What is the treatment for diabetes insipidus?

Treatment of Diabetes Insipidus

The treatment of diabetes insipidus depends on its type, with desmopressin being the first-line therapy for central diabetes insipidus, while nephrogenic diabetes insipidus requires thiazide diuretics, prostaglandin synthesis inhibitors, and dietary modifications. 1, 2

Types of Diabetes Insipidus

• Diabetes insipidus (DI) should be suspected in patients with polyuria, polydipsia, and inappropriately dilute urine (urine osmolality <200 mOsm/kg H₂O) with high-normal or elevated serum sodium 2
• The two main types are:
  • Central (neurogenic) DI: caused by deficiency in antidiuretic hormone (ADH)
  • Nephrogenic DI: caused by kidney resistance to ADH action 3, 2

Treatment of Central Diabetes Insipidus

First-line Treatment: Desmopressin

• Desmopressin (DDAVP), a synthetic analog of vasopressin, is the treatment of choice for central DI 1, 4
• Available formulations include:
  • Oral melt tablets (120-240 μg per dose)
  • Intranasal spray
  • Injectable form (subcutaneous or intravenous) 1, 4
• For treatment-naïve patients, the recommended starting daily dosage is 2-4 mcg administered as one or two divided doses by subcutaneous or intravenous injection 4
• For patients changing from intranasal desmopressin, the recommended starting dose is 1/10th the daily maintenance intranasal dose 4

Monitoring and Safety Considerations

• Ensure normal serum sodium before starting desmopressin 4
• Monitor serum sodium within 7 days and approximately 1 month after initiating therapy, then periodically during treatment 4
• More frequent monitoring is needed for patients over 65 years and those at increased risk of hyponatremia 4
• Limit evening fluid intake to 200 ml or less with no drinking until morning to prevent water intoxication and hyponatremia 1
• Adjust dose based on adequate duration of sleep and adequate but not excessive water turnover 1, 4

Treatment of Nephrogenic Diabetes Insipidus

Fluid Management

• Free access to fluid is essential to prevent dehydration, hypernatremia, growth failure, and constipation 2
• Patients capable of self-regulating should determine their fluid intake based on thirst sensation 3
• When fasting is required (>4h), intravenous 5% dextrose in water at maintenance rate with close monitoring is recommended 2

Dietary Modifications

• Low salt (≤6 g/day) and protein diet (<1 g/kg/day) with dietetic counseling to reduce renal osmotic load 2
• For infants with NDI, normal-for-age milk intake (instead of water) is recommended to ensure adequate caloric intake 3
• Consider tube feeding for infants and children with repeated episodes of vomiting, dehydration, and/or failure to thrive 3

Pharmacological Treatment

• Thiazide diuretics and prostaglandin synthesis inhibitors are the mainstay of treatment for nephrogenic DI 3, 2
• Thiazide diuretics act by inducing mild volume depletion and can reduce diuresis by up to 50% in the short term when combined with a low-salt diet 3
• Add amiloride to thiazide in patients who develop hypokalemia 3
• Prostaglandin synthesis inhibitors (NSAIDs or selective COX-2 inhibitors) can enhance collecting duct water permeability 2, 5
• Close monitoring of fluid balance, weight, and biochemistry is recommended at the start of treatment 3

Special Considerations

Lithium-Induced Nephrogenic DI

• Regular monitoring of serum electrolytes, kidney function, and urine osmolality is essential 5
• Avoid medications that can worsen renal function during periods of illness 5
• Maintain ad libitum access to fluids at all times to prevent dehydration 5

Emergency Management

• Each patient with DI should have an emergency plan, including a letter explaining their diagnosis with advice regarding intravenous fluid management 2
• For acute management of dehydration, use intravenous rehydration with water and dextrose (e.g., 5% dextrose) 2
• Close observation of clinical status, including neurological condition, fluid balance, body weight, and serum electrolytes is crucial 2

Common Pitfalls and Caveats

• Hyponatremia is the major complication of desmopressin therapy and can lead to seizures, coma, respiratory arrest, or death 4, 6
• Desmopressin is contraindicated in patients at increased risk of severe hyponatremia, such as those with excessive fluid intake, illnesses causing fluid/electrolyte imbalances, and those using loop diuretics or systemic/inhaled glucocorticoids 4
• Desmopressin is ineffective and not indicated for nephrogenic diabetes insipidus 4
• Drug treatment for nephrogenic DI can be very effective in infancy but may lead to marked hyponatremia if high fluid intake is maintained after starting treatment 3