21-Deoxycortisol, also known as 11ò,17ñ-dihydroxyprogesterone or as 11ò,17ñ-dihydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid related to cortisol (11ò,17ñ,21-trihydroxyprogesterone) which is formed as a metabolite from 17ñ-hydroxyprogesterone via 11ò-hydroxylase.
21-deoxycortisol is a marker of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, even in mild (non-classic) cases. It can be also used for newborn screening.
The deficiency of the 21-hydroxylase enzyme leads to excess of 17ñ-hydroxyprogesterone, a 21-carbon (C<sub>21</sub>) steroid. This excess is accompanied by the accumulation of other C<sub>21</sub> steroids, such as 21-deoxycortisol, which is formed by the 11ò-hydroxylation of 17ñ-hydroxyprogesterone via 11ò-hydroxylase (CYP11B1). 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 17ñ-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 17ñ-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 (LC-MS/MS) 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 C<sub>21</sub> steroid, 21-deoxycorticosterone (11ò-hydroxyprogesterone), 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.