Motivation: In my brief experience as an intern, most patients predictably have two conditions. One is a mild anemia (which implies, of course, that you need to have ordered iron, ferritin, folate, and B12 before morning rounds). The second condition is hyponatremia. I am not talking about sodium level of 120 but rather about the sodium level of 131. Since the causes of hyponatremia are so many, there is often no good reflex testing to click. I was recently told that uric acid is often low in hyponatremia from SIADH. How sensitive is hypourecemia for hyponatremia?
Paper: Beck, Laurence, "Hypouricemia in the Syndrome of Inappropriate Secretion of Antidiuretic Hormone". NEJM (1979) 301: 528-30.
Methods: A single person review of records of patients examined by the author (in the grand old tradition). Over a period of 18 months, patients with hyponatremia (defined as less than 130 mM) without renal failure (Cr<2.0) and not on diuretics were included in the study. Patients were labeled as having SIADH if they had serum osmolality less than 270 mOsm with urine osmolality greater than 250 mOsm. Also excluded were patients who were overtly hypervolemic (judged by edema), hypovolemic, or had signs of glucocorticoid deficiency.
Results:
Subjects: In the 18 month period, 49 patients were evaluated for hyponatremia. 19 patients were excluded for lack of uric acid measurement. Seventeen patients met criteria for SIADH wile the remaining 13 patients had euvolemic hyponatremia without SIADH.
Uric Acid Levels: The mean uric acid level in patients with SIADH was 2.9 mg/dL while the patients in the other group had mean level of 7.7 mg/dL (p<0.001). Only one patient with SIADH had uric acid level greater than 4 mg/dL. All patients without SIADH had uric acid concentration greater than 5 mg/dL. In seven patients with SIADH, when fluid restricted, uric acid levels rose to a mean level of 5.2 mg/dL from previous mean of 2.8 mg/dL.
Clearance of Uric Acid: In three patients, clearance of uric acid was measured by 24 hour urine collection. During periods of hyponatremia from SIADH, the uric acid clearance was increased compared to period after water restriction indicating that overexcretion rather than underproduction was the cause of hypouricemia.
Discussion: The paper is old with many weaknesses like few subjects and lack of testing for hypothyroidism, but this is one of the original papers showing the utility of uric acid measurement in distinguishing SIADH. One of the key points is that in both hypovolemic and hypervolemic hyponatremia, uric acid is generally expected to be normal or higher than normal. This paper showed that in euvolemic hyponatremia, SIADH can generally be distinguished from other causes (the paper does not investigate the "other" etiologies) by measuring uric acid levels. What was so remarkable was the degree of difference in mean uric acid levels among patients with SIADH (mean of 2.9 mg/dL) and those with other causes (7.7 mg/dL). These findings have been replicated in some subsequent studies (though none have very large number of subjects). From now on, I think that uric acid level is a great test to send overnight to investigate euvolemic hyponatremia.
Paper: Beck, Laurence, "Hypouricemia in the Syndrome of Inappropriate Secretion of Antidiuretic Hormone". NEJM (1979) 301: 528-30.
Methods: A single person review of records of patients examined by the author (in the grand old tradition). Over a period of 18 months, patients with hyponatremia (defined as less than 130 mM) without renal failure (Cr<2.0) and not on diuretics were included in the study. Patients were labeled as having SIADH if they had serum osmolality less than 270 mOsm with urine osmolality greater than 250 mOsm. Also excluded were patients who were overtly hypervolemic (judged by edema), hypovolemic, or had signs of glucocorticoid deficiency.
Results:
Subjects: In the 18 month period, 49 patients were evaluated for hyponatremia. 19 patients were excluded for lack of uric acid measurement. Seventeen patients met criteria for SIADH wile the remaining 13 patients had euvolemic hyponatremia without SIADH.
Uric Acid Levels: The mean uric acid level in patients with SIADH was 2.9 mg/dL while the patients in the other group had mean level of 7.7 mg/dL (p<0.001). Only one patient with SIADH had uric acid level greater than 4 mg/dL. All patients without SIADH had uric acid concentration greater than 5 mg/dL. In seven patients with SIADH, when fluid restricted, uric acid levels rose to a mean level of 5.2 mg/dL from previous mean of 2.8 mg/dL.
Clearance of Uric Acid: In three patients, clearance of uric acid was measured by 24 hour urine collection. During periods of hyponatremia from SIADH, the uric acid clearance was increased compared to period after water restriction indicating that overexcretion rather than underproduction was the cause of hypouricemia.
Discussion: The paper is old with many weaknesses like few subjects and lack of testing for hypothyroidism, but this is one of the original papers showing the utility of uric acid measurement in distinguishing SIADH. One of the key points is that in both hypovolemic and hypervolemic hyponatremia, uric acid is generally expected to be normal or higher than normal. This paper showed that in euvolemic hyponatremia, SIADH can generally be distinguished from other causes (the paper does not investigate the "other" etiologies) by measuring uric acid levels. What was so remarkable was the degree of difference in mean uric acid levels among patients with SIADH (mean of 2.9 mg/dL) and those with other causes (7.7 mg/dL). These findings have been replicated in some subsequent studies (though none have very large number of subjects). From now on, I think that uric acid level is a great test to send overnight to investigate euvolemic hyponatremia.
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