21-Deoxycortisol
21-Deoxycortisol, also known as 11β,17α-dihydroxyprogesterone or as 11β,17α-dihydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid related to cortisol which is formed as a metabolite from 17α-hydroxyprogesterone via 11β-hydroxylase.
Marker of 21-hydroxylase deficiency
21-deoxycortisol is a marker of congenital [adrenal hyperplasia due to 21-hydroxylase deficiency], even in mild cases. It can be also used for newborn screening.The deficiency of the 21-hydroxylase enzyme leads to excess of 17α-hydroxyprogesterone, a 21-carbon steroid. This excess is accompanied by the accumulation of other C21 steroids, such as 21-deoxycortisol, which is formed by the 11β-hydroxylation of 17α-hydroxyprogesterone via 11β-hydroxylase. The build-up of 21-deoxycortisol in patients with congenital adrenal hyperplasia have been described since at least 1955, this steroid was then called "21-desoxyhydrocortisone". Unlike 17α-hydroxyprogesterone, 21-deoxycortisol is not produced in the gonads and is uniquely adrenal-derived. Hence, 21-deoxycortisol is a more specific biomarker of 21-hydroxylase deficiency than is 17α-hydroxyprogesterone.
The corticosteroid activity of 21-deoxycortisol is lower than that of cortisol.
As 21-deoxycortisol can be at high levels in congenital adrenal hyperplasia, and it has structural similarity to cortisol, it can cross-react in immunoassays, resulting in a falsely normal or high cortisol result, when the true cortisol is actually low. Whereas immunoassays can suffer from cross-reactivity due to interactions with structural analogues, the selectivity offered by liquid chromatography-tandem mass spectrometry has largely overcome these limitations. Hence, the use of LC-MS/MS instead of immunoassays in cortisol measurement aims to provide greater specificity.
Besides 21-deoxycortisol, another C21 steroid, 21-deoxycorticosterone, has been proposed as a marker for 21-hydroxylase deficiency, but this marker did not gain acceptance due to the fact that testing for the levels of this steroid is not routinely offered by diagnostic laboratories.