What test is used to diagnose diabetes insipidus?

Diagnostic Testing for Diabetes Insipidus

The initial diagnostic approach for diabetes insipidus involves measuring serum sodium, serum osmolality, and urine osmolality, with inappropriately diluted urine (osmolality <200 mOsm/kg H₂O) combined with high-normal or elevated serum sodium being pathognomonic for diabetes insipidus. 1

Initial Biochemical Work-Up

Measure these baseline values in all patients with suspected diabetes insipidus: 1

• Serum sodium (typically high-normal or elevated >145 mmol/L in severe cases) 1, 2
• Serum osmolality (elevated) 1, 3
• Urine osmolality (inappropriately low, typically <200 mOsm/kg H₂O in severe forms; 250-750 mOsm/kg H₂O in partial forms) 1, 2
• 24-hour urine volume (polyuria >3 liters/24 hours in adults) 2
• Plasma copeptin levels (surrogate marker for AVP; <21.4 pmol/l suggests central DI) 3, 4

The detection of inappropriately diluted urine with elevated serum sodium is pathognomonic and warrants early genetic testing if nephrogenic DI is suspected. 1

Confirmatory Testing

Water Deprivation Test

The water deprivation test remains the gold standard for differentiating central DI, nephrogenic DI, and primary polydipsia. 5, 6

Key protocol elements: 4, 2

• Discontinue diuretics and prostaglandin inhibitors at least 24 hours before testing 4
• Maintain normal sodium diet (≤6 g/day) for several days prior 4
• Monitor urine osmolality during water restriction 2, 7
• Urine osmolality >680-800 mOsm/kg after water deprivation rules out DI with 96-100% sensitivity and specificity 7

After water deprivation, administer desmopressin (DDAVP) and collect urine samples at 30,60, and 120 minutes: 4

• Central DI: Urine osmolality increases significantly after desmopressin 3, 8
• Nephrogenic DI: No response to desmopressin 3, 8
• Primary polydipsia: Urine already concentrated after water deprivation 7, 6

Copeptin-Based Testing (Emerging Alternative)

Plasma copeptin measurement with hypertonic saline infusion or arginine stimulation may simplify diagnosis and avoid the water deprivation test: 3, 4, 5

• Copeptin <2.5 pmol/l with plasma osmolality >290 mOsm/kg indicates central DI 7
• Copeptin >21.4 pmol/l effectively excludes central DI 3, 4

This approach is particularly valuable as it can avoid the "unpleasant, challenging, and potentially harmful" water deprivation test. 1

Genetic Testing

Early genetic testing is strongly recommended in suspected nephrogenic DI, particularly in infants and children presenting with polyuria, polydipsia, failure to thrive, and hypernatremic dehydration. 1

Genetic testing should be performed: 1

• In all symptomatic females (to identify X-linked carriers and autosomal forms) 1
• Using umbilical cord blood in male offspring of known AVPR2 mutation carriers 1
• In laboratories accredited for diagnostic genetic testing 1

Genetic testing can provide definitive diagnosis and avoid potentially harmful diagnostic procedures, preventing prolonged periods of severe hypertonic dehydration that can result in seizures, developmental delay, and cognitive impairment. 1

Critical Pitfalls to Avoid

Do not confuse diabetes insipidus with diabetes mellitus: 4, 2

• Always check blood glucose and rule out hyperglycemia/glucosuria before proceeding with DI testing 4

Plasma AVP measurement is unreliable: 7

• AVP levels do not reliably differentiate between central DI, nephrogenic DI, and primary polydipsia 7
• Use copeptin instead as a more stable surrogate marker 3, 7

The water deprivation test can be dangerous: 1

• Risk of severe dehydration, particularly in infants and young children 1
• Consider IV 5% dextrose in water at maintenance rate if fasting >4 hours 4
• Early genetic testing can avoid this test entirely in suspected nephrogenic DI 1