What is the treatment for diabetes insipidus?

Treatment of Diabetes Insipidus

The treatment of diabetes insipidus depends on the specific type, with desmopressin being the first-line therapy for central diabetes insipidus, while nephrogenic diabetes insipidus requires thiazide diuretics, NSAIDs, and amiloride, along with dietary modifications and unrestricted fluid access. 1, 2

Types of Diabetes Insipidus

Diabetes insipidus (DI) is a disorder characterized by excessive urination (polyuria) and excessive thirst (polydipsia) due to problems with antidiuretic hormone (ADH, also called vasopressin). There are two main types:

1. Central (Cranial) Diabetes Insipidus

   • Caused by insufficient production of ADH from the posterior pituitary
   • May result from head trauma, surgery, tumors, or infiltrative diseases affecting the pituitary region
   • Recently proposed to be renamed "vasopressin deficiency" 3

2. Nephrogenic Diabetes Insipidus

   • Caused by kidney resistance to ADH
   • Can be genetic (mutations in AVPR2 or AQP2 genes) or acquired (often from medications like lithium)
   • Recently proposed to be renamed "vasopressin resistance" 3

Diagnosis

Before initiating treatment, proper diagnosis is essential:

• Laboratory assessment: Measure serum sodium, serum osmolality, and urine osmolality 1
• Water deprivation test: Gold standard test followed by desmopressin administration 4
• Copeptin measurement: Emerging as a promising surrogate marker for ADH 4
• Genetic testing: For suspected nephrogenic DI, focusing on AVPR2 (X-linked, 90% of cases) and AQP2 (autosomal forms, <10% of cases) 1

Treatment of Central Diabetes Insipidus

1. Desmopressin (DDAVP)

   • First-line therapy as antidiuretic replacement 2
   • Available as injection, nasal spray, or oral tablets
   • Dosing:
     • Initial dose: 2-4 mcg daily administered as one or two divided doses by subcutaneous or intravenous injection
     • Adjust based on adequate duration of sleep and appropriate water turnover 2

2. Monitoring

   • Assess serum sodium before starting treatment and within 7 days and 1 month after initiating therapy
   • Monitor for hyponatremia, which can be life-threatening
   • Restrict free water intake during treatment 2

3. Precautions

   • Contraindicated in patients at increased risk of severe hyponatremia
   • Use caution in elderly patients and those with cardiovascular or renal disease 2

Treatment of Nephrogenic Diabetes Insipidus

1. First-line combination therapy 1

   • Thiazide diuretics
   • Prostaglandin synthesis inhibitors (NSAIDs)
   • Amiloride (particularly effective for lithium-induced NDI)

2. Dietary modifications 1

   • Low-salt diet (<6 g/day or 2.4 g sodium)
   • Low-protein diet (<1 g/kg/day)
   • Adequate caloric intake

3. Fluid management

   • Unrestricted access to water/fluids
   • Allow self-regulation based on thirst
   • For infants: normal-for-age milk intake instead of water 1

4. Important note: Desmopressin is ineffective and not indicated for nephrogenic diabetes insipidus 2

Monitoring and Follow-up

1. Regular blood tests (every 3-12 months, more frequent in children) 1

   • Electrolytes
   • Renal function
   • Uric acid levels

2. Ultrasound monitoring of urinary tract every 2-3 years to detect:

   • Hydronephrosis
   • Bladder wall hypertrophy
   • Post-micturition residue 1

3. Growth monitoring in children 1

Emergency Management

1. Fluid administration rates to prevent rapid changes in serum sodium: 1

   • Adults: 25-30 mL/kg/24h
   • Children (first 10 kg): 100 ml/kg/24h
   • Children (10-20 kg): 50 ml/kg/24h
   • Children (remaining): 20 ml/kg/24h

2. Hypernatremia correction

   • Limit to <8 mmol/L/day to prevent osmotic demyelination syndrome 1
   • Hospitalization may require specialized fluid management with 5% dextrose

Special Considerations

1. Genetic counseling for affected individuals and carriers 1

2. Long-term complications without proper management:

   • Chronic kidney disease (in approximately 50% of adult patients)
   • Urinary tract pathology
   • Growth failure in children
   • Potential neurodevelopmental issues 1

3. Quality of life considerations

   • Patients with central DI may have altered quality of life possibly due to oxytocin deficiency 3
   • Lifelong management is required for both types of DI 1