Diabetes insipidus (DI) results from insufficient AVP production by the hypothalamus or from impaired AVP action in the kidney. AVP deficiency is characterized by production of large amounts of dilute urine. In central DI, insufficient AVP is released in response to physiologic stimuli. Causes include acquired (head trauma; neoplastic or inflammatory conditions affecting the hypothalamus/posterior pituitary), congenital, and genetic disorders, but almost half of cases are idiopathic. In gestational DI, increased metabolism of plasma AVP by an aminopeptidase (vasopressinase) produced by the placenta leads to a relative deficiency of AVP during pregnancy. Primary polydipsia results in secondary insufficiency of AVP due to physiologic inhibition of AVP secretion by excessive fluid intake. There are three main types: (1) dipsogenic DI with inappropriate thirst; (2) psychogenic DI often associated with psychosis or obsessive compulsive disorders; and (3) iatrogenic DI often caused by efforts to consume excess fluids for presumed health benefits. Nephrogenic DI is caused by AVP resistance at the level of the kidney; it can be genetic or acquired from drug exposure (lithium, demeclocycline, amphotericin B), metabolic conditions (hypercalcemia, hypokalemia), or renal damage.
Symptoms include polyuria, excessive thirst, and polydipsia, with a 24-h urine output of >50 mL/kg per day and a urine osmolality that is less than that of serum (<300 mosmol/kg; specific gravity <1.010). DI can be partial or complete; in the latter case the urine is maximally diluted (<100 mosmol/kg) and the daily urine output can reach 10–20 L. Clinical or laboratory signs of dehydration, including hypernatremia, occur only if the pt simultaneously has a thirst defect (not uncommon in pts with CNS disease) or does not have access to water. Other etiologies of hypernatremia are described in Chap. 1: Electrolytes.
DI must be differentiated from other etiologies of polyuria (Chap. 48: Azotemia and Urinary Abnormalities). Unless an inappropriately dilute urine is present in the setting of serum hyperosmolality, a fluid deprivation test is used to make the diagnosis of DI. This test should be started in the morning with careful supervision to avoid dehydration. Body weight, plasma osmolality, serum sodium, and urine volume and osmolality should be measured hourly. The test should be stopped when body weight decreases by 5% or plasma osmolality/sodium exceeds the upper limit of normal. If the urine osmolality is <300 mosmol/kg with serum hyperosmolality, desmopressin (0.03 µg/kg SC) should be administered with repeat measurement of urine osmolality 1–2 h later. An increase of >50% indicates severe pituitary DI, whereas a smaller or absent response suggests nephrogenic DI. Measurement of AVP levels before and after fluid deprivation may be helpful to distinguish central and nephrogenic DI. If AVP is normal or elevated (>1 pg/mL) and the concurrent urine osmolarity is low (<300 mosmol/L), the pt has nephrogenic DI and the only additional evaluation required is to determine the cause. Occasionally, hypertonic saline infusion may be required if fluid deprivation does not achieve the requisite level of hypertonic dehydration, but this should be administered with caution.
Pituitary DI can be treated with desmopressin (DDAVP) subcutaneously (1–2 µg once or twice per day), via nasal spray (10–20 µg two or three times a day), or orally (100–400 µg two or three times a day), with recommendations to drink to thirst. Symptoms of nephrogenic DI may be ameliorated by treatment with a thiazide diuretic and/or amiloride in conjunction with a low-sodium diet, or with prostaglandin synthesis inhibitors (e.g., indomethacin).
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