Correspondence

Association of Interleukin-6 and Hypoaldosteronism in Patients with Cancer

N Engl J Med 1996; 334:473-474February 15, 1996

Article

To the Editor:

Patients with cancer may have a variety of metabolic and immunologic abnormalities that are thought to be caused by different humoral factors secreted by the tumors and are called paraneoplastic syndromes.1 We have seen several patients with cancer with unexplained hyperkalemia that we attributed to a paraneoplastic process.

Among 82 patients with cancer who were admitted to our hospital in 1993, 3 were identified with persistent hyperkalemia that could not be attributed to renal failure, pseudohyperkalemia, or drugs.2,3 These three patients underwent detailed studies of renal function, electrolyte metabolism, and the renin–angiotensin–aldosterone system and had measurements of plasma concentrations of interleukin-6,4 tumor necrosis factor α (TNF-α), and interleukin-1β.

The patients' clinical characteristics and laboratory data are summarized in Table 1Table 1Characteristics of Three Patients with Cancer-Related Hyperkalemia.. All three had reduced urinary potassium excretion, low plasma aldosterone concentrations, and elevated plasma renin activity. In response to furosemide, plasma renin activity at least doubled, but the increase in plasma aldosterone concentrations was subnormal. Basal and corticotropin-stimulated serum cortisol concentrations were normal. Thus, aldosterone secretion was selectively impaired. All three patients had high plasma interleukin-6 concentrations. In Patient 3, the plasma interleukin-6 concentration decreased and plasma renin activity, the plasma aldosterone concentration, and the serum potassium concentration became normal during successful antitumor chemotherapy and became abnormal again when the tumor recurred. In contrast, plasma TNF-α and interleukin-1β concentrations were normal in all three patients. In in vitro experiments with freshly isolated bovine zona glomerulosa cells,5 recombinant interleukin-6 (>5 ng per milliliter) inhibited (P = 0.003) the stimulatory effect of angiotensin II (10-⁸ M) or potassium chloride (6.5 mmol per liter) on aldosterone release in a concentration-dependent manner.

In conclusion, we have identified three patients with cancer-related hyperreninemic hypoaldosteronism associated with high plasma interleukin-6 concentrations. Because antitumor therapy reduced plasma interleukin-6 concentrations and improved the hyperkalemia in one patient and because interleukin-6 inhibits the secretion of aldosterone by adrenal tissue in vitro, we hypothesize that secretion of interleukin-6 by the tumors was responsible for the hypoaldosteronism in these patients.

Ung-il Chung, M.D.
Yuji Tanaka, M.D
Toshiro Fujita, M.D
University of Tokyo School of Medicine, Tokyo 112, Japan

5 References

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Citing Articles (1)

Citing Articles

1. 1

   Kimiharu Uozumi, Atae Utsunomiya, Shuichi Hanada, Terukatsu Arima. (1997) Interleukin-6 and cancer-related hypoaldosteronism. American Journal of Hematology 54:2, 171-171a
   CrossRef