Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas.
OBJECTIVE
An increased response of 17-hydroxyprogesterone to ACTH stimulation has been observed in adrenal incidentaloma and linked to an impairment of either 21-hydroxylase or of 11beta-hydroxylase activity. To analyse this question further, we investigated the steroidogenic pathways in a series of 17 adrenal incidentalomas.


METHODS
17 patients (7 women, 10 men; mean age, 62 +/- 12 years) with non-histologically analyzed adrenal incidentalomas were prospectively evaluated.


METHODS
The following variables were investigated: 24-h urinary methanephrines and free cortisol excretion; plasma levels of ACTH and dehydroepiandrosterone; overnight dexamethasone suppression test; 1-24 ACTH stimulation test with measurement of: cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, aldosterone, 11-deoxycorticosterone, progesterone, 17-hydroxypregnenolone, Delta4-androstenedione, dehydroepiandrosterone and 21-deoxycortisol.


RESULTS
Discordant features of subclinical hypercorticism were noted in one case. No patient had dehydroepiandrosterone sulfate levels in the normal range for his or her age. Peak 17-hydroxyprogesterone and peak 21-deoxycortisol disclosed impairment of 21-hydroxylase in 11 and 10 cases respectively. An increased 11-deoxycortisol/cortisol ratio identified reduced activity of 11beta-hydroxylase in 11 patients. Eight patients displayed features of mild 17,20-lyase impairment, which was related to 21-hydroxylase dysfunction. Whereas only 2 patients showed no enzyme modification, 9 displayed alterations of at least two pathways.


CONCLUSIONS
In our hands, a combination of enzyme dysfunction was frequently observed. Shared biochemical mechanisms could explain combined 17,20-lyase and 21-hydroxylase alterations, whereas coexistence of 21-hydroxylase (particularly when based on peak 21-deoxycortisol) and 11beta-hydroxylase is more puzzling.
Sadoul
J L
JL
Service de Diabétologie-Endocrinologie, Hôpital Pasteur, CHU de Nice, France. jl.sadoul@wanadoo.fr
Kézachian
B
B
Altare
S
S
Hadjali
Y
Y
Canivet
B
B
D006907:17-alpha-Hydroxypregnenolone / Q000097:blood; D000236:Adenoma / Q000201:enzymology*; D000310:Adrenal Gland Neoplasms / Q000201:enzymology*; D000311:Adrenal Glands / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000450:Aldosterone / Q000097:blood; D000735:Androstenedione / Q000097:blood; D003350:Cortodoxone / Q000097:blood; D003687:Dehydroepiandrosterone / Q000097:blood; D003900:Desoxycorticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D011374:Progesterone / Q000097:blood; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013255:Steroid 21-Hydroxylase / Q000378:metabolism*
D005938:Glucocorticoids; D006907:17-alpha-Hydroxypregnenolone; D000735:Androstenedione; D003900:Desoxycorticosterone; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D011374:Progesterone; C003556:21-deoxycortisol; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D012083:Renin; D003350:Cortodoxone; D006854:Hydrocortisone