Likelihood of Undiagnosed Diabetes Insipidus with Normal ADH Levels
A normal ADH level (<0.8 reference range) does NOT rule out diabetes insipidus, and ADH measurement should not be used for diagnosis—the test has poor discriminatory value and conflicting data that make clinical interpretation unreliable. 1
Why ADH Levels Are Unreliable for DI Diagnosis
The American Association of Neurological Surgeons explicitly states that obtaining ADH levels is not supported by the literature (class III evidence), meaning this test should not guide clinical decision-making. 1
In prospective studies of patients with severe conditions, ADH was detectable in all patients regardless of whether they developed the expected clinical syndrome, demonstrating that the presence or absence of measurable ADH does not correlate with disease state. 1
The available data on ADH levels across various conditions are conflicting and inconsistent, making any attempt at clinical interpretation fundamentally unreliable. 1
The Correct Diagnostic Approach
Instead of ADH measurement, the diagnosis of DI requires simultaneous measurement of three parameters:
The pathognomonic finding for DI is urine osmolality <200 mOsm/kg H₂O combined with high-normal or elevated serum sodium. 2, 1 This triad confirms the diagnosis without needing ADH levels.
Distinguishing Central from Nephrogenic DI
Once DI is confirmed, plasma copeptin levels are the primary differentiating test to distinguish between central and nephrogenic diabetes insipidus—not ADH levels. 2, 1
- Copeptin >21.4 pmol/L indicates nephrogenic DI (kidney resistance to ADH) 2, 1
- Copeptin <21.4 pmol/L suggests central DI or primary polydipsia, requiring additional testing with hypertonic saline or arginine stimulation 2, 1
Alternatively, a desmopressin trial can differentiate between central and nephrogenic DI, with response to desmopressin indicating central DI and no response indicating nephrogenic DI. 2
Clinical Bottom Line
Do not order ADH levels thinking they will help diagnose or exclude diabetes insipidus—they will not provide clinically useful information and may lead to diagnostic confusion. 1
If you suspect DI based on clinical presentation (polyuria, polydipsia, inappropriately dilute urine), proceed directly to:
- Simultaneous measurement of serum sodium, serum osmolality, and urine osmolality 2, 1
- 24-hour urine volume measurement (>3 liters per 24 hours in adults confirms polyuria) 2
- Plasma copeptin measurement if initial biochemistry confirms DI 2, 1
- Water deprivation test followed by desmopressin administration remains the gold standard if copeptin is unavailable or results are equivocal 2, 3
The likelihood of having undiagnosed DI with a normal ADH level is impossible to determine because ADH levels do not correlate with DI presence or absence—you need the correct diagnostic tests listed above. 1