What labs are used to diagnose diabetes insipidus?

Laboratory Tests for Diagnosing Diabetes Insipidus

The initial laboratory workup for suspected diabetes insipidus requires simultaneous measurement of serum sodium, serum osmolality, and urine osmolality—this triad confirms the diagnosis when urine osmolality is <200 mOsm/kg with high-normal or elevated serum sodium. 1, 2

Initial Biochemical Screening

The diagnostic approach begins with these essential baseline tests:

• Serum sodium: Look for high-normal or elevated levels (>145 mmol/L indicates hypernatremia) 1, 2
• Serum osmolality: Typically elevated or high-normal in diabetes insipidus 1, 2, 3
• Urine osmolality: The hallmark finding is inappropriately dilute urine (<200 mOsm/kg) despite serum hyperosmolality 1, 2, 4
• 24-hour urine volume: Polyuria is defined as >3 liters per 24 hours in adults or >2.5 L/day 2, 4

A critical pitfall: First check blood glucose to exclude diabetes mellitus, as elevated glucose (≥126 mg/dL fasting or ≥200 mg/dL random with symptoms) indicates diabetes mellitus, not diabetes insipidus—these are completely different diseases despite similar names. 2

Differentiating Central from Nephrogenic Diabetes Insipidus

Once diabetes insipidus is confirmed, the next step distinguishes between central (vasopressin deficiency) and nephrogenic (vasopressin resistance) forms:

Plasma Copeptin Measurement (Preferred Modern Approach)

Plasma copeptin is now the primary differentiating test and has largely replaced direct AVP measurement due to superior stability and ease of measurement. 1, 2, 5

• Baseline copeptin >21.4 pmol/L: Diagnostic for nephrogenic diabetes insipidus with high precision 1, 2
• Baseline copeptin <21.4 pmol/L: Indicates either central diabetes insipidus or primary polydipsia, requiring additional stimulation testing 1, 2

For patients with copeptin <21.4 pmol/L, stimulation testing is needed:

• Hypertonic saline infusion test: Copeptin levels after osmotic stimulation differentiate central DI from primary polydipsia with superior accuracy compared to water deprivation 1, 5
• Arginine stimulation test: A newer, better-tolerated alternative that stimulates copeptin release 5

Water Deprivation Test (Traditional but Limited)

The water deprivation test, while historically considered the "gold standard," has significant limitations including limited diagnostic accuracy, long duration (up to 17 hours), and risk of severe hypernatremic dehydration. 1, 6, 4, 5

Critical contraindications for water deprivation testing 6:

• Confirmed nephrogenic diabetes insipidus (especially in infants and children)
• Pre-existing hypernatremia (Na >145 mmol/L)
• Clinical evidence of dehydration
• Advanced chronic kidney disease (stage ≥G4)

The test protocol involves:

• Measuring urine osmolality after fluid deprivation 4, 3, 7
• Administering desmopressin and remeasuring urine osmolality 4, 7
• Response to desmopressin (increased urine concentration) indicates central DI 2, 7
• No response to desmopressin indicates nephrogenic DI 2, 7

Genetic Testing

For confirmed or suspected nephrogenic diabetes insipidus, genetic testing with a multigene panel including AVPR2, AQP2, and AVP genes is strongly recommended, even in adults and females. 1, 2

Key points about genetic testing:

• Should be performed in accredited diagnostic laboratories 1
• Includes copy number variant analysis 1
• Identifies pathogenic variants in 90-95% of cases 1
• Essential for family planning, genetic counseling, and presymptomatic testing of at-risk family members 1
• In male offspring of AVPR2 mutation carriers, testing umbilical cord blood immediately after birth prevents primary manifestations through early treatment 1

Additional Supporting Laboratory Tests

Baseline Metabolic Panel

• Serum electrolytes: Sodium, potassium, chloride, bicarbonate 2
• Serum creatinine and uric acid: Assess kidney function and monitor for complications 2
• Urine specific gravity: Markedly decreased in diabetes insipidus 7

Monitoring Tests After Diagnosis

• Serum sodium within 7 days and at 1 month after starting treatment, then periodically—hyponatremia is the main complication of desmopressin therapy 2
• Routine measurements every 2-3 months for infants, annually for adults 2
• Renal ultrasound at least every 2 years to monitor for urinary tract dilation from chronic polyuria 2

Imaging Studies

MRI with dedicated pituitary/sella sequences is essential when central diabetes insipidus is suspected, as it identifies structural causes including tumors, infiltrative diseases, and post-surgical changes. 2

Common Diagnostic Pitfalls

1. Confusing diabetes insipidus with diabetes mellitus: Always check glucose first—diabetes mellitus causes polyuria through osmotic diuresis from glucosuria with HIGH urine osmolality, whereas diabetes insipidus has LOW urine osmolality 2

2. Misinterpreting borderline urine osmolality (200-300 mOsm/kg): Many conditions cause this range without representing true diabetes insipidus, including partial dehydration or chronic kidney disease 2

3. Restricting water access during evaluation: This is life-threatening—patients must have free access to fluids at all times to prevent severe hypernatremic dehydration 2

4. Using water deprivation test in confirmed nephrogenic DI: This is contraindicated and dangerous, particularly in children 6