyuria (increased urine output), not decreased urine output 2.
- The hallmark symptoms of NDI include polyuria and polydipsia, which develop as compensatory mechanisms 2.
- Patients with NDI typically have urine volumes that can exceed 4 L/day 6.
Clinical Context of This Patient
This patient with chronic lithium use presenting with dehydration and hypernatremia represents a decompensated state where the normal compensatory mechanism (polydipsia) has failed 7. Lithium-induced NDI affects approximately 10% of patients treated long-term (≥15 years) and may be only partly reversible upon lithium discontinuation 6. The condition can persist for years even after lithium cessation 8.
Important Clinical Caveat
While nephrogenic diabetes insipidus is the most common form of diabetes insipidus associated with lithium use, rare cases of central diabetes insipidus have been documented with chronic lithium therapy 9. However, given the clinical presentation and the question stem specifically stating "nephrogenic diabetes insipidus," the failure to respond to desmopressin remains the defining diagnostic feature 1, 4.