What is diabetic insipidus?

Diabetes Insipidus: Definition, Types, and Management

Diabetes insipidus (DI) is a disorder characterized by excessive urination (polyuria) and increased thirst (polydipsia) due to either deficient production of antidiuretic hormone (ADH) or kidney resistance to ADH action, resulting in the inability to concentrate urine. 1, 2

Types of Diabetes Insipidus

Central Diabetes Insipidus (CDI)

• Caused by deficient production or secretion of ADH (vasopressin) from the posterior pituitary gland 1, 3
• Characterized by low or absent plasma ADH levels despite increased plasma osmolality 1, 2
• Responds positively to desmopressin administration 1, 4
• May be idiopathic or secondary to head trauma, surgery, tumors, or infiltrative diseases affecting the hypothalamic-pituitary region 2, 5

Nephrogenic Diabetes Insipidus (NDI)

• Caused by kidney insensitivity to ADH despite normal or elevated plasma ADH levels 1, 6
• Can be congenital (genetic mutations in AVPR2 or AQP2 genes) or acquired (medications like lithium, electrolyte disorders) 6, 7
• Shows minimal or no response to desmopressin administration 1, 4
• Characterized by plasma copeptin levels above 21.4 pmol/l in adults 6, 7

Less Common Types

• Dipsogenic DI: Excessive water intake due to abnormal thirst mechanism 5
• Gestational DI: Occurs during pregnancy due to increased placental vasopressinase 5

Diagnostic Features

Clinical Presentation

• Polyuria (excessive urination, often 3-20 L/day) 2, 3
• Polydipsia (excessive thirst, preference for cold water) 2, 5
• Nocturia (nighttime urination) 2, 5
• Risk of dehydration and hypernatremia if fluid intake is restricted 7, 2

Laboratory Findings

• Decreased urine osmolality (<200 mOsm/kg H₂O) 7, 3
• Increased serum sodium and osmolality 7, 2
• Plasma copeptin levels help distinguish between types:

  • 21.4 pmol/l suggests nephrogenic DI 6, 7

  • <21.4 pmol/l suggests central DI or primary polydipsia 6, 7

Diagnostic Tests

• Water deprivation test followed by desmopressin administration is the gold standard 2, 3
• Response to desmopressin distinguishes central from nephrogenic DI 1, 3
• Genetic testing is recommended for suspected congenital NDI 7, 6

Management Approaches

Central Diabetes Insipidus

• Desmopressin (synthetic ADH analog) administration is the primary treatment 4, 2
• WARNING: Desmopressin can cause hyponatremia, which may be life-threatening if severe 4
• Contraindicated in patients with excessive fluid intake, conditions causing fluid/electrolyte imbalances, and those using loop diuretics or glucocorticoids 4
• Serum sodium should be monitored within 1 week and approximately 1 month after starting therapy 4

Nephrogenic Diabetes Insipidus

• Free access to water is essential in all patients with NDI to prevent dehydration, hypernatremia, growth failure, and constipation 7, 6
• Dietary modifications:
  • Low salt (≤6 g/day) and protein diet (<1 g/kg/day) to reduce renal osmotic load 6, 7
  • For infants: normal-for-age milk intake rather than water to ensure adequate calories 6, 7
• Pharmacological treatment:
  • Thiazide diuretics can reduce urine output by up to 50% when combined with a low-salt diet 6, 7
  • Amiloride may be added if hypokalemia develops 6, 7
  • Prostaglandin synthesis inhibitors (NSAIDs) may be beneficial but carry risks of gastrointestinal side effects 6, 7

Emergency Management

• Intravenous rehydration with 5% dextrose in water at maintenance rate for patients requiring fasting or experiencing dehydration 6, 7
• Avoid isotonic saline (0.9% NaCl) as it increases renal osmotic load and can worsen hypernatremia 6, 7
• Close monitoring of weight, fluid balance, and electrolytes during acute management 6, 7

Monitoring and Follow-up

Regular Assessment

• Height and weight monitoring, especially in children 7, 6
• Basic plasma biochemistry (Na, K, Cl, HCO₃, creatinine, osmolality) 7, 6
• Urine osmolality to assess treatment efficacy 7, 6
• Kidney ultrasound every 2 years to monitor for urinary tract dilatation 6, 7

Special Considerations

• Patients should have an emergency plan and wear medical alert identification 6, 7
• More frequent monitoring of serum sodium in patients over 65 years and those at increased risk of hyponatremia 4, 7
• Tube feeding may be considered for infants with repeated vomiting, dehydration, or failure to thrive 6, 7

Common Pitfalls and Caveats

• Do not confuse diabetes insipidus with diabetes mellitus - they are entirely different disorders with similar names 6, 8
• Desmopressin is ineffective and not indicated for nephrogenic diabetes insipidus 4, 1
• Salt-containing solutions should be avoided in acute management of DI as they increase renal osmotic load 6, 7
• Monitoring for hyponatremia is critical when using desmopressin, especially in elderly patients 4, 7
• Untreated DI can lead to chronic dehydration, growth failure in children, and neurological complications 6, 7