What is the treatment for Diabetes Insipidus (DI)?

Treatment of Diabetes Insipidus

The treatment for diabetes insipidus depends on the type, with central diabetes insipidus requiring desmopressin (DDAVP) as first-line therapy, while nephrogenic diabetes insipidus requires thiazide diuretics combined with prostaglandin synthesis inhibitors and dietary modifications. 1, 2, 3

Types of Diabetes Insipidus and Their Treatments

Central Diabetes Insipidus (CDI)

• First-line treatment: Desmopressin (DDAVP) - a synthetic analog of antidiuretic hormone (ADH)
• Administration routes:
  • Oral (tablets or sublingual lyophilisate)
  • Intranasal spray
  • Subcutaneous injection (for hospitalized patients or infants)
• Monitoring requirements:
  • Measure serum sodium within 7 days and approximately 1 month after initiating therapy
  • Periodically monitor serum sodium during treatment
  • More frequent monitoring in patients ≥65 years and those at increased risk of hyponatremia 3

Nephrogenic Diabetes Insipidus (NDI)

• First-line treatment: Combination therapy with:
  1. Thiazide diuretics (e.g., hydrochlorothiazide)
  2. Prostaglandin synthesis inhibitors (e.g., celecoxib)
  3. Low-salt diet (≤6 g/day) and low-protein diet (<1 g/kg/day) 1, 2
• Add-on therapy: Amiloride for patients with thiazide-induced hypokalemia 1, 2
• Note: Desmopressin is ineffective and not indicated for nephrogenic diabetes insipidus 3

Treatment Algorithm for Diabetes Insipidus

1. Confirm diagnosis and type of diabetes insipidus

   • Measure serum sodium, serum osmolality, urine osmolality
   • Verify polyuria, polydipsia, and hypernatremic dehydration with inappropriately low urine osmolality
   • Genetic testing for AVPR2 and AQP2 mutations when appropriate 2

2. For Central Diabetes Insipidus:

   • Ensure normal serum sodium before starting treatment
   • Initiate desmopressin therapy with careful dose titration
   • Restrict free water intake to prevent hyponatremia
   • Monitor serum sodium regularly 3

3. For Nephrogenic Diabetes Insipidus:

   • Ensure free access to water at all times
   • Initiate thiazide diuretic therapy
   • Add prostaglandin synthesis inhibitor
   • Implement dietary modifications (low salt, low protein)
   • Add amiloride if hypokalemia develops 1, 2

Special Considerations

For Children with NDI

• Ensure normal-for-age milk intake in infants (instead of water) to guarantee adequate caloric intake
• Consider tube feeding in infants with repeated episodes of vomiting, dehydration, or failure to thrive
• Monitor height and weight every 2-3 months
• Toilet training should proceed as normal, though full continence may only be reached in the second decade of life 1

Emergency Management for NDI

• Each patient should have an emergency plan with a letter explaining their diagnosis
• Use water with dextrose or glucose (e.g., 5% dextrose) for intravenous rehydration
• Calculate initial fluid administration rate to avoid decreasing serum sodium >8 mmol/l/day
• Close monitoring of clinical status, fluid balance, weight, and electrolytes 1

Pregnancy Considerations

• Prostaglandin synthesis inhibitors are contraindicated during pregnancy 1
• For CDI, desmopressin can be used but requires careful monitoring

Monitoring Treatment Efficacy

• For NDI: Evaluate urine osmolality, urine output, weight gain, and growth (in children) 1
• For CDI: Monitor serum sodium, urine volume, and osmolality 3
• Perform kidney ultrasound at least once every 2 years in NDI patients to monitor for urinary tract dilatation 1

Common Pitfalls and Caveats

1. Hyponatremia risk with desmopressin: Severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death. Desmopressin is contraindicated in patients with excessive fluid intake, illnesses causing fluid/electrolyte imbalances, and those using loop diuretics or systemic/inhaled glucocorticoids 3

2. Medication side effects:

   • Thiazide diuretics: Hypokalemia, gout, hypercholesterolemia
   • Prostaglandin synthesis inhibitors: Gastrointestinal bleeding, nephrotoxicity

3. Discontinuation considerations:

   • Prostaglandin synthesis inhibitors should be discontinued once patients reach adulthood or when complete continence is achieved 1
   • If hyponatremia occurs with desmopressin, it may need to be temporarily or permanently discontinued 3

4. Multidisciplinary approach: Patients with NDI should be followed by a team including a nephrologist, dietitian, psychologist, social worker, and urologist 1