What is the primary treatment for managing diabetes insipidus?

Management of Diabetes Insipidus

The primary treatment for diabetes insipidus depends on the type, with desmopressin being the first-line therapy for central diabetes insipidus, while thiazide diuretics combined with prostaglandin synthesis inhibitors are recommended for nephrogenic diabetes insipidus. 1, 2

Types of Diabetes Insipidus and Diagnosis

• Diabetes insipidus should be suspected in patients presenting with polyuria, polydipsia, and inappropriately dilute urine (urine osmolality <200 mOsm/kg H₂O) with high-normal or elevated serum sodium 1
• Initial biochemical work-up should include serum sodium, serum osmolality, and urine osmolality 1, 3
• Plasma copeptin levels can help distinguish between different types:
  • Levels >21.4 pmol/l suggest nephrogenic diabetes insipidus 1
  • Levels <21.4 pmol/l indicate central diabetes insipidus 1
• Early genetic testing is strongly recommended for suspected nephrogenic diabetes insipidus to confirm diagnosis 3, 1

Treatment of Central Diabetes Insipidus

Pharmacological Management

• Desmopressin (DDAVP) is the first-line treatment for central diabetes insipidus 2, 4
• Available formulations include:
  • Oral tablets or sublingual lyophilisate (which provides better bioavailability) 4, 5
  • Intranasal spray 4, 6
  • Injectable form for subcutaneous administration (particularly useful in postoperative settings) 2, 4
• Dosing is highly individualized, with patients typically finding their effective minimal dose to maintain normal life without excessive polyuria 4
• When converting from nasal to oral formulations, a median dose conversion factor of approximately 20:1 is typically used 6

Monitoring and Safety Considerations

• Desmopressin can cause hyponatremia, which can be life-threatening 2, 7
• Before starting treatment:
  • Assess baseline serum sodium, urine volume, and osmolality 2
  • Ensure normal serum sodium before initiating therapy 2
• During treatment:
  • Measure serum sodium within 7 days and approximately 1 month after initiating therapy 2
  • Implement fluid restriction to prevent water intoxication 2, 7
  • More frequent monitoring is needed for patients ≥65 years and those at increased risk of hyponatremia 2
• If hyponatremia occurs, desmopressin may need to be temporarily or permanently discontinued 2

Treatment of Nephrogenic Diabetes Insipidus

Fluid Management

• Free access to fluid is essential to prevent dehydration, hypernatremia, growth failure, and constipation 3, 1
• Patients capable of self-regulating should determine their fluid intake based on thirst sensation 1
• When fasting is required (>4h), intravenous 5% dextrose in water at maintenance rate with close monitoring is recommended 1, 8

Dietary Modifications

• A low salt (≤6 g/day) and protein diet (<1 g/kg/day) is recommended to reduce renal osmotic load and minimize urine volume 3, 1
• For infants with NDI, normal-for-age milk intake (instead of water) is recommended to ensure adequate caloric intake 3, 1
• Tube feeding should be considered in infants and children with repeated episodes of vomiting, dehydration, and/or failure to thrive 3, 1

Pharmacological Treatment

• Thiazide diuretics combined with prostaglandin synthesis inhibitors (NSAIDs) are the mainstay of treatment for nephrogenic diabetes insipidus 3, 1
• Thiazides act by inducing mild volume depletion and can reduce diuresis by up to 50% in the short term when combined with a low-salt diet 3, 1
• Amiloride should be added to thiazide in patients who develop hypokalemia 1
• NSAIDs are contraindicated during pregnancy and should be used with caution in patients with renal impairment 1, 8
• Desmopressin is ineffective and not indicated for the treatment of nephrogenic diabetes insipidus 2

Monitoring and Follow-up

• Regular assessment of height and weight, especially in children 1
• Monitoring of basic plasma biochemistry (Na, K, Cl, HCO₃, creatinine, osmolality) and urine osmolality 1
• Kidney ultrasound should be performed at least once every 2 years to monitor for urinary tract dilatation and/or bladder dysfunction caused by polyuria 3, 1
• Each patient with diabetes insipidus should have an emergency plan, including a letter explaining their diagnosis with advice regarding intravenous fluid management 1, 8

Emergency Management

• For intravenous rehydration, use water and dextrose or glucose (e.g., 5% dextrose) 1
• Close observation of clinical status, including neurological condition, fluid balance, body weight, and serum electrolytes is essential 1, 8
• Consider placement of a urinary catheter to ensure proper monitoring of diuresis in acute settings 8