What is the treatment for Diabetes Insipidus (DI)?

Treatment of Diabetes Insipidus

Desmopressin is the treatment of choice for central diabetes insipidus, while nephrogenic diabetes insipidus requires thiazide diuretics combined with NSAIDs plus dietary modifications—but all patients with DI must have unrestricted access to water to prevent life-threatening hypernatremia. 1, 2, 3

Distinguish Central from Nephrogenic DI First

Before initiating treatment, you must differentiate between central and nephrogenic forms:

• Measure plasma copeptin levels as the primary differentiating test: levels <21.4 pmol/L indicate central DI, while levels >21.4 pmol/L suggest nephrogenic DI 1, 2
• Initial biochemical work-up should include simultaneous measurement of serum sodium, serum osmolality, and urine osmolality 1, 4
• The diagnostic triad is pathognomonic: polyuria, polydipsia, and inappropriately dilute urine (osmolality <200 mOsm/kg H₂O) with high-normal or elevated serum sodium 1, 2
• For suspected nephrogenic DI, obtain early genetic testing to confirm diagnosis 2, 4

Treatment Algorithm for Central Diabetes Insipidus

Desmopressin is the definitive treatment and can be administered via multiple routes 1, 4, 3:

Dosing Specifics (Intranasal Route)

• Adults: Start with 0.1-0.4 mL daily, with most requiring 0.2 mL daily divided into two doses 3
• Children (3 months to 12 years): Use 0.05-0.3 mL daily, either as single dose or divided into two doses 3
• Adjust morning and evening doses separately to establish adequate diurnal rhythm of water turnover 3
• The nasal spray pump delivers 10 mcg per spray; prime by pressing down 5 times before first use and discard after 50 sprays 3

When Intranasal Route is Compromised

Switch to injectable desmopressin when patients have nasal congestion, nasal discharge, atrophic rhinitis, impaired consciousness, or following transsphenoidal surgery with nasal packing 3

Treatment Algorithm for Nephrogenic Diabetes Insipidus

Nephrogenic DI requires a three-pronged approach: pharmacotherapy, dietary modification, and fluid management 2, 4

Pharmacological Management

• Start combination therapy with thiazide diuretics plus prostaglandin synthesis inhibitors (NSAIDs) for symptomatic infants and children 1, 2
• Thiazides combined with low-salt diet reduce diuresis by up to 50% through mild volume depletion and increased proximal sodium/water reabsorption 2, 4
• Add amiloride if hypokalemia develops from thiazide therapy 2
• NSAIDs enhance collecting duct water permeability but are contraindicated during pregnancy 2, 4
• Consider discontinuing NSAIDs once patients reach adulthood or achieve complete continence 2

Dietary Modifications (Essential Component)

• Restrict salt to ≤6 g/day and protein to <1 g/kg/day to reduce renal osmotic load and minimize urine volume 1, 2
• Provide dietetic counseling to ensure compliance 2
• For infants, maintain normal-for-age milk intake (instead of water) to ensure adequate caloric intake 2
• Consider tube feeding (nasogastric or gastrostomy) for infants with repeated vomiting, dehydration, or failure to thrive 2, 4

Universal Management Principles (All DI Types)

Fluid Management (Critical)

• Patients must have free access to fluid at all times to prevent dehydration, hypernatremia, growth failure, and constipation 1, 2
• Patients capable of self-regulating should determine fluid intake based on thirst sensation rather than prescribed amounts 1, 2, 4
• For patients who cannot self-regulate, offer water frequently 2
• When fasting is required (>4 hours), administer intravenous 5% dextrose in water at maintenance rate with close monitoring 2

Monitoring Requirements

• Assess height and weight regularly, especially in children 2
• Monitor plasma electrolytes (Na, K, Cl, HCO₃, creatinine, osmolality) and urine osmolality 2
• Perform kidney ultrasound at least every 2 years to monitor for urinary tract dilatation or bladder dysfunction from polyuria 2
• Evaluate treatment efficacy via urine osmolality, urine output, weight gain, and growth 2

Emergency Management

• Each patient should carry an emergency plan with a letter explaining their diagnosis and IV fluid management advice 2
• For acute decompensation, use IV rehydration with 5% dextrose 2
• Closely observe clinical status including neurological condition, fluid balance, body weight, and serum electrolytes 2

Critical Pitfalls to Avoid

• Never restrict fluid access in DI patients—this can cause life-threatening hypernatremia and neurologic complications 1, 2
• Desmopressin is ineffective for nephrogenic DI; attempting to use it wastes time and delays appropriate therapy 3
• Avoid overly aggressive desmopressin dosing in central DI, as hyponatremia occurs in one in four patients—allow regular breaks from desmopressin to permit aquaresis 5
• The intranasal spray becomes unreliable after 50 sprays; patients must discard and use a new bottle 3
• In elderly patients, use caution with desmopressin dosing due to decreased renal function and higher risk of toxic reactions 3