11-Deoxycorticosterone represents the last intermediate in the mineral corticoid pathway that has negligible mineral corticoid activity. It is converted by 11-beta-hydroxylase 2 (CYP11B2) or by 11-beta-hydroxylase 1 (CYP11B1) to the first mineral corticoids with significant activity, corticosterone. Corticosterone is in turn converted to 18-hydroxycorticosterone and finally to aldosterone, the most active mineral corticoid. Both of these reactions are catalyzed by CYP11B2, which, unlike its sister enzyme CYP11B1, also possesses 18-hydroxylase and 18-methyloxidase activity.
Measurement of 11-deoxycorticosterone and its glucocorticoid pendant, 11-deoxycortisol (also known as compound S), is aimed at diagnosing:
- CYP11B1 deficiency (associated with cortisol deficiency)
- The rarer CYP11B2 deficiency (no cortisol deficiency)
- The yet less common glucocorticoid-responsive hyperaldosteronism (where expression of the gene CYP11B2 is driven by the CYP11B1 promoter, thus making it responsive to adrenocorticotrophic hormone: ACTH rather than renin)
Cortisol should be measured in all cases of suspected CAH.
In the diagnosis of suspected 11-hydroxylae deficiency and glucocorticoid-responsive hyperaldosteronism, this test should be used in conjunction with measurements of 11-deoxycortisol, corticosterone, 18-hydroxycorticosterone, cortisol, renin, and aldosterone.