Vasopressin Function in the Syndrome of Inappropriate Antidiuresis

Abstract

In 1938 Winkler & Crankshaw (1) described a group of patients who had hypochloremia and excessive urinary excretion of chloride despite appar­ ently normal kidneys and adrenal glands at autopsy. Subsequently other investigators reported patients with hyponatremia and urinary sodium wasting (2-5). In 1957, Schwartz et al (6) described similar findings in association with impaired urinary dilution in two patients with broncho­ genic carcinoma. They concluded from indirect evidence that the syndrome was due to inappropriate secretion of the antidiuretic hormone, arginine vasopressin. It is now recognized that the syndrome of inappropriate anti­ diuresis (SIAD) occurs in a great variety of malignant and nonmalignant diseases, most commonly those involving the central nervous system and lungs (Table 1) (7-51). The pathophysiology of this syndrome has been well delineated and reviewed elsewhere (7,8). Briefly, Schwartz and Bartter originally deduced from earlier studies of the effect of exogenous antidiuretic hormone in normal humans (52) that the syndrome resulted from inappropriate secre­ tion of antidiuretic hormone in the face of excessive water intake. This constellation of defects results in hyponatremia due to dilution and exces­ sive urinary excretion of sodium caused by the water retention. Hence, the cardinal features of SIAD as defined by Bartter & Schwartz (7) are (a) hyponatremia with corresponding hypoosmolality of the plasma, (b) osmo­ lality of the urine greater than that appropriate for concomitant plasma