Apparent activities of 21-hydroxylase, 17 alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas

Objective: An increased response of 17-hydroxyprogesterone to ACTH stimulat ion has been observed in adrenal incidentaloma and linked to an impairment of either 21-hydroxylase or of 11 beta-hydroxylase activity. To analyse thi s question further, we investigated the steroidogenic pathways in a series of 17 adrenal incidentalomas. Design and Patients: 17 patients (7 women, 10 men: mean age, 62 +/- 12 year s) with non-histologically analyzed adrenal incidentalomas were prospective ly evaluated. Methods: The following variables were investigated: 24-h urinary methanephr ines and free cortisol excretion: plasma levels of ACTH and dehydroepiandro sterone; overnight dexamethasone suppression test: 1-24 ACTH stimulation te st with measurement of: cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, aldosterone, 11-deoxycorticosterone, progesterone, 17-hydroxypregnenolone, Delta 4-androstenedione, dehydroepiandrosterone and 21-deoxycortisol. Results: Discordant features of subclinical hypercorticism were noted in on e case. No patient had dehydroepiandrosterone sulfate levels in the normal range for his or her age. Peak 17-hydroxyprogesterone and peak 21-deoxycort isol disclosed impairment of 21-hydroxylase in 11 and 10 cases respectively An increased 11-deoxycortisol/cortisol ratio identified reduced activity o f 11 beta-hydroxylase in 11 patients. Eight patients displayed features of mild 17,20-lyase impairment, which was related to 21-hydroxylase dysfunctio n. Whereas only 2 patients showed no enzyme modification, 9 displayed alter ations of at least two pathways. Conclusion: In our hands, a combination of enzyme dysfunction was frequentl y observed. Shared biochemical mechanisms could explain combined 17,20-lyas e and 21-hydroxylase alterations, whereas coexistence of 21-hydroxylase (pa rticularly when based on peak 21-deoxycortisol) and 11 beta-hydroxylase is more puzzling.