The symptoms of the disease are intense thirst, especially with a craving for ice water, with the volume of ingested fluid varying from 2 L to 20 L daily, and polyuria, with large urine volumes and low urine specific gravity (usually less than 1.006 with ad libitum fluid intake). The urine is otherwise normal. Partial diabetes insipidus presents with less intense symptoms and should be suspected in patients with enuresis. Most patients with diabetes insipidus are able to maintain fluid balance by continuing to ingest large volumes of water. However, in patients without free access to water or with a damaged hypothalamic thirst center and altered thirst sensation, diabetes insipidus may present with hypernatremia and dehydration. Diabetes insipidus is aggravated by administration of high-dose corticosteroids, which increases renal free water clearance.
Diagnosis of central diabetes insipidus is a clinical one; there is no single diagnostic laboratory test. Evaluation should include a 24-hour urine collection for volume and creatinine. A urine volume of less than 2 L/24 h (in the absence of hypernatremia) rules out diabetes insipidus. The patient can be tested during ad libitum fluid intake. A random urine is tested for osmolality. Blood testing includes plasma vasopressin and serum glucose, urea nitrogen, calcium, potassium, sodium, and uric acid.
Plasma AVP levels are usually low (below 1 pg/mL) with both central diabetes insipidus and primary polyuria, whereas plasma AVP levels are normal or elevated (more than 2.5 pg/mL) with nephrogenic diabetes insipidus. Plasma osmolality of 300 mOsm/kg or more implies either central or nephrogenic diabetes insipidus, whereas plasma osmolality of 280 mOsm/kg or less implies primary polydipsia as the diagnosis. Urine osmolality is low (300 mOsm/L or lower) in all three polyuric conditions and is not a helpful test. Hyperuricemia occurs frequently with both central and nephrogenic diabetes insipidus, whereas it is uncommon with primary polydipsia. In central and nephrogenic diabetes insipidus, the reduced vasopressin stimulation of the renal V1 receptor causes a reduction in the renal tubular clearance of urate.
A supervised “vasopressin challenge test” may be done: Desmopressin acetate 0.05–0.1 mL (5–10 mcg) intranasally (or 1 mcg subcutaneously or intravenously) is given, with measurement of urine volume for 12 hours before and 12 hours after administration. A serum sodium is obtained at baseline, 12 hours after the desmopressin, and immediately if symptoms of hyponatremia develop. Patients with central diabetes insipidus notice a distinct reduction in thirst and polyuria; serum sodium usually remains normal. The dosage of desmopressin is doubled if the response is marginal. In patients with primary polydipsia, a desmopressin challenge causes no significant reduction in polydipsia. Patients with nephrogenic diabetes insipidus show no response in polydipsia or urine volume.
Another test to distinguish central diabetes insipidus from primary polydipsia involves the carefully supervised hypertonic 3% saline-stimulated measurement of plasma copeptin, the C-terminal fragment of pre-pro-arginine vasopressin. Hypertonic 3% saline is administered intravenously as a 250 mL bolus, followed by a continuous infusion rate of 0.15 mL/kg/min. Plasma sodium is measured stat every 30 minutes; when the plasma sodium level reaches 150 mmol/L, blood is drawn for plasma copeptin. A level 4.9 pmol/L or less helps confirm the diagnosis of central diabetes insipidus.
Distinguishing central diabetes insipidus from primary polydipsia usually requires an MRI of the pituitary and hypothalamus. The normal posterior “bright spot” seen on the MRI T1-weighted image is undetectable or small with central diabetes insipidus, whereas it is normal in primary polydipsia and nephrogenic diabetes insipidus. MRI can also detect pathology responsible for central diabetes insipidus. Hypothalamic lesions may be visible; if the pituitary stalk is thickened, the cause of diabetes insipidus may be Langerhans cell histiocytosis, sarcoidosis, or lymphocytic hypophysitis.