What is the test for Diabetic Insipidus (DI)?

Diagnostic Tests for Diabetes Insipidus

The primary diagnostic tests for diabetes insipidus (DI) include measurement of serum sodium, serum osmolality, urine osmolality, plasma copeptin levels, and specialized stimulation tests, with genetic testing strongly recommended for suspected nephrogenic diabetes insipidus. 1

Initial Diagnostic Approach

• Suspect diabetes insipidus in patients presenting with polyuria, polydipsia, and inappropriately dilute urine (urine osmolality <200 mOsm/kg H₂O) with high-normal or elevated serum sodium 1
• Initial biochemical work-up should include measurement of serum sodium, serum osmolality, and urine osmolality 2
• Inappropriately diluted urine (urinary osmolality <200 mOsm/kg H₂O) combined with high-normal or elevated serum sodium is pathognomonic for diabetes insipidus 2

Plasma Copeptin Testing

• Plasma copeptin measurement is recommended as a suitable alternative to AVP testing, as copeptin is released in equimolar ratio with AVP but is more stable and easier to measure 2
• Baseline plasma copeptin levels >21.4 pmol/l are diagnostic for nephrogenic diabetes insipidus in adults 2
• Adults with plasma copeptin <21.4 pmol/l should undergo further testing for central DI and primary polydipsia 2
• During hypertonic saline stimulation, a copeptin level of 4.9 pmol/l differentiates between central DI and primary polydipsia with high diagnostic accuracy 3

Specialized Stimulation Tests

• For patients with inconclusive initial results, specialized stimulation tests are required 1:

  • Water deprivation test followed by desmopressin administration (traditional gold standard) 4, 5
  • Hypertonic saline infusion test with copeptin measurement 3
  • Arginine stimulation test with copeptin measurement (better tolerated alternative) 3

• During water deprivation testing, urine osmolality >680 mOsm/kg after water deprivation has 100% sensitivity for diagnosing primary polydipsia versus diabetes insipidus 5

Genetic Testing

• Genetic testing is strongly recommended for suspected nephrogenic diabetes insipidus to provide an early and definitive diagnosis 2
• A massively parallel sequencing-based multigene panel that includes at least AQP2, AVPR2, and AVP genes is recommended 2
• Genetic testing can avoid unpleasant, challenging, and potentially harmful diagnostic procedures, including the desmopressin test or water deprivation test 2
• In families with known NDI, genetic testing in umbilical cord blood directly after birth is strongly recommended for male offspring of heterozygote AVPR2 mutation carriers 2

Differential Diagnosis

• Central DI (AVP deficiency): Responds to desmopressin administration 2, 6
• Nephrogenic DI: No response to desmopressin, high plasma copeptin levels 2
• Primary polydipsia: Responds to water deprivation with increased urine concentration 2
• Poorly controlled diabetes mellitus: High urine osmolality, hyperglycemia, glucosuria 2

Important Considerations and Pitfalls

• Desmopressin is ineffective for nephrogenic diabetes insipidus, making accurate diagnosis crucial before initiating treatment 6
• AVP levels alone do not reliably differentiate between central DI, nephrogenic DI, or primary polydipsia 5
• Nasal congestion, blockage, discharge, or atrophic rhinitis may compromise intranasal desmopressin administration, requiring alternative routes 6
• Partial forms of DI can be particularly challenging to diagnose, as laboratory test results may be difficult to interpret 2
• Regular monitoring of treatment efficacy via urine osmolality, urine output, weight gain, and growth is essential 1

Algorithm for Diagnosis

1. Initial evaluation: Measure serum sodium, serum osmolality, and urine osmolality 2
2. If urine osmolality <200 mOsm/kg with high-normal or elevated serum sodium, proceed to plasma copeptin measurement 2
3. If copeptin >21.4 pmol/l: Diagnosis of nephrogenic DI 2
4. If copeptin <21.4 pmol/l: Proceed to stimulation testing (hypertonic saline or arginine) 2, 3
5. For suspected nephrogenic DI: Perform genetic testing for AVPR2 and AQP2 mutations 2
6. For inconclusive cases: Perform water deprivation test followed by desmopressin administration 4, 5