What are the diagnostic criteria for diabetes insipidus?

Diagnostic Criteria for Diabetes Insipidus

Diabetes insipidus is diagnosed when inappropriately dilute urine (osmolality <200 mOsm/kg H₂O) occurs in combination with high-normal or elevated serum sodium—this finding is pathognomonic for the disorder. 1, 2

Initial Biochemical Work-Up

The diagnostic approach begins with three essential measurements 1, 2:

• Serum sodium - typically high-normal or elevated 1, 2
• Serum osmolality - to assess systemic hydration status 1, 2
• Urine osmolality - the key finding is <200 mOsm/kg H₂O despite elevated serum sodium 1, 2

Measure plasma copeptin levels as a surrogate marker for arginine vasopressin (AVP), which helps differentiate between central and nephrogenic forms 3, 2, 4:

• Copeptin <21.4 pmol/L indicates central diabetes insipidus (AVP deficiency) 3, 2
• Copeptin >21.4 pmol/L suggests nephrogenic diabetes insipidus (AVP resistance) 2

Clinical Presentation to Recognize

Suspect diabetes insipidus in patients presenting with 1, 2:

• Polyuria (>2.5 L per 24 hours despite attempts to reduce fluid intake) 2
• Polydipsia with preference for cold water 1
• Hypernatremic dehydration 1, 2
• Failure to thrive (particularly in infants and children) 1, 2

Confirmatory Testing Algorithm

For Suspected Central Diabetes Insipidus (copeptin <21.4 pmol/L):

Perform one of the following confirmatory tests 3:

1. Hypertonic saline infusion test - stimulates copeptin release; failure to increase copeptin confirms central DI 3, 4
2. Arginine stimulation test - alternative nonosmotic stimulus that is better tolerated 3, 4

Important caveat: The hypertonic saline test requires sodium monitoring every 30 minutes to prevent dangerous hypernatremia 4

For Suspected Nephrogenic Diabetes Insipidus:

• Morning urine osmolality after overnight fluid avoidance - concentrations >600 mOsm/L rule out diabetes insipidus 2
• Genetic testing is strongly recommended, especially in children, testing at minimum AQP2, AVPR2, and AVP genes 1, 2
• Genetic testing can avoid potentially harmful water deprivation tests and provides definitive diagnosis 1, 2

Desmopressin Response Test

Administer desmopressin and monitor response 3:

• Central DI: Shows decreased urine output and increased urine osmolality (positive response) 3
• Nephrogenic DI: No response to desmopressin 3

This test definitively distinguishes central from nephrogenic forms 3

Critical Pitfalls to Avoid

The traditional water deprivation test has significant limitations including long duration (17 hours), poor diagnostic accuracy, and potential for dangerous dehydration—newer copeptin-based tests are superior 4, 5. However, genetic testing for nephrogenic DI can eliminate the need for these challenging procedures entirely 1, 2.

Do not use salt-containing IV solutions (0.9% NaCl) in suspected DI patients as their tonicity (300 mOsm/kg) exceeds typical DI urine osmolality (100 mOsm/kg) by 3-fold, risking severe hypernatremia 1. Use 5% dextrose instead 1.

Family History and Imaging

• Construct a detailed pedigree to identify X-linked nephrogenic DI (90% of hereditary cases affect males) or autosomal forms 1, 2
• MRI of the sella with and without contrast using high-resolution pituitary protocols is the preferred imaging for central DI to evaluate the hypothalamic-pituitary axis 1
• Look for absent T1 hyperintensity of the posterior pituitary (normally present from neurosecretory granules) 1