What is diabetes insipidus?

Diabetes Insipidus: Diagnosis and Management

Diabetes insipidus (DI) is a disorder characterized by excessive urination and thirst due to the body's inability to properly regulate water balance, resulting from either deficient antidiuretic hormone (vasopressin) production or kidney resistance to its effects. 1, 2

Types of Diabetes Insipidus

There are two main types of diabetes insipidus:

1. Central (Neurogenic) Diabetes Insipidus

   • Caused by inadequate production or secretion of antidiuretic hormone (ADH/vasopressin) from the posterior pituitary gland
   • Recently proposed to be renamed "vasopressin deficiency" to avoid confusion with diabetes mellitus 2
   • May result from head trauma, surgery in the pituitary region, tumors, or can be idiopathic

2. Nephrogenic Diabetes Insipidus

   • Caused by kidney resistance to the effects of vasopressin
   • Recently proposed to be renamed "vasopressin resistance" 2
   • May be inherited or acquired (medications, electrolyte disorders, kidney disease)

Less common variants include:

• Gestational Diabetes Insipidus: Due to degradation of vasopressin by placental enzymes 3
• Adipsic Diabetes Insipidus: A rare form of central DI characterized by absence of thirst sensation, increasing risk of dehydration and hypernatremia 4

Clinical Presentation

Patients with diabetes insipidus typically present with:

• Polyuria (excessive urination): Often 3-20 liters per day
• Polydipsia (excessive thirst)
• Nocturia (nighttime urination)
• Dilute urine (low osmolality, typically <200 mOsm/kg)
• Risk of dehydration and hypernatremia if fluid intake is inadequate

Diagnostic Approach

The diagnosis of diabetes insipidus involves:

1. Initial Laboratory Assessment:

   • Serum sodium and osmolality (typically elevated or high-normal)
   • Urine osmolality (inappropriately low, <200 mOsm/kg, despite elevated serum osmolality)
   • Urine volume measurement 1

2. Confirmatory Testing:

   • Water deprivation test with desmopressin challenge is the gold standard
   • Newer methods include hypertonic saline infusion with measurement of copeptin 1, 5

3. Differential Diagnosis: The following table outlines key diagnostic criteria:

   Condition	Urine Osmolality	Serum Sodium	Response to Desmopressin
   Central DI	<200 mOsm/kg	>145 mmol/L	Significant increase
   Nephrogenic DI	<200 mOsm/kg	>145 mmol/L	Minimal/no increase
   Primary Polydipsia	Variable, can exceed 300 mOsm/kg after water deprivation	Normal or low	Minimal increase
   Partial DI	250-750 mOsm/kg	Variable	Partial increase

4. Imaging:

   • MRI with and without IV contrast for suspected central DI to evaluate pituitary/hypothalamic region 1
   • Ultrasound of urinary tract for nephrogenic DI to detect complications

Management

Treatment depends on the type of diabetes insipidus:

Central Diabetes Insipidus

• First-line treatment: Desmopressin (synthetic vasopressin analog) 1, 6
  • Available as nasal spray, oral tablets, or injection
  • Nasal spray dosage: 0.1-0.4 mL daily in adults (10-40 mcg), either as single dose or divided into 2-3 doses
  • For children (3 months to 12 years): 0.05-0.3 mL daily
  • Approximately 25-33% of patients can be controlled with a single daily dose 6
  • Dose should be adjusted based on adequate sleep duration and appropriate water turnover

Nephrogenic Diabetes Insipidus

• First-line combination therapy: 1
  • Thiazide diuretic (hydrochlorothiazide 25 mg once or twice daily)
  • Amiloride if hypokalemia develops
  • Consider NSAIDs (prostaglandin synthesis inhibitors)
• Note: Desmopressin is ineffective and not indicated for nephrogenic DI 1, 6

General Management Principles

• Fluid management:

  • Ensure unrestricted access to water to prevent dehydration
  • Careful monitoring to prevent hyponatremia
  • Avoid hypotonic fluids (e.g., dextrose 5%) in central DI to prevent rapid hyponatremia 1

• Dietary modifications:

  • Low-salt diet (<6 g/day or 2.4 g sodium)
  • Low-protein diet (<1 g/kg/day) may be beneficial 1

Monitoring and Follow-up

Regular monitoring should include:

• Electrolytes (Na, K, Cl, HCO₃)
• Renal function (creatinine, eGFR)
• Uric acid levels
• Urine osmolality 1

For nephrogenic DI, imaging studies such as ultrasound of the urinary tract every 2-3 years are recommended to detect complications like hydronephrosis and bladder wall hypertrophy 1.

Complications to Monitor

• Hypernatremic dehydration (emergency in nephrogenic DI)
• Urological complications (reported in 46% of nephrogenic DI patients)
• Hydronephrosis and bladder dysfunction 1
• In adipsic DI, patients are at heightened risk for severe dehydration due to lack of thirst sensation 4

Special Considerations

• Elderly patients: Dose adjustment may be needed due to decreased renal function 6
• Genetic counseling: Recommended for familial forms of DI 1
• Nasal congestion: Alternative routes of desmopressin administration may be needed when nasal delivery is compromised 6
• Quality of life: Some patients with treated central DI may still experience reduced quality of life, possibly due to concurrent oxytocin deficiency 2