Apparent double defect in C11 beta and C21-steroid hydroxylation in congenital adrenal hyperplasia.

Some patients with either fully developed, mild or even hidden forms of congenital adrenal hyperplasia have both 21-deoxycortisol and increased 11-deoxycortisol in their blood and excrete "pregnanetriolone" and "tetrahydro-S" in their urine. The simultaneous presence of these compounds suggests two enzymic deficiencies, which are expressed in C21- and C11 beta-hydroxylases, respectively. However, these deficiencies have been inferred to derive from a single aberration in C11 beta-hydroxylase, whereby the enzyme acquires an affinity towards 21-deoxy precursors (i.e. 17-OH-progesterone) of cortisol and diminishes its activity against its regular 21-hydroxy intermediate 11-deoxycortisol. Depending on the severity of the aberration varying amounts of 21-deoxycortisol (expressing the aberrant 11 beta-hydroxylase) and of 11-deoxycortisol (expressing the normal 11 beta-hydroxylase) will be formed. An apparent two-level inhibition of cortisol biosynthesis will result from: (1) the low activity of normal 21-hydroxylase on the derivative 21-deoxycortisol, produced by the action of the aberrant 11 beta-hydroxylase, and (2) the low supply of 11-deoxycortisol for the regular but decreased (due to the aberration) 11 beta-hydroxylase. Thus a single defect will mimic at one and the same time a 21-hydroxylase and a 11 beta-hydroxylase deficiency.