Definition

Diabetes insipidus (DI) reflects the absence of antidiuretic hormone (ADH) owing to the destruction of the posterior pituitary gland (neurogenic DI) or failure of the renal tubules to respond to ADH (nephrogenic DI).

Pathophysiology

Common causes of neurogenic DI include severe head trauma, neurosurgical procedures (trauma to the median eminence, pituitary surgery), infiltrating pituitary lesions, and brain tumors. DI that develops after pituitary surgery is usually transient and often resolves in 5 to 7 days.

Nephrogenic DI may occur in association with an X-linked genetic mutation, hypercalcemia, hypokalemia, and medication-induced nephrotoxicity. Ethanol, demeclocycline, phenytoin, chlorpromazine, and lithium all inhibit the action of ADH or its release.

Clinical manifestations

The hallmark of DI is polyuria. The inability to produce concentrated urine results in dehydration and hypernatremia. The syndrome is characterized by a urine osmolarity less than 300 mOsm/L, urine specific gravity less than 1.010, and urine volumes greater than 30 mL/kg each day. The tremendous urinary water loss produces serum osmolarities greater than 290 mOsm/L and serum sodium concentrations greater than 145 mEq/L. Neurologic symptoms of hypernatremia and neuronal dehydration may be present and include hyperreflexia, weakness, lethargy, seizures, and coma.

The thirst mechanism assumes a primary role in maintaining water balance in awake patients with DI. Ingestion of large volumes of water prevents hyperosmolarity and life-threatening dehydration.