What is the drug of choice for central diabetes insipidus (DI), characterized by polyuria and absence of the posterior pituitary bright spot on Magnetic Resonance Imaging (MRI), in a patient with severe dehydration?

Drug of Choice for Central Diabetes Insipidus

Desmopressin (Option A) is the drug of choice for central diabetes insipidus in this patient with post-traumatic polyuria, severe dehydration, and absent posterior pituitary bright spot on MRI. 1

Clinical Presentation Analysis

This patient presents with the classic triad of central diabetes insipidus (CDI):

• Polyuria following head trauma (1 month post-injury) 2
• Severe dehydration with impaired consciousness (from inability to maintain adequate fluid intake during hunger strike) 2
• Absent posterior pituitary bright spot on MRI (pathognomonic for CDI, indicating loss of neurosecretory granules) 3

The history of head trauma is a well-established cause of CDI, as traumatic brain injury can damage the hypothalamic-neurohypophyseal axis 4, 5.

Why Desmopressin is the Correct Answer

Desmopressin is FDA-approved and universally recognized as the treatment of choice for central diabetes insipidus. 1 The FDA label explicitly states: "Desmopressin Acetate Injection is indicated as antidiuretic replacement therapy in the management of central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region." 1

Mechanism and Efficacy

• Desmopressin is a synthetic vasopressin analog that directly replaces the deficient antidiuretic hormone (ADH/AVP) 1, 6
• It stimulates V2 receptors in the kidney, increasing water reabsorption and reducing urine output 1
• Clinical effects include reduced urinary output, increased urine osmolality, and decreased plasma osmolality 1
• It has selective antidiuretic activity with minimal vasopressor effects, making it safer than natural vasopressin 1, 6

Administration and Dosing

• Can be administered intravenously, subcutaneously, intranasally, or orally 1, 6
• Parenteral dosing: 2-4 mcg IV or subcutaneously 6
• Intranasal dosing: 10-40 mcg 6
• In this emergency setting with severe dehydration and impaired consciousness, IV administration is preferred 1

Why the Other Options are Incorrect

Thiazide Diuretics (Option C) and Amiloride/Triamterene (Options B & D)

These medications are used for nephrogenic diabetes insipidus (NDI), NOT central diabetes insipidus. 7

• The FDA label explicitly states: "Desmopressin Acetate Injection is ineffective and not indicated for the treatment of nephrogenic diabetes insipidus." 1
• Thiazides work by inducing mild volume depletion and enhancing proximal water reabsorption, which is a compensatory mechanism useful only when the kidney cannot respond to ADH 7
• In CDI, the kidneys are fully capable of responding to ADH—the problem is ADH deficiency, making diuretics both ineffective and potentially harmful 7
• Amiloride is specifically used in combination with thiazides for NDI, particularly in lithium-induced cases 7
• The distinguishing characteristic in the differential diagnosis table clearly states: Central DI responds to DDAVP (desmopressin), while NDI does not 7

Clinical Distinction: Central vs. Nephrogenic DI

This patient has central DI based on:

• Post-traumatic etiology (head injury affecting hypothalamus/pituitary) 2, 4
• Absent posterior pituitary bright spot on MRI (indicates loss of ADH-containing neurosecretory granules) 3
• If copeptin were measured, it would be low or absent in CDI (versus elevated >21.4 pmol/L in NDI) 7, 3

Immediate Management Priorities

Acute Stabilization

• Immediate IV fluid resuscitation with hypotonic fluids (5% dextrose in water, NOT normal saline) 7, 8
• Normal saline should be avoided because its tonicity (~300 mOsm/kg H₂O) exceeds typical urine osmolality in DI and can worsen hypernatremia 7
• Close monitoring of serum sodium, fluid balance, and neurological status 7
• Correction of hypernatremia should be gradual to avoid cerebral edema 7

Desmopressin Initiation

• Start desmopressin once diagnosis is confirmed and acute dehydration is being corrected 1
• Monitor for hyponatremia (main side effect of desmopressin treatment) 5, 9
• Adjust fluid intake appropriately once antidiuretic effect begins 2

Common Pitfalls to Avoid

• Do not use thiazide diuretics for central DI—this is a fundamental error that confuses CDI with NDI 7, 1
• Do not use normal saline for rehydration in hypernatremic DI patients—use hypotonic fluids like D5W 7, 8
• Do not correct hypernatremia too rapidly—risk of cerebral edema 7
• Do not withhold desmopressin while correcting dehydration—both should be addressed, but fluid resuscitation takes initial priority 2