What is diabetes insipidus and how is it managed?

Diabetes Insipidus: Definition and Management

Diabetes insipidus (DI) is a condition characterized by polyuria, polydipsia, and inappropriately dilute urine (urine osmolality <200 mOsm/kg H₂O) due to either deficiency of antidiuretic hormone (central DI) or resistance to its action in the kidneys (nephrogenic DI). 1, 2

Types of Diabetes Insipidus

• Central Diabetes Insipidus (CDI): Caused by inadequate production or secretion of antidiuretic hormone (ADH/vasopressin) from the posterior pituitary gland 2
• Nephrogenic Diabetes Insipidus (NDI): Caused by kidney resistance to ADH action, often due to mutations in AVPR2 or AQP2 genes 3, 1
• Dipsogenic DI: Characterized by excessive thirst due to a low osmotic threshold 2
• Gestational DI: Occurs during pregnancy due to increased concentration of placental vasopressinase 2

Diagnosis

Initial Evaluation

• Suspect DI in patients with polyuria, polydipsia, failure to thrive, and hypernatremic dehydration with inappropriately dilute urine (osmolality <200 mOsm/kg H₂O) 3, 1
• Measure serum sodium, serum osmolality, and urine osmolality as initial biochemical work-up 3, 1
• Plasma copeptin levels help distinguish between different types of DI:

  • 21.4 pmol/l suggests nephrogenic DI

  • <21.4 pmol/l suggests central DI 1, 4

Confirmatory Testing

• Response to desmopressin administration is diagnostic:
  • Central DI shows positive response (decreased urine output, increased urine osmolality)
  • Nephrogenic DI shows no response 5, 4
• Early genetic testing is recommended for suspected NDI, particularly testing of AVPR2 and AQP2 genes 3, 1

Management

Central Diabetes Insipidus

1. Pharmacological Treatment:

   • Desmopressin (synthetic ADH analog) is the first-line treatment 5, 6
   • Available as nasal spray, oral tablets, or injection 6
   • Nasal spray dosage: 10 mcg per spray (0.1 mL of 0.01% solution), typically 1-2 sprays 1-3 times daily 6
   • Pediatric dosing should start at lower doses (0.05 mL or less) 6

2. Monitoring:

   • Regular assessment of urine volume, urine osmolality, and serum sodium 1, 5
   • Watch for hyponatremia, the main complication of desmopressin treatment 6
   • Efficacy can be monitored by decreased urine volume and increased urine osmolality 6

3. Precautions:

   • Use with caution in patients with coronary artery insufficiency, hypertension, fluid/electrolyte imbalances, and renal disorders 6
   • Nasal route may be inappropriate with nasal congestion, discharge, mucosal atrophy, or impaired consciousness 6

Nephrogenic Diabetes Insipidus

1. Fluid Management:

   • Free access to fluid is essential to prevent dehydration, hypernatremia, and growth failure 1
   • Patients capable of self-regulating should determine their fluid intake based on thirst 1
   • For infants, normal-for-age milk intake (instead of water) is recommended to ensure adequate caloric intake 3, 1

2. Dietary Modifications:

   • Low salt (≤6 g/day) and protein diet (<1 g/kg/day) to reduce renal osmotic load 1
   • Support from a dietitian experienced with NDI is recommended 3

3. Pharmacological Treatment:

   • Thiazide diuretics combined with low-salt diet can reduce diuresis by up to 50% in the short term 3, 1
   • Prostaglandin synthesis inhibitors (NSAIDs) can be added to thiazides 3
   • Add amiloride for patients who develop hypokalemia from thiazides 3, 1
   • Note: Desmopressin is ineffective for nephrogenic DI 6

4. Special Considerations for Infants:

   • Consider tube feeding (nasogastric or gastrostomy) for infants with repeated vomiting, dehydration, or growth failure 3, 1
   • Careful spacing of oral feeds and fluid may reduce vomiting problems 3

Emergency Management

• Each patient should have an emergency plan including advice on intravenous fluid management 1
• For fasting >4 hours, provide intravenous 5% dextrose in water at maintenance rate 1
• Intravenous rehydration with water and dextrose (e.g., 5% dextrose) is recommended for emergency situations 1
• Close monitoring of clinical status, fluid balance, body weight, and serum electrolytes is essential 1

Long-term Monitoring

• Regular assessment of height and weight, especially in children 1
• Monitor basic plasma (Na, K, Cl, HCO₃, creatinine, osmolality) and urine biochemistry 1
• Kidney ultrasound every 2 years to check for urinary tract dilatation or bladder dysfunction 1, 4
• Be aware that response to treatment may change over time, with some patients showing decreased responsiveness or shortened duration of effect 6