Does a urine osmolality of 220 indicate diabetes insipidus?

A Urine Osmolality of 220 mOsm/kg Does NOT Definitively Indicate Diabetes Insipidus

A random urine osmolality of 220 mOsm/kg is inappropriately dilute and raises suspicion for diabetes insipidus, but the diagnosis cannot be made without simultaneously measuring serum/plasma osmolality and serum sodium. The diagnosis of diabetes insipidus requires the combination of plasma osmolality >300 mOsm/kg with urine osmolality <300 mOsm/kg—demonstrating failure of urinary concentration despite adequate physiologic stimulus 1.

Why Urine Osmolality Alone Is Insufficient

• Diabetes insipidus is defined by the combination of elevated plasma osmolality (>300 mOsm/kg) with inappropriately low urine osmolality (<300 mOsm/kg) 1
• Your urine osmolality of 220 mOsm/kg is indeed dilute, but without knowing the simultaneous plasma osmolality, this could represent:
  • Diabetes insipidus (if plasma osmolality >300 mOsm/kg) 1
  • Primary polydipsia (excessive water drinking causing dilute urine with low plasma osmolality) 2
  • Normal physiological response to high fluid intake 2

Required Diagnostic Workup

Measure these tests simultaneously to establish the diagnosis 1, 3:

• Serum/plasma osmolality (threshold: >300 mOsm/kg indicates dehydration and diabetes insipidus) 1
• Serum sodium (high-normal or elevated supports diabetes insipidus) 3
• Urine osmolality (you already have this: 220 mOsm/kg)
• 24-hour urine volume (>3 liters/day in adults or >4 mL/kg/hr in children confirms polyuria) 3, 4

The combination of plasma osmolality >300 mOsm/kg with urine osmolality <300 mOsm/kg is pathognomonic for diabetes insipidus 1, 5.

Distinguishing Between Types of Diabetes Insipidus

If diabetes insipidus is confirmed, plasma copeptin measurement is the primary test to differentiate central from nephrogenic diabetes insipidus 3:

• Copeptin >21.4 pmol/L = Nephrogenic diabetes insipidus 1, 3
• Copeptin <21.4 pmol/L = Central diabetes insipidus or primary polydipsia (requires further testing) 3

Alternatively, a desmopressin trial can differentiate the types: response to desmopressin indicates central diabetes insipidus, while no response indicates nephrogenic diabetes insipidus 3.

Critical Pitfalls to Avoid

• Never diagnose diabetes insipidus based on urine osmolality alone—serum osmolality must be simultaneously elevated 1
• Do not confuse diabetes insipidus with diabetes mellitus: diabetes mellitus causes polyuria through osmotic diuresis from glucosuria (with high urine osmolality from glucose), not from ADH deficiency 3, 6
• Check serum glucose first to exclude diabetes mellitus as the cause of polyuria 3
• Ensure serum glucose and urea are within normal range when interpreting elevated serum osmolality, as these can falsely elevate osmolality without true dehydration 7
• Simple signs like urine color, specific gravity, skin turgor, or mouth dryness should NOT be used to assess hydration status or diagnose diabetes insipidus 7, 1

Additional Considerations

• If plasma osmolality is unavailable, use the osmolarity equation: osmolarity = 1.86 (Na+ + K+) + 1.15 glucose + urea + 14 (all in mmol/L), with threshold >295 mmol/L 7, 1
• Ensure proper 24-hour urine collection by emptying the bladder at the start (discard this), then collecting all subsequent urine for exactly 24 hours, maintaining usual fluid intake based on thirst 3
• If diabetes insipidus is confirmed, obtain pituitary MRI with dedicated sella sequences to evaluate for central causes (tumors, infiltrative disease) 3
• Genetic testing with multigene panel (AVPR2, AQP2, AVP genes) is recommended if nephrogenic diabetes insipidus is confirmed 3