What is the primary treatment for diabetes insipidus?

Treatment of Diabetes Insipidus

Central Diabetes Insipidus

Desmopressin is the treatment of choice for central diabetes insipidus and should be initiated after confirming normal serum sodium levels. 1, 2, 3

Desmopressin Administration Routes and Dosing

• Oral melt tablets are the preferred formulation at 120-240 μg per dose, offering better bioavailability than traditional tablets 4
• Intranasal administration at 2.5-15 μg twice daily provides excellent control in most patients 5
• Subcutaneous administration is reserved for infants or patients with postoperative/posttraumatic brain injury requiring close monitoring 6

Critical Dosing Principles

• Adjust doses separately for morning and evening to establish adequate diurnal rhythm, monitoring urine volume intermittently rather than prescribing fixed amounts 4
• Patients should titrate to the minimal effective dose that prevents excessive polyuria, particularly at night 6, 5
• Evening fluid intake must be limited to 200 mL or less with no drinking until morning to prevent water intoxication and hyponatremia 4

Mandatory Monitoring Protocol

• Ensure serum sodium is normal before starting or resuming desmopressin 2
• Measure serum sodium within 7 days, at 1 month after initiation, and periodically thereafter 2
• Monitor more frequently in patients ≥65 years and those at increased risk of hyponatremia 2
• Assess urine volume and osmolality intermittently during treatment 2

Critical Safety Warning

Desmopressin is contraindicated in patients with excessive fluid intake, illnesses causing fluid/electrolyte imbalances, and those using loop diuretics or systemic/inhaled glucocorticoids due to severe hyponatremia risk. 2 If hyponatremia develops, desmopressin may require temporary or permanent discontinuation 2.

Nephrogenic Diabetes Insipidus

For symptomatic infants and children with nephrogenic diabetes insipidus, initiate combination therapy with thiazide diuretics and prostaglandin synthesis inhibitors (NSAIDs). 7, 1, 8

Pharmacological Treatment

• Thiazide diuretics combined with low-salt diet (≤6 g/day) reduce diuresis by up to 50% in the short term through mild volume depletion and increased proximal sodium/water reabsorption 7, 8
• Add amiloride if hypokalemia develops during thiazide therapy 8
• Prostaglandin synthesis inhibitors enhance collecting duct water permeability and should be added to the regimen 1, 8
• Prostaglandin synthesis inhibitors are contraindicated during pregnancy and should be considered for discontinuation once patients reach adulthood or achieve complete continence 8

Dietary Management

• Implement low salt (≤6 g/day) and protein (<1 g/kg/day) diet with dietetic counseling to reduce renal osmotic load 8
• For infants, provide normal-for-age milk intake instead of water to ensure adequate caloric intake 7, 8
• Space oral feeds and fluids carefully to reduce vomiting from gastroesophageal reflux exacerbated by large fluid volumes 7

Tube Feeding Considerations

• Consider tube feeding (nasogastric or gastrostomy) for repeated vomiting/dehydration episodes or growth failure, though this is rarely continued beyond 4 years of age 7, 8
• Approximately 20-30% of children with nephrogenic diabetes insipidus receive tube feeding at some point 7

Critical Monitoring at Treatment Initiation

Close monitoring of fluid balance, weight, and biochemistry is essential when starting drug treatment, as marked hyponatremia can occur if patients maintain unchanged high fluid intake after commencing therapy 7.

Universal Management Principles (Both Types)

Fluid Access

Free access to fluid is essential in all patients with diabetes insipidus to prevent dehydration, hypernatremia, growth failure, and constipation. 1, 8

• Patients capable of self-regulating should determine fluid intake based on thirst sensation rather than prescribed amounts 1, 8
• Those unable to self-regulate should be offered water frequently 8

Fasting Protocols

• When fasting >4 hours is required, administer intravenous 5% dextrose in water at maintenance rate with close monitoring 8

Diagnostic Approach

• Suspect diabetes insipidus in patients with polyuria, polydipsia, and inappropriately dilute urine (osmolality <200 mOsm/kg H₂O) with high-normal or elevated serum sodium 1, 8
• Initial work-up requires measuring serum sodium, serum osmolality, and urine osmolality 7, 1
• Plasma copeptin levels distinguish types: <21.4 pmol/L indicates central diabetes insipidus, while >21.4 pmol/L suggests nephrogenic diabetes insipidus 1, 8

Genetic Testing for Nephrogenic Diabetes Insipidus

• Perform early genetic testing in suspected nephrogenic diabetes insipidus cases to avoid harmful diagnostic procedures like water deprivation tests 7, 1
• Test all symptomatic females and male offspring of known AVPR2 mutation carriers 7
• Use umbilical cord blood for genetic testing in male offspring of heterozygote carriers directly after birth 7
• Approximately 90% of cases are X-linked (AVPR2 mutations), while <10% are autosomal (AQP2 mutations) 7

Ongoing Monitoring

• Regularly assess height and weight, especially in children 8
• Monitor serum electrolytes (Na, K, Cl, HCO₃), creatinine, and osmolality 8
• Perform kidney ultrasound at least every 2 years to monitor for urinary tract dilatation and bladder dysfunction 8

Emergency Management

Each patient with nephrogenic diabetes insipidus should have an emergency plan including a letter explaining their diagnosis with intravenous fluid management advice. 8 Use intravenous 5% dextrose for rehydration with close observation of neurological status, fluid balance, weight, and serum electrolytes 8.