MARSHAL P. FICHMAN, M.D.; JOHN E. BETHUNE, M.D., F.A.C.P.
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Twenty patients with all of the characteristics of the inappropriate antidiuretic hormone (ADH) syndrome were observed at the Los Angeles County General Hospital in the past 2 years. The varied causes, including chest lesions, central nervous system disorders, and unclassified causes and frequency, suggest that it is certainly not a rare syndrome. Bioassay for ADH in the majority of cases tested showed increased biologic activity in serums or tumors. The defect in acute water load excretion was correctable by intravenous diphenylhydantoin in the cases not due to autonomous tumor. Glucocorticoid administration failed to correct hyponatremia in patients with the syndrome as compared with patients with hyponatremia secondary to hypopituitarism. The failure of high doses of glucocorticoids to affect the syndrome suggests that, at least in patients with inappropriate or autonomous ADH secretion, glucocorticoids do not act as inhibitors of ADH release. Mineralocorticoids in high doses may correct the hyponatremia, and an "escape" phenomenon with a resumption of increased urinary sodium may ensue. Aldosterone excretion may be normal and important in minimizing sodium losses as shown by the inhibition of aldosterone-mediated sodium retention and aggrevation of the sodium loss by aldosterone inhibitors. Creatinine clearance was generally normal, and there was no correlation between variation in glomerular filtration rate and urine sodium excretion. The presence of normal creatinine clearance and aldosterone excretion with persistent urine sodium loss, in spite of hyponatremia, suggests that the sodium diuresis is due to some "third factor" other than increased glomerular filtration or hypervolemic inhibition of aldosterone. The mechanism of sodium loss in this syndrome appears to be similar to the escape phenomenon occurring with high doses of mineralocorticoids and may be related to proximal tubular rejection of sodium secondary to an expanded intravascular volume.
FICHMAN MP, BETHUNE JE. The Role of Adrenocorticoids in the Inappropriate Antidiuretic Hormone Syndrome. Ann Intern Med. ;68:806–820. doi: 10.7326/0003-4819-68-4-806
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Published: Ann Intern Med. 1968;68(4):806-820.
Endocrine and Metabolism, Fluid and Electrolyte Disorders, Nephrology, Neurology.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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