Can my diabetes insipidus test be falsely negative despite a concentrated urine, normal serum sodium, normal serum osmolality and low copeptin?

Can Diabetes Insipidus Tests Be Falsely Negative?

Yes, your diabetes insipidus tests can be falsely negative—the combination of concentrated urine (>250 mOsm/kg), normal serum sodium, normal serum osmolality, and low copeptin (<4.9 pmol/L) strongly suggests partial central diabetes insipidus rather than a true negative result. 1, 2

Understanding Your Test Results

Your laboratory findings represent a diagnostic gray zone that requires careful interpretation:

• Urine osmolality between 250-750 mOsm/kg indicates partial diabetes insipidus, not normal kidney function 3
• In severe complete DI, urine osmolality would be <100-250 mOsm/kg, but partial forms present with intermediate values 4, 3
• Normal serum sodium and osmolality do NOT rule out diabetes insipidus—they simply indicate you are maintaining adequate fluid intake to compensate for urinary losses 1, 4

Why Low Copeptin Matters

The low copeptin level is actually the most revealing finding:

• Copeptin <4.9 pmol/L after osmotic stimulation (hypertonic saline test) confirms central diabetes insipidus with >94% accuracy 2, 5
• Low copeptin reflects inadequate vasopressin production, which is the hallmark of central DI 2, 6
• Basal (unstimulated) copeptin alone cannot differentiate between partial central DI and primary polydipsia—you need stimulated copeptin levels 5, 7

The Critical Diagnostic Pitfall

Your results illustrate a common diagnostic error:

• Clinicians often misinterpret "normal" serum values as excluding DI, when these values are only normal because the patient is drinking enough to compensate 1, 4
• The key question is: Can you concentrate your urine appropriately when osmotically challenged? 3, 2
• If your urine osmolality remains <750-800 mOsm/kg despite serum osmolality >295 mOsm/kg, this is pathognomonic for DI 4

Recommended Next Steps

To definitively diagnose or exclude partial central DI:

1. Undergo hypertonic saline infusion test with copeptin measurement 2, 5

   • This test induces hypernatremia to maximally stimulate vasopressin release
   • Stimulated copeptin <4.9 pmol/L confirms central DI with high diagnostic accuracy
   • This test is superior to the classical water deprivation test 2, 5

2. Alternative: Arginine stimulation test 2

   • Shorter and safer than hypertonic saline
   • Also measures stimulated copeptin levels
   • Provides similar diagnostic accuracy

3. Obtain pituitary MRI 3

   • Look for absence of posterior pituitary bright spot (indicates lack of vasopressin stores)
   • Evaluate for structural lesions of pituitary gland or stalk
   • Essential for identifying treatable causes

4. Consider genetic testing if congenital DI suspected 4

   • 90% of congenital cases are X-linked (AVPR2 gene)
   • <10% are autosomal recessive (AQP2 gene)

Clinical Management Implications

Even with "borderline" results, treatment may be warranted:

• Partial central DI with residual vasopressin production still requires desmopressin (DDAVP) therapy 4
• The goal is to prevent chronic mild hypernatremia and its long-term complications 1
• Ensure free water access at all times—this is crucial regardless of final diagnosis 4

Common Pitfalls to Avoid

• Do NOT rely on single unstimulated copeptin measurement to exclude central DI—stimulation testing is essential 5, 7
• Do NOT assume normal hydration based on serum sodium alone—patients with DI maintain normal sodium by drinking excessively 1, 4
• Do NOT use clinical signs (skin turgor, mouth dryness) to assess diagnosis—these are unreliable 4, 8
• Do NOT accept "indeterminate" water deprivation test results without further workup—copeptin measurement can reclassify these patients accurately 7