Lithium-Induced Nephrogenic Diabetes Insipidus
The most likely cause of this patient's symptoms is lithium-induced nephrogenic diabetes insipidus, given the combination of polyuria, polydipsia, nocturia, low urine specific gravity (<1.010), hypernatremia, and chronic lithium therapy for bipolar disorder. 1
Clinical Reasoning
Key Diagnostic Features Present
Polyuria with dilute urine: The afternoon urine specific gravity less than 1.010 indicates the kidneys are producing large volumes of dilute urine despite likely dehydration 2, 3
Polydipsia and nocturia: These symptoms represent the body's compensatory mechanism to maintain fluid balance in the setting of excessive urinary water loss 2, 4
Hypernatremia: The elevated serum sodium level confirms inadequate water retention relative to solute, consistent with diabetes insipidus 2, 5
Chronic lithium exposure: Lithium is the most common drug cause of nephrogenic diabetes insipidus, and the patient has been on lithium therapy for an extended period 1, 2
Why Lithium-Induced NDI is Most Likely
Lithium causes renal insensitivity to antidiuretic hormone (ADH) by interfering with aquaporin-2 channel function in the collecting ducts, resulting in the kidney's inability to concentrate urine despite adequate ADH secretion 2, 5. The European Association of Urology specifically identifies lithium as a key medication to review when evaluating nocturia and polyuria, listing it alongside diuretics and NSAIDs as important drug causes 1.
Excluding Other Differential Diagnoses
Type 2 diabetes mellitus: While family history is positive, the HbA1c is normal, making uncontrolled diabetes mellitus unlikely as the primary cause 1, 3
Central diabetes insipidus: Would present similarly but is less likely given the clear medication exposure to lithium 2, 4
Primary polydipsia: Would typically show some ability to concentrate urine and normal sodium levels, unlike this case 4, 6
Obstructive sleep apnea: While OSA can cause nocturia, it would not explain the daytime polyuria, polydipsia, hypernatremia, or persistently dilute urine 7
Recommended Diagnostic Approach
Immediate Next Steps
Morning urine osmolality after overnight fluid restriction: Concentrations remaining below 600 mOsm/L despite fluid restriction confirm diabetes insipidus 1, 5
Plasma ADH level: Elevated or normal levels in the setting of dilute urine and hypernatremia confirm nephrogenic (rather than central) diabetes insipidus 4, 5
Water deprivation test: This test will show persistent inability to concentrate urine, with urine specific gravity and osmolality remaining low despite rising plasma osmolality 2, 3
Additional Baseline Investigations
The European Association of Urology recommends comprehensive evaluation including electrolytes/renal function (already showing hypernatremia), thyroid function, calcium, and assessment for other SCREeN conditions (Sleep, Cardiovascular, Renal, Endocrine, Neurology) 1, 8.
Management Considerations
Lithium Management
The primary intervention requires coordination with psychiatry to evaluate whether lithium can be discontinued or switched to an alternative mood stabilizer, as continued lithium exposure will perpetuate the nephrogenic diabetes insipidus 2, 5. The European Urology guidelines emphasize that medication review is crucial, particularly for drugs like lithium that directly cause symptoms 1.
Symptomatic Treatment if Lithium Must Continue
Thiazide diuretics: Paradoxically reduce urine output in nephrogenic diabetes insipidus by causing mild volume depletion, which enhances proximal tubule sodium and water reabsorption 2, 5
Amiloride: May be particularly useful in lithium-induced NDI as it blocks lithium entry into collecting duct cells 2, 5
Adequate hydration: Essential to prevent severe dehydration and hypernatremia 2, 5
Common Pitfalls to Avoid
Assuming diabetes mellitus is the cause: The normal HbA1c and persistently low urine specific gravity despite likely glucosuria (if present) should prompt consideration of diabetes insipidus 3
Failing to recognize medication-induced causes: The European Urology guidelines specifically warn against overlooking lithium as a cause of polyuria and nocturia 1, 8
Not coordinating with psychiatry: Abrupt lithium discontinuation without psychiatric input risks bipolar disorder relapse 1
Inadequate monitoring: Patients require close monitoring of electrolytes, renal function, and fluid balance to prevent life-threatening hypernatremia 2, 5