Diabetes Insipidus (DI)

Key Features

• Central DI is an inability to synthesize and release vasopressin

• Without vasopressin, the kidneys cannot concentrate urine, causing excessive urinary water loss

• Most common causes

  • Midline defects (septo-optic dysplasia, holoprosencephaly)

  • Trauma (surgery, injury)

  • Infiltrative/neoplastic disease (tumors such as craniopharyngioma, germinoma, Langerhans cell histiocytosis, sarcoidosis)

  • Infectious (meningitis)

  • Idiopathic

• Traumatic DI often has three phases

  • Initially caused by edema in the hypothalamus or pituitary area

  • In 2–5 days, unregulated release of vasopressin from dying neurons causes the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

  • Finally, permanent DI occurs if a sufficient number of vasopressin neurons are destroyed

• Of note, germinomas often present with DI, whereas DI in craniopharyngioma is more often the result of neurosurgical intervention

Clinical Findings

• Onset is characterized by polyuria, nocturia, enuresis, and intense thirst, usually with a preference for cold water

• Hypernatremia, hyperosmolality, and dehydration occur if insufficient fluid intake does not keep up with urinary losses

• In infants, symptoms may also include failure to thrive, vomiting, constipation, and unexplained fevers

• Severe dehydration, circulatory collapse, and seizures may be presenting symptoms in some infants

Diagnosis

• Polydipsia, polyuria (> 2 L/m²/d), nocturia, dehydration, and hypernatremia

• Inability to concentrate urine after fluid restriction (urine specific gravity < 1.010; urine osmolality < 300 mOsm/kg)

• Plasma osmolality > 300 mOsm/kg with urine osmolality < 600 mOsm/kg

• Low plasma vasopressin with antidiuretic response to exogenous vasopressin

• DI is confirmed when serum hyperosmolality is associated with urine hypo-osmolarity

• Germinomas and other infiltrative diseases are often associated with pituitary stalk thickening on MRI

Treatment

• Central DI is treated with oral or intranasal desmopressin acetate (DDAVP)

• Children hospitalized with acute-onset DI can be managed with intravenous or subcutaneous vasopressin

• Due to the amount of antidiuresis, electrolytes should be closely monitored to avoid water intoxication

• Infants should not be treated with DDAVP, since their primary source of nutrition is through liquid calories and this combination can result in water intoxication

• For this reason, infants are treated with extra free water to maintain normal hydration

• A formula with a low renal solute load and chlorothiazides may be helpful in infants with central DI