11deoxycortisol

11-deoxycortisol is a corticosteroid intermediate in the biosynthesis of cortisol, produced in the adrenal cortex. It forms from 17-hydroxyprogesterone through the action of 21-hydroxylase (CYP21A2) and is subsequently converted to cortisol by 11β-hydroxylase (CYP11B1). Thus, it lies downstream of 17-hydroxyprogesterone and upstream of cortisol in the classical glucocorticoid pathway.

Biochemical role and activity: 11-deoxycortisol is a precursor rather than a primary active hormone. It has only weak glucocorticoid activity compared with cortisol, and its physiological effects, if any, are largely overshadowed by cortisol when the pathway is functioning normally. It serves mainly as an intermediate that must be efficiently converted to cortisol to sustain normal glucocorticoid signaling.

Clinical significance: The levels of 11-deoxycortisol are diagnostically informative in disorders of adrenal steroidogenesis. In 11β-hydroxylase deficiency, the block prevents conversion of 11-deoxycortisol to cortisol, leading to accumulation of 11-deoxycortisol and the related mineralocorticoid precursor 11-deoxycorticosterone, with features including hypertension and hypertension-related hypokalemia. In contrast, 21-hydroxylase deficiency predominantly elevates upstream substrates such as 17-hydroxyprogesterone, with low cortisol production. Measurement of 11-deoxycortisol can aid in distinguishing between these conditions under stimulation testing.

Measurement and analytical context: 11-deoxycortisol is quantified in plasma or serum, often by LC-MS/MS or immunoassays, as part of comprehensive steroid panels or ACTH stimulation tests in suspected congenital adrenal hyperplasia.