Mechanisms of Hypouricemia in the Syndrome of Inappropriate Secretion of Antidiuretic Hormone

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Abstract
Hypouricemia seen with hyponatremia related to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) results from an increase in uric acid renal clearance. We studied the mechanism of the increase of uric acid excretion in 6 SIADH patients through pyrazinamide (PZA), which decreases tubular secretion of uric acid, and sulfinpyrazone (SPZ) which decreases post-secretory reabsorption of uric acid. 3 g of PZA decreased the absolute uric acid excretion from 428 ± 244 to 105 ± 47 μg/min (mean ± SD, p < 0.01), and 300 mg of SPZ increased the uric acid to creatinine clearance ratio from 0.31 ± 0.05 to 0.52 ± 0.05 mg/dl glomerular filtration rate (mean ± SEM, p < 0.001), which represent an increment about half of that observed in the control group. The increase of uric acid clearance in SIADH seems to result from a decrease in the post-secretory reabsorption of uric acid. After SPZ, we saw a decrease of natriuresis from 5.6 ± 1.4 to 1.8 ± 0.3 mmol/h (p < 0.001), without any change of urinary flow or urinary potassium excretion.

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