Exp Clin Endocrinol Diabetes 2002; 110(6): 272-276
DOI: 10.1055/s-2002-34589
Article

© Johann Ambrosius Barth

Furosemide and 11β-hydroxysteroid dehydrogenase activity, in man

M. Palermo1 , D. Armanini2 , C. H. L. Shackleton3 , G. Sorba4 , M. Cossu4 , E. Roitman3 , C. Scaroni2 , G. Delitala1
  • 1 Institute of Endocrinology, University of Sassari, Sassari, Italy
  • 2 Department of Medical and Surgical Sciences, Chair of Endocrinology, University of Padua, Italy
  • 3 Children's Hospital, Research Institute Oakland, CA, USA
  • 4 Division of Nephrology, SS Annunziata Hospital, Sassari, Italy
Further Information

Publication History

received 2 January 2002 first decision 2 March 2002

accepted 6 May 2002

Publication Date:
09 October 2002 (online)

Summary

Mineralocorticoid receptors possess the same affinity for aldosterone and for cortisol and preferential binding of aldosterone is modulated by the 11β-hydroxysteroid dehydrogenase (11β-OHSD) enzyme, which converts cortisol to its inactive metabolite cortisone. Several endogenous or exogenous compounds able to inhibit the enzyme have been described and, as a consequence, produce the syndrome of apparent mineralocorticoid excess (AME) characterized by hypertension, hypokalemia, volume repletion and suppression of the renin-angiotensin-aldosterone system. High doses of furosemide, a diuretic that works in the luminal surface of the thick ascending limb of Henle's loop, have been reported to inhibit 11β-OHSD activity to the same extent as licorice in vivo and in vitro, in rat.

The aim of our study was to verify the effect of the drug on 11β-OHSD activity in man at the doses currently used in clinical practice. We tested the activity of 11β-OHSD following both acute and protracted administration of furosemide. In the acute study, the drug was administered at low (40 mg i.v. in bolo) and high doses (infusion of 10 mg/kg bw i.v for six hours); the protracted furosemide administration consisted in 50 mg/day for 20 days, by mouth. The ratios between the cortisol metabolites tetrahydrocortisol plus allo-tetrahydrocortisol to tetra-hydrocortisone and urinary free cortisol to urinary free cortisone were used to measure the activity of 11β-OHSD. Urinary cortisol, cortisone and their metabolites were tested by a gas-chromatographic/mass spectrometric method.

Neither acute nor prolonged administration of furosemide did affect the activity of 11β-OHSD although the drug was able to modify plasma aldosterone and PRA secretion and to determine hypokalemia. Our results suggest that furosemide does not play a significant role in 11β-OHSD modulation in humans, at least at the dosage used in clinical practice.

References

M.D. Mario Palermo

Institute of Endocrinology

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I-07100 Sassari

Italy

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