Failure of cortisone acetate treatment in congenital adrenal hyperplasia because of defective 11 beta-hydroxysteroid dehydrogenase reductase activity

Congenital adrenal hyperplasia in children is often treated with cortisone acetate and fludrocortisone, It is known that certain patients with congeni tal adrenal hyperplasia require very high substitution doses of cortisone a cetate, and a few patients do not respond to this treatment at all. A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol ( P3) levels in urine were not suppressed during treatment with cortisone ace tate (65 mg/m(2) day), was examined. The activation of cortisone to cortiso l was assessed by measuring urinary metabolites of cortisone and cortisol. The patient's inability to respond to treatment with cortisone acetate was found to be caused by a low conversion of cortisone to cortisol, assumed to be secondary to low 11 beta-hydroxysteroid dehydrogenase activity (11-oxor eductase deficiency). All exons and exon/ intron junctions of the 11 beta-h ydroxysteroid dehydrogenase type 1 gene (HSD11L) were sequenced without fin ding any mutations. but a genetic lesion in the promoter or other regulator y regions cannot be ruled out. The deficient 11-oxoreductase activity seems to have been congenital, in this case, but can possibly be attributable to a down-regulation of the enzyme activity. The results support the use of h ydrocortisone, rather than cortisone acetate, for substitution therapy in a drenal insufficiency.