How is lithium-induced diabetes insipidus (DI) managed?

Management of Lithium-Induced Diabetes Insipidus

The primary management of lithium-induced nephrogenic diabetes insipidus (NDI) includes ensuring adequate fluid intake, reducing lithium exposure when possible, and using thiazide diuretics combined with prostaglandin synthesis inhibitors to decrease urine output. 1

Diagnosis Confirmation

Before initiating treatment, confirm the diagnosis:

• Measure serum sodium, serum osmolality, and urine osmolality
• Low urine osmolality (<200 mOsm/kg) with high serum osmolality suggests NDI
• Plasma copeptin levels >21.4 pmol/l in adults are diagnostic for NDI 1

Immediate Management

1. Ensure adequate hydration:

   • Allow ad libitum access to water to prevent dehydration and hypernatremia 1
   • Let patients self-regulate fluid intake based on thirst sensation when possible
   • For patients unable to self-regulate, offer water frequently

2. Lithium management:

   • Consider temporarily suspending lithium during acute illness or before procedures requiring NPO status 2
   • If clinically appropriate, discuss with psychiatry about alternative mood stabilizers
   • If lithium must be continued, aim for lower therapeutic levels (12-hour trough value of 0.4-0.6 mmol/L) 3

Pharmacological Management

For symptomatic patients with significant polyuria (>4L/day), initiate:

1. Thiazide diuretics:

   • Hydrochlorothiazide 25 mg once or twice daily 1
   • Mechanism: Induces mild volume depletion, increases proximal water reabsorption
   • Monitor for hypokalemia and add amiloride if needed 1

2. Prostaglandin synthesis inhibitors:

   • Indomethacin 50 mg three times daily can produce dramatic improvement within hours 4, 5
   • Alternative: Selective COX-2 inhibitor (celecoxib) to reduce gastrointestinal side effects 1
   • Caution: Consider discontinuing in adults due to nephrotoxicity concerns 1

3. Combined therapy:

   • Thiazides + low salt diet + prostaglandin inhibitors provide maximal effect 1
   • Monitor for side effects including hypotension, electrolyte abnormalities

Dietary Modifications

• Recommend low-salt diet to potentiate the efficacy of thiazide diuretics 1
• Ensure adequate caloric intake, especially in children
• Limit protein intake according to age-appropriate guidelines 1

Monitoring

Regular monitoring should include:

• Serum electrolytes (Na, K, Cl, HCO3)
• Renal function (creatinine, eGFR)
• Urine osmolality and 24-hour urine volume
• Ultrasound of the urinary tract every 2-3 years to detect hydronephrosis 1

Special Considerations

• NDI may persist for months to years after lithium discontinuation 6
• Approximately 10% of patients on long-term lithium therapy (15 years) develop NDI 3
• Patients should wear medical alert bracelets and have contact information for specialists 1
• Avoid NSAIDs for pain management as they can increase lithium levels 2

Pitfalls and Caveats

• Drug treatment can cause hyponatremia if fluid intake remains high after starting treatment 1
• Close monitoring of fluid balance, weight, and electrolytes is essential when starting treatment
• Lithium-induced NDI may be only partly reversible upon lithium discontinuation 3
• Indomethacin should be used cautiously in patients with renal impairment or gastrointestinal risk factors

By following this algorithmic approach, lithium-induced NDI can be effectively managed to improve quality of life and prevent complications such as dehydration and hypernatremia.