Lithium Carbonate Causes Diabetes Insipidus
Lithium carbonate is the medication most likely to cause diabetes insipidus among the options listed. The other medications—metformin, lisinopril, amlodipine, and atorvastatin—are not associated with causing diabetes insipidus 1, 2.
Mechanism and Incidence
Lithium causes nephrogenic diabetes insipidus (NDI) by making the kidneys unresponsive to antidiuretic hormone, resulting in the inability to concentrate urine 1, 2.
Approximately 10% of patients on long-term lithium therapy (≥15 years) develop NDI, making it the most common cause of drug-induced diabetes insipidus 2.
The FDA drug label explicitly warns that chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia 1.
Clinical Presentation
Patients present with polyuria (often >4 L/day) and polydipsia 2, 3.
Laboratory findings include elevated serum sodium, elevated serum osmolality, low urine osmolality (<300 mOsm/kg), and low urine specific gravity 3.
The condition is usually reversible when lithium is discontinued, though in patients treated long-term it appears to be only partly reversible 1, 2.
Diagnostic Approach
Measure urinary concentrating capacity during a 12-hour water deprivation test or administer desmopressin to demonstrate renal unresponsiveness 2.
In nephrogenic DI (most common with lithium), desmopressin administration results in <50% increase in urine osmolality 3.
Consider central diabetes insipidus as well, as rare cases have been documented with lithium use where desmopressin produces >50% increase in urine osmolality 3.
Management Strategy
Stop lithium if possible and switch to alternative mood stabilizers 2.
If lithium must be continued and urine volumes exceed 4 L/day, initiate thiazide diuretics (e.g., hydrochlorothiazide) plus amiloride 2, 4.
Add NSAIDs (e.g., indomethacin) in severe cases for additional antidiuretic effect 2, 4.
Desmopressin can reduce urine output by approximately 70% when added to thiazides and NSAIDs in lithium-induced NDI, though its efficacy as monotherapy is limited 4.
Prevention
Monitor 12-hour trough lithium levels targeting 0.4-0.6 mmol/L in long-term users 2.
Measure 24-hour urine volume yearly to detect early NDI development 2.
Carefully manage patients to avoid dehydration, which can lead to lithium retention and toxicity 1.
Critical Pitfall
Serum lithium levels and clinical findings do not always correlate—patients can develop NDI even with therapeutic or subtherapeutic lithium levels 5, 3. The diagnosis is based on clinical presentation and urinary concentrating defects, not solely on lithium levels.
Why Other Medications Don't Cause DI
Metformin is associated with lactic acidosis risk, not diabetes insipidus 6.
Lisinopril and amlodipine are antihypertensives with no association to diabetes insipidus 6.
Atorvastatin has been studied as a potential treatment for lithium-induced NDI but showed no significant benefit and does not cause DI 7.