IMPAIRMENT OF 11-BETA-HYDROXYLASE BUT NOT 21-HYDROXYLASE IN ADRENAL INCIDENTALOMAS

Recent reports have shown an exaggerated response of 17-hydroxyprogest erone in up to 70% of patients with incidentally detected adrenal aden omas ('incidentalomas'), This has been explained by pre-existing 21-hy droxylase deficiency which may be a pathogenetic factor in the develop ment of adrenal tumours. However, other defects in steroidogenesis, su ch as mild 11 beta-hydroxylase deficiency, could also result in increa sed 17-hydroxyprogesterone secretion. We therefore studied the glucoco rticoid and mineralocorticoid pathways in patients with adrenal 'incid entalomas' by measuring multiple adrenal steroids before and after 1-2 4 ACTH stimulation, Twenty patients with adrenal 'incidentalomas' (14 females, 6 males) and 27 healthy controls (14 females, 13 males) were studied. All subjects underwent a 1-24 ACTH stimulation test (250 mu g i.v.) with determination of progesterone, 11-deoxycorticosterone, cor ticosterone, 17-hydroxyprogesterone, 11-deoxycortisol and cortisol at 0 and 60 min, AU steroids were measured by RIA after extraction and HP LC. Patients with 'incidentalomas' had higher stimulated concentration s of 17-hydroxyprogesterone (21.6+/-8.4 vs 4.2+/-0.3 nmol/l; P less th an or equal to 0.001), 11-deoxycortisol (8.1+/-1.2 vs 3.6+/-0.3 nmol/l ; P less than or equal to 0.001), progesterone (8.28+/-2.82 vs 1.08+/- 0.15 nmol/l; P less than or equal to 0.002) compared with controls. In contrast, cortisol and corticosterone (2.1+/-0.39 vs 0.78+/-0.12 nmol /l; P=0.002) compared with controls, in contrast, cortisol and cortico sterone concentrations were not different. There was evidence for impa irment of 11 beta-hydroxylase activity by an increased 11-deoxycortiso l/cortisol ratio (0.012+/-0.003 vs 0.005+/-0.001 in controls; P=0.002) and 11-deoxycorticosterone/corticosterone ratio (0.04+/-0.003 vs 0.01 5+/-0.003; P=0.003). The conclusions reached were that patients with a drenal 'incidentalomas' have increased responses of precursors of the mineralocorticoid and glucocorticoid pathway including 17-hydroxyproge sterone after stimulation with ACTH. This seems to be caused by impair ment of 11 beta-hydroxylase activity rather than by impaired 21-hydrox ylase activity in these tumours.