What is the recommended treatment for a 61-year-old female with suspected diabetes insipidus, presenting with hypernatremia, low antidiuretic hormone (ADH) levels, and impaired urine concentration?

Diagnosis and Treatment of Central Diabetes Insipidus

Definitive Diagnosis

This patient has central diabetes insipidus (CDI) based on the combination of inappropriately dilute urine (osmolality 220 mOsm/kg) in the setting of high-normal serum sodium (143 mEq/L) and serum osmolality (295 mOsm/kg), with undetectable ADH (<0.8 pg/mL). 1, 2

Key Diagnostic Features Supporting CDI:

• Urine osmolality of 220 mOsm/kg is pathologically dilute when serum osmolality is 295 mOsm/kg—normal kidneys should concentrate urine to >600 mOsm/kg in response to this degree of serum hyperosmolarity 3, 2
• Undetectable ADH (<0.8 pg/mL) with high-normal serum osmolality confirms inadequate ADH secretion, distinguishing this from nephrogenic DI where ADH would be elevated 1, 2
• The 24-hour urine volume of 1.3L is relatively low because this patient likely has intact thirst mechanism and is compensating by drinking to maintain near-normal sodium 1

Critical Pitfall to Avoid:

The relatively "normal" 24-hour urine volume (1.3L) does not rule out DI—many patients with DI maintain lower urine volumes through compensatory fluid intake driven by thirst 1. The diagnostic key is the inappropriately dilute urine relative to serum osmolality, not the absolute urine volume 2.

Immediate Management Steps

1. Confirm Diagnosis with Desmopressin Trial

Administer desmopressin 2-4 mcg subcutaneously or intravenously as a single test dose to confirm central DI—response with increased urine osmolality (>600 mOsm/kg) and decreased urine output confirms the diagnosis 1, 2, 4

2. Mandatory Imaging Workup

Order MRI of the sella with dedicated high-resolution pituitary sequences immediately 1, 2. This is non-negotiable because:

• Approximately 50% of central DI cases have identifiable structural causes including tumors, infiltrative diseases, or inflammatory processes 1
• DI at presentation strongly suggests craniopharyngioma, histiocytosis, or germ-cell tumor rather than pituitary adenoma 2
• Look for absence of the posterior pituitary "bright spot" on T1-weighted images, which is a critical diagnostic finding 2

3. Ensure Unrestricted Water Access

The patient must have free access to plain water 24/7—this is life-saving 1, 3. Never restrict fluids in DI patients, as this causes life-threatening hypernatremic dehydration 3. Allow the patient to drink to thirst rather than calculated requirements, as osmosensors triggering thirst are more sensitive and accurate than medical calculations 1, 3.

Definitive Treatment Protocol

Pharmacologic Management

Initiate desmopressin (DDAVP) as the treatment of choice for central DI 1, 4:

• Starting dose: 2-4 mcg daily subcutaneously or intravenously in one or two divided doses 1, 4
• Alternative routes include intranasal (10-40 mcg daily) or oral (0.1-0.2 mg twice daily) 5, 6
• Desmopressin reduces urinary output, increases urine osmolality, and decreases plasma osmolality through V2 receptor stimulation 4

Critical Monitoring Requirements

Check serum sodium within 7 days of starting desmopressin, then at 1 month, then every 2-3 months 1, 3. This is essential because:

• Hyponatremia is the main complication of desmopressin therapy and can be life-threatening 1, 5
• During initial treatment, monitor serum sodium every 2-3 days, then weekly until stable 3
• Measure 24-hour urine volume monthly initially to assess treatment effectiveness 3

Fluid Management During Treatment

Implement moderate fluid restriction during desmopressin therapy to prevent dilutional hyponatremia 2, 4. However, this must be balanced carefully:

• Never completely restrict water access 3
• Adjust fluid intake based on urine output and serum sodium levels 4
• If hyponatremia develops, reduce desmopressin dose or frequency rather than severely restricting fluids 4

Additional Workup Required

Endocrine Evaluation

• Check for other pituitary hormone deficiencies including TSH, free T4, cortisol, LH, FSH, prolactin, and IGF-1, as central DI often occurs with other pituitary pathology 1
• Consider testing for autoimmune markers if infiltrative disease is suspected 1

Renal Monitoring

• Perform renal ultrasound at baseline and every 2 years to monitor for urinary tract dilation from chronic polyuria 1, 3
• Monitor serum creatinine and electrolytes every 2-3 months initially 1

Common Pitfalls and How to Avoid Them

Pitfall 1: Misinterpreting "Normal" Urine Volume

Do not be falsely reassured by a 24-hour urine volume of only 1.3L—the diagnostic criterion is inappropriately dilute urine relative to serum osmolality, not absolute polyuria 1, 2. This patient is likely drinking enough to compensate.

Pitfall 2: Using Normal Saline for IV Rehydration

If IV fluids are needed, use 5% dextrose in water (D5W), NOT normal saline 3. Normal saline will worsen hypernatremia in DI patients 3.

Pitfall 3: Delaying Imaging

Never delay MRI imaging while waiting for treatment response—structural lesions causing DI require urgent identification and may need neurosurgical intervention 1, 2.

Pitfall 4: Over-treating with Desmopressin

Start with low doses and titrate slowly 4. Excessive desmopressin causes dangerous hyponatremia, which can lead to seizures, cerebral edema, and death 1, 4, 5.

Long-term Management Considerations

• Annual clinical follow-up with weight measurements and complete metabolic panel including sodium, potassium, chloride, bicarbonate, creatinine, and uric acid 1
• Annual urinalysis including osmolality and 24-hour urine volume 1
• Patients with DI have approximately 50% risk of developing CKD stage ≥2 and require monitoring per KDIGO guidelines 1
• Provide emergency plan letter explaining diagnosis and IV fluid management (D5W at maintenance rate) for emergency situations 3