Central Diabetes Insipidus

Genetic abnormalities of the vasopressin gene on chromosome 20 are responsible for autosomal dominant forms of primary central diabetes insipidus, but many cases are idiopathic.

Central diabetes insipidus may also be secondary (acquired), caused by various lesions, including hypophysectomy, cranial injuries (particularly basal skull fractures), suprasellar and intrasellar tumors (primary or metastatic), Langerhans cell histiocytosis Langerhans Cell Histiocytosis Langerhans cell histiocytosis (LCH) is a proliferation of dendritic mononuclear cells with infiltration into organs locally or diffusely. Most cases occur in children. Manifestations may include... read more , lymphocytic hypophysitis, granulomas (sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more or tuberculosis Tuberculosis (TB) Tuberculosis is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial infection. Tuberculosis most commonly affects the lungs. Symptoms include... read more ), vascular lesions (aneurysm, thrombosis), and infections (encephalitis Encephalitis Encephalitis is inflammation of the parenchyma of the brain, resulting from direct viral invasion or occurring as a postinfectious immunologic complication caused by a hypersensitivity reaction... read more , meningitis Overview of Meningitis Meningitis is inflammation of the meninges and subarachnoid space. It may result from infections, other disorders, or reactions to drugs. Severity and acuity vary. Findings typically include... read more ).

Psychogenic polydipsia may present a difficult problem in differential diagnosis. Patients may ingest and excrete up to 6 L of fluid/day and are often emotionally disturbed. Unlike patients with central diabetes insipidus and nephrogenic diabetes insipidus, they usually do not have nocturia, nor does their thirst wake them at night. Continued ingestion of large volumes of water in this situation can lead to life-threatening hyponatremia Hyponatremia Hyponatremia is decrease in serum sodium concentration < 136 mEq/L (< 136 mmol/L) caused by an excess of water relative to solute. Common causes include diuretic use, diarrhea, heart failure... read more .

Patients with acute psychogenic water drinking are able to concentrate their urine during water deprivation. However, because chronic water intake diminishes medullary tonicity in the kidneys, patients with long-standing polydipsia are not able to concentrate their urine to maximal levels during water deprivation, a response similar to that of patients with partial central diabetes insipidus. However, unlike central diabetes insipidus, patients with psychogenic polydipsia show no response to exogenous vasopressin after water deprivation. This response resembles nephrogenic diabetes insipidus, except that basal vasopressin levels are low compared with the elevated levels present in nephrogenic diabetes insipidus. After prolonged restriction of fluid intake to ≤ 2 L/day, normal concentrating ability returns within several weeks.

Desmopressin, a synthetic analog of vasopressin with minimal vasoconstrictive properties, has prolonged antidiuretic activity, lasting for 12 to 24 hours in most patients, and may be administered intranasally, subcutaneously, IV, or orally. Desmopressin is the preparation of choice for both adults and children and is available as an intranasal solution in 2 forms. A dropper bottle with a calibrated nasal catheter has the advantage of delivering incremental doses from 5 to 20 mcg but is awkward to use. A spray bottle that delivers 10 mcg of desmopressin in 0.1 mL of fluid is easier to use but delivers a fixed quantity.

For each patient, the duration of action of a given dose must be established, because variation among individuals is great. The duration of action can be established by following timed urine volumes and osmolality. The nightly dose is the lowest dose required to prevent nocturia. The morning and evening doses should be adjusted separately. The usual dosage range in individuals >12 years is 10 to 40 mcg, with most requiring 10 mcg twice a day. For children age 3 months to 12 years, the usual dosage range is 2.5 to 10 mcg twice a day.

Overdosage can lead to fluid retention and decreased plasma osmolality, possibly resulting in seizures in small children. In such instances, furosemide can be given to induce diuresis. Headache may be a troublesome adverse effect but generally disappears if the dosage is reduced. Infrequently, desmopressin causes a slight increase in blood pressure. Absorption from the nasal mucosa may be erratic, especially when an upper respiratory infection or allergic rhinitis occurs. When intranasal delivery of desmopressin is inappropriate, it may be administered subcutaneously using about one tenth of the intranasal dose. Desmopressin may be used IV if a rapid effect is necessary (eg, for hypovolemia). With oral desmopressin, dose equivalence with the intranasal formulation is unpredictable, so individual dose titration is needed. The initial dose is 0.1 mg orally 3 times a day, and the maintenance dose is usually 0.1 to 0.2 mg 3 times a day.

Lypressin, a synthetic form of vasopressin given as a nasal spray, is no longer available.

Aqueous vasopressin 5 to 10 units subcutaneously or IM can be given to provide an antidiuretic response that usually lasts ≤ 6 hours. Thus, this drug has little use in long-term treatment but can be used in the initial therapy of unconscious patients and in patients with central diabetes insipidus who are undergoing surgery. Synthetic vasopressin can also be administered twice a day to 4 times a day as a nasal spray, with the dosage and interval tailored to each patient. Vasopressin tannate in oil 0.3 to 1 mL (1.5 to 5 units) IM may control symptoms for up to 96 hours.

At least 3 groups of nonhormonal drugs are useful in reducing polyuria:

These drugs have been particularly useful in partial central diabetes insipidus and do not cause the adverse effects of exogenous vasopressin.

Thiazide diuretics paradoxically reduce urine volume in partial and complete central diabetes insipidus (and nephrogenic diabetes insipidus), primarily as a consequence of reducing extracellular fluid (ECF) volume and increasing proximal tubular resorption. Urine volumes may fall by 25 to 50% with 15 to 25 mg/kg of chlorothiazide.

Chlorpropamide, carbamazepine, and clofibrate can reduce or eliminate the need for vasopressin in some patients with partial central diabetes insipidus. None are effective in nephrogenic diabetes insipidus. Chlorpropamide 3 to 5 mg/kg orally once or twice a day causes some release of vasopressin and also potentiates the action of vasopressin on the kidneys. Clofibrate 500 to 1000 mg orally twice a day or carbamazepine 100 to 400 mg orally twice a day is recommended for adults only. These drugs may be used synergistically with a diuretic. However, significant hypoglycemia may result from chlorpropamide.

Prostaglandin inhibitors (eg, indomethacin 0.5 to 1.0 mg/kg orally 3 times a day, although most nonsteroidal anti-inflammatory drugs [NSAIDs] are effective) are modestly effective. They may reduce urine volume, but generally by no more than 10 to 25%, perhaps by decreasing renal blood flow and glomerular filtration rate (GFR). Together with indomethacin, restriction of sodium intake and a thiazide diuretic help further reduce urine volume in nephrogenic diabetes insipidus.