What are the diagnostic criteria for diabetes insipidus based on plasma and urine osmolality?

Diagnosis of Diabetes Insipidus Based on Plasma and Urine Osmolality

The diagnosis of diabetes insipidus is established when plasma osmolality is >300 mOsm/kg with inappropriately low urine osmolality (<300 mOsm/kg), indicating failure of urinary concentration despite adequate physiologic stimulus. 1, 2

Diagnostic Criteria

Key Laboratory Parameters

• Plasma/Serum Osmolality: >300 mOsm/kg indicates dehydration and is a threshold for diabetes insipidus diagnosis 3
• Urine Osmolality: Inappropriately low (<300 mOsm/kg) in the setting of elevated plasma osmolality 1
• Urine-to-Plasma Osmolality Ratio: A low ratio confirms impaired concentrating ability 2

Diagnostic Algorithm

1. Initial Assessment:

   • Measure serum sodium, plasma osmolality, and urine osmolality simultaneously 2
   • Plasma osmolality >300 mOsm/kg with urine osmolality <300 mOsm/kg is pathognomonic for diabetes insipidus 1

2. If Initial Results Are Equivocal:

   • Perform water deprivation test with vasopressin challenge 4
   • A simplified approach shows that after 12 hours of fasting, the combination of urine osmolality <400 mOsm/kg and serum osmolality >302 mOsm/kg has 90% sensitivity and 98% specificity for diabetes insipidus 5

3. Differential Diagnosis:

   • Central DI: Responds to vasopressin with increased urine osmolality 6
   • Nephrogenic DI: No significant response to vasopressin 6
   • Primary Polydipsia: Normal or high urine osmolality after water deprivation 4

Types of Diabetes Insipidus and Their Diagnostic Features

Central Diabetes Insipidus

• Deficient AVP production from the posterior pituitary 4
• Diagnostic features:
  • Low urine osmolality (<300 mOsm/kg) with high plasma osmolality (>300 mOsm/kg) 1
  • Significant increase in urine osmolality (>50% or >300 mOsm/kg) after vasopressin administration 6
  • Absence of hyperintensity signal in posterior pituitary on MRI 4

Nephrogenic Diabetes Insipidus

• Resistance to AVP action at the kidney level 1
• Diagnostic features:
  • Low urine osmolality (<500 mOsm/kg) despite elevated plasma osmolality 1
  • Minimal or no increase in urine osmolality after vasopressin administration 6
  • Baseline plasma copeptin >21.4 pmol/L is diagnostic in adults 1

Water Deprivation Test Protocol

1. Preparation:

   • Baseline measurements of body weight, serum sodium, plasma osmolality, and urine osmolality 5
   • Test should begin in the morning after overnight fasting 5

2. During Test:

   • Withhold all fluids
   • Monitor weight, vital signs, serum sodium, and osmolality hourly 5
   • Terminate test if:
     • Weight decreases >3%
     • Plasma osmolality exceeds 300 mOsm/kg
     • Serum sodium exceeds 145 mmol/L 4

3. Interpretation:

   • Central DI: Urine osmolality remains <300 mOsm/kg during water deprivation but increases >50% after vasopressin 4
   • Nephrogenic DI: Urine osmolality remains <300 mOsm/kg and shows minimal response to vasopressin (<10% increase) 4
   • Primary Polydipsia: Urine osmolality typically increases to >750 mOsm/kg during water deprivation 4

Important Considerations

• In partial forms of diabetes insipidus (urine osmolality between 250-750 mOsm/kg), water deprivation test is valuable to demonstrate the inability to maximally concentrate urine 4
• Interpretation of raised serum osmolality depends on checking that serum glucose and urea are within normal range 3
• When directly measured osmolality is unavailable, the osmolarity equation can be used: osmolarity = 1.86 (Na+ + K+) + 1.15 glucose + urea + 14 (all in mmol/L), with an action threshold of >295 mmol/L 3
• Simple signs like skin turgor, mouth dryness, urine color, or specific gravity should NOT be used to assess hydration status, especially in older adults 3

Pitfalls to Avoid

• Failing to exclude other causes of polyuria (e.g., diabetes mellitus, hypercalcemia) before diagnosing diabetes insipidus 4
• Misinterpreting partial forms of diabetes insipidus, which may show intermediate responses 4
• Overlooking the risk of severe dehydration during water deprivation testing 5
• Not considering that medications (lithium, demeclocycline) can cause nephrogenic diabetes insipidus 6