Diabetes Insipidus (DI)

Diabetes insipidus is a disorder characterized by the inability of the kidneys to concentrate urine, resulting in excessive urine output (polyuria) and increased thirst (polydipsia). Unlike diabetes mellitus, DI is unrelated to blood glucose abnormalities but instead involves issues with antidiuretic hormone (ADH), also known as vasopressin, which regulates water balance in the body.

Types of Diabetes Insipidus

Central Diabetes Insipidus (CDI)

• Pathophysiology: CDI results from a deficiency of ADH due to damage to the hypothalamus or pituitary gland. This may occur secondary to head trauma, neurosurgery, infections (e.g., meningitis), tumors, or autoimmune disorders.
• Symptoms: Marked polyuria (usually >3 liters/day), polydipsia, nocturia, and dehydration if fluid intake is inadequate.
• Diagnosis: Low urine osmolality (<300 mOsm/kg) despite hypernatremia or elevated plasma osmolality. A water deprivation test followed by the administration of desmopressin (synthetic ADH) can confirm the diagnosis if urine osmolality increases by more than 50%.

Nephrogenic Diabetes Insipidus (NDI):

• Pathophysiology: NDI occurs when the kidneys are unresponsive to ADH. It can be caused by genetic mutations (e.g., AVPR2 or AQP2 genes), chronic kidney disease, electrolyte imbalances (e.g., hypercalcemia or hypokalemia), medications (e.g., lithium), or post-obstructive uropathy.
• Symptoms: Similar to CDI but typically with a partial response to fluid deprivation.
• Diagnosis: Persistent low urine osmolality despite normal or high plasma ADH levels. A water deprivation test may not significantly improve urine osmolality even after desmopressin administration.

Dipsogenic Diabetes Insipidus:

• Pathophysiology: Excessive fluid intake due to abnormal thirst mechanisms (often psychogenic), leading to suppression of ADH and subsequent polyuria.
• Symptoms: Polyuria and polydipsia, but without the hypernatremia seen in CDI or NDI.
• Diagnosis: Water deprivation test shows normal ADH response but high water intake history, often psychiatric assessment needed.

Gestational Diabetes Insipidus:

• Pathophysiology: Occurs during pregnancy due to increased metabolism of ADH by the enzyme vasopressinase, produced by the placenta. Usually resolves postpartum.
• Symptoms: Symptoms similar to CDI but develop or worsen during pregnancy.
• Diagnosis: High plasma osmolality with low urine osmolality; response to desmopressin confirms the diagnosis.

Clinical Manifestations:

• Polyuria: Can exceed 10-20 liters per day in severe cases.
• Polydipsia: Compensatory response to polyuria to maintain fluid balance.
• Nocturia: Common in all forms of DI.
• Signs of Dehydration: If fluid intake is inadequate, signs such as dry mucous membranes, hypotension, tachycardia, and hypernatremia may develop.

Diagnostic Approach:

History and Physical Examination: Assess symptoms, medication use, recent head injuries, or history of psychiatric conditions.

Laboratory Tests:

• Serum Electrolytes and Osmolality: Hypernatremia (inadequate fluid intake) and elevated plasma osmolality (>295 mOsm/kg).
• Urine Osmolality: Low (<300 mOsm/kg) even in the presence of hypernatremia.

Water Deprivation Test: Monitors urine osmolality after fluid restriction; helps differentiate between CDI, NDI, and primary polydipsia.

Desmopressin Challenge Test: CDI shows increased urine osmolality after desmopressin, whereas NDI shows little to no response.

Management:

Central Diabetes Insipidus:

• Desmopressin (DDAVP): First-line treatment; administered orally, intranasally, or parenterally. Dose titration based on urine output and serum sodium levels.
• Fluid Management: Ensure adequate oral hydration; in severe cases, intravenous fluids may be necessary.
• Treat Underlying Cause: Surgical removal of pituitary tumors, corticosteroids for autoimmune conditions, or treatment of infections.

Nephrogenic Diabetes Insipidus:

• Thiazide Diuretics: Help reduce polyuria by inducing mild volume depletion, which increases renal tubular water reabsorption.
• Amiloride: Used particularly if NDI is secondary to lithium use, as it reduces lithium entry into renal cells.
• Low-Salt and Low-Protein Diet: Helps minimize solute load and thus urine output.
• Treat Underlying Causes: Correct electrolyte imbalances or discontinue causative medications.

Dipsogenic DI:

• Behavioral Therapy: Addressing the underlying psychiatric disorder or abnormal thirst behavior.
• Desmopressin: Generally not used, as it can worsen hyponatremia in dipsogenic DI.

Gestational Diabetes Insipidus:

• Desmopressin: Safe and effective during pregnancy.
• Monitoring: Regularly check serum sodium and osmolality levels.

Complications:

• Dehydration: Severe dehydration can lead to hypernatremia, which, if untreated, may cause neurological symptoms such as confusion, seizures, or even coma.
• Electrolyte Imbalances: Particularly in NDI, due to chronic polyuria.
• Impact on Quality of Life: Frequent urination and excessive thirst can significantly affect daily activities and sleep.

Prognosis:

• Central DI: Often managed effectively with desmopressin, though lifelong treatment may be necessary.
• Nephrogenic DI: More challenging to treat due to the underlying kidney insensitivity to ADH; management focuses on minimizing symptoms and treating the cause.
• Dipsogenic and Gestational DI: Generally resolves with behavioral therapy or postpartum.

Diabetes insipidus is a disorder of water balance caused by ADH deficiency or insensitivity. Accurate diagnosis and differentiation of its types are essential for effective management.