Deficiency of Cortisol 11β-Ketoreductase — A New Metabolic Defect

Abstract

A deficiency of cortisol 11β-ketoreductase was observed in 2 patients with the syndrome of apparent mineralocorticoid excess and no evidence of oversecretion of any known steroid hormone. The syndrome is characterized by hypertension, hypokalemia and suppressed renin and ACTH despite low secretion of aldosterone, cortisol and other adrenocortical steroids. Excretion of 5α-reduced cortisol (DHF) is increased in the urinary free steroid fraction. The 11-ketoreductase deficiency was demonstrated by a markedly elevated ratio of urinary THF/THE (6-10). In normal children the THF/THE ratio is usually less than 1. The deficiency was further proven by demonstrating an inability to form tritiated water after infusion of 11α3H cortisol. In normal subjects and in the unaffected mother of a patient, 65-80% of 11α3H cortisol appeared as tritiated water. Speculation: In these patients the 11-ketoreductase deficiency produces an impairment of the metabolism of cortisol to cortisone, resulting in a prolonged cortisol half-life, suppression of ACTH and normal serum cortisol concentration. The enzyme defect protects the patient from adrenal insufficiency despite low cortisol secretion and may contribute to hypertension and hyporeninemia because of formation of excess DHF which has mineralocorticoid activity.

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New, M., Bradlow, L., Fishman, J. et al. Deficiency of Cortisol 11β-Ketoreductase — A New Metabolic Defect. Pediatr Res 12, 1084 (1978). https://doi.org/10.1203/00006450-197811000-00017

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