What is the diagnosis and treatment for a patient with a low Antidiuretic Hormone (ADH) level of <0.8, with a reference range of 0.0-4.7, suggestive of diabetes insipidus?

Diagnosis of Diabetes Insipidus with ADH <0.8

An ADH level of <0.8 pg/mL in the context of hypotonic polyuria, hypernatremia, and inappropriately dilute urine strongly suggests central diabetes insipidus (DI), but the diagnosis requires confirmation with clinical context and functional testing rather than relying on ADH measurement alone.

Understanding ADH Measurement Limitations

ADH (vasopressin) levels are notoriously difficult to interpret in isolation because:

• ADH assays are technically challenging with significant variability between laboratories, and the hormone is unstable requiring immediate processing 1, 2
• Normal ADH ranges vary widely depending on plasma osmolality and volume status, making a single value difficult to interpret 3
• The diagnosis of DI is fundamentally clinical, based on the triad of hypotonic polyuria (>3L/day in adults), inappropriately dilute urine (osmolality <300 mOsm/kg), and elevated or high-normal plasma osmolality 1, 2

Diagnostic Approach to Suspected DI

Initial Clinical Assessment

Look for these specific features:

• Polyuria volume: >3 L/day in adults or >2 mL/kg/hr in children 3
• Urine osmolality: <300 mOsm/kg despite plasma hyperosmolality 1
• Plasma sodium and osmolality: Elevated (Na >145 mEq/L, osmolality >295 mOsm/kg) if patient cannot access water freely 1, 3
• Extreme thirst and preference for cold water is characteristic 3
• Nocturia causing significant sleep disruption 4

Gold Standard Diagnostic Testing

The water deprivation test followed by desmopressin administration remains the gold standard for distinguishing central DI from nephrogenic DI and primary polydipsia 1, 2:

1. Water deprivation phase: Withhold fluids until plasma osmolality >295 mOsm/kg or urine osmolality plateaus 1
2. Measure paired plasma and urine osmolality every 1-2 hours 1
3. Administer desmopressin (2-4 mcg subcutaneous or IV) after adequate dehydration 5, 1
4. Measure urine osmolality response 2-4 hours post-desmopressin 1

Interpretation:

• Central DI: Urine osmolality remains <300 mOsm/kg during dehydration but increases >50% after desmopressin 1, 2
• Nephrogenic DI: Urine osmolality remains <300 mOsm/kg both during dehydration and after desmopressin 1, 2
• Primary polydipsia: Urine osmolality concentrates appropriately (>600 mOsm/kg) during dehydration 1

Emerging Diagnostic Tool: Copeptin

Copeptin measurement during hypertonic saline stimulation is emerging as a more reliable alternative to direct ADH measurement 1, 6:

• Copeptin is a stable surrogate marker of ADH secretion 1, 6
• Copeptin <4.9 pmol/L after hypertonic saline infusion suggests central DI 6
• This test may simplify and improve diagnostic accuracy compared to water deprivation 1, 6

Treatment Once Central DI is Confirmed

First-Line Treatment: Desmopressin (DDAVP)

Desmopressin is the definitive treatment for central DI 5, 4, 7, 3:

Dosing options 5, 7:

• Subcutaneous/IV: Start 2-4 mcg daily in 1-2 divided doses for treatment-naïve patients 5
• Intranasal spray: 10-40 mcg daily in 1-2 divided doses 4, 7
• Sublingual lyophilisate: Better bioavailability than tablets, dose-titrated by patient 7

Key management principles:

• Patients self-titrate to the minimal effective dose that prevents excessive polyuria, particularly at night 7
• Fluid restriction during treatment is essential to prevent hyponatremia 5, 7
• Monitor serum sodium within 7 days, at 1 month, then periodically—more frequently in elderly patients 5
• Patient education is critical to avoid water intoxication and hyponatremia 7

When Intranasal Route is Compromised

Use subcutaneous or IV desmopressin in these situations 5, 4:

• Nasal congestion, blockage, or discharge 4
• Atrophic rhinitis or nasal mucosa atrophy 4
• Impaired consciousness 4
• Post-transsphenoidal surgery or nasal packing 4

Critical Safety Considerations

Hyponatremia Risk

Desmopressin can cause life-threatening hyponatremia leading to seizures, coma, respiratory arrest, or death 5:

• Ensure serum sodium is normal before starting or resuming desmopressin 5
• Contraindicated in patients with: excessive fluid intake, illnesses causing fluid/electrolyte imbalances, loop diuretic use, or glucocorticoid therapy 5
• Implement fluid restriction during treatment 5, 7
• If hyponatremia develops, temporarily or permanently discontinue desmopressin 5

Distinguishing Central from Nephrogenic DI

This distinction is essential because treatment differs fundamentally 2:

• Central DI: Responds to desmopressin 5, 1, 3
• Nephrogenic DI: Does not respond to desmopressin; requires discontinuation of offending medications, renal-friendly diet, and paradoxically, thiazide diuretics 3
• Desmopressin is ineffective and not indicated for nephrogenic DI 5, 4

Common Pitfalls to Avoid

• Do not rely on a single ADH measurement to diagnose DI—functional testing is required 1, 2
• Do not confuse DI with diabetes mellitus—recent nomenclature proposes "vasopressin deficiency" for central DI to avoid this confusion 6
• Do not overlook primary polydipsia in the differential, which requires behavioral therapy rather than desmopressin 3, 6
• Do not forget to assess for transient DI following head trauma or pituitary surgery, which may resolve spontaneously 5, 4
• Do not use desmopressin without ensuring adequate patient education about fluid restriction to prevent hyponatremia 7