Could my normal serum sodium, serum osmolality, urine osmolality, copeptin and uric acid values be false‑negative for diabetes insipidus in the setting of polyuria (>3 L/day) and polydipsia?

Can Normal Lab Values Be False-Negative for Diabetes Insipidus?

Yes, your normal serum sodium, serum osmolality, urine osmolality, copeptin, and uric acid values can absolutely represent a "false-negative" pattern for diabetes insipidus—specifically, these results are consistent with partial central diabetes insipidus where you are compensating by drinking enough water to normalize your serum values. 1

Why Normal Values Don't Exclude Diabetes Insipidus

Normal serum sodium and osmolality do not exclude diabetes insipidus; they merely reflect that you are maintaining adequate fluid intake to offset urinary losses. 1 This is one of the most common diagnostic pitfalls in evaluating polyuria-polydipsia syndrome.

The Critical Misinterpretation

• Clinicians frequently misinterpret normal serum values as ruling out diabetes insipidus, overlooking that these values can be normal because the patient is compensating with increased water consumption 1
• Serum sodium alone is insufficient to assess hydration status in suspected diabetes insipidus, as patients can keep sodium within normal limits by drinking excessively 1
• The pathognomonic finding for diabetes insipidus is inappropriately dilute urine (urine osmolality <200 mOsm/kg) in combination with high-normal or elevated serum sodium—but this requires you to be somewhat dehydrated 2, 1

Understanding Partial Diabetes Insipidus

Your presentation is most consistent with partial central diabetes insipidus, which has distinct laboratory characteristics:

Diagnostic Pattern for Partial Central DI

• Urine osmolality between 250-750 mOsm/kg (rather than <100 mOsm/kg seen in severe complete DI) 1
• Normal serum sodium and osmolality when adequate free water access is maintained 1
• Stimulated copeptin <4.9 pmol/L strongly points to partial central diabetes insipidus rather than a true negative result 1
• Some residual ADH production remains, allowing urine osmolality in this intermediate range 1

Why Your Copeptin May Appear Normal

• Basal (unstimulated) copeptin measurements cannot reliably differentiate between primary polydipsia, partial central DI, and complete central DI 3, 4
• Stimulated copeptin levels (after osmotic or arginine stimulation) are required to differentiate partial central DI from primary polydipsia 5, 4
• Unstimulated basal copeptin >20 pmol/L identifies nephrogenic DI, but lower values require stimulation testing 5, 4

What You Need Next: Proper Diagnostic Testing

Since you have polyuria >3 L/day with normal baseline labs, you need provocative testing to unmask the diagnosis:

Recommended Diagnostic Approach

1. Hypertonic saline infusion test with stimulated copeptin measurement 4

   • This induces hypernatremia to provide osmotic stimulation
   • Stimulated copeptin <4.9 pmol/L confirms partial central DI 1
   • Superior to classical water deprivation test but requires close supervision 4

2. Alternative: Arginine stimulation test 4

   • Shorter and safer than hypertonic saline
   • Also measures stimulated copeptin levels 4

3. Genetic testing should be considered early 2

   • Approximately 90% of congenital cases are X-linked (AVPR2 gene) 2, 1
   • <10% are autosomal (AQP2 gene) 2, 1
   • Can avoid potentially harmful water deprivation testing 2

4. Pituitary MRI 6

   • Look for loss of posterior pituitary bright spot (marks absence of AVP) 6
   • Evaluate for structural lesions, especially if acquired DI 6

Critical Clinical Pitfalls to Avoid

• Do NOT rely on clinical signs like skin turgor, mouth dryness, or urine color to assess hydration status—these are unreliable 1
• Do NOT assume normal serum sodium rules out DI—this is the most common diagnostic error 1
• Do NOT perform water deprivation testing without measuring copeptin—indeterminate results occur frequently, and stimulated copeptin helps reclassify these patients 3
• In severe forms, urine osmolality remains <250 mOsm/kg with serum sodium >145 mmol/L, but partial forms have urine osmolality 250-750 mOsm/kg 6

Treatment Implications

Treatment with desmopressin (DDAVP) is necessary for partial central DI 1 to prevent chronic mild hypernatremia and its long-term complications, including seizures, developmental delay, and cognitive impairment 2, 1. Ensuring adequate free water access at all times is crucial 1.