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Significantly Higher Adrenocorticotropin-Stimulated Cortisol and 17-Hydroxyprogesterone Levels in 337 Consecutive, Premenopausal, Caucasian, Hirsute Patients Compared with Healthy Controls

Departments of Endocrinology (D.G., A.P.H., J.H., C.H., M.A.) and Clinical Chemistry (K.B.), Odense University Hospital, 5000 Odense C, Denmark

Address all correspondence and requests for reprints to: Dorte Glintborg, Odense University Hospital, Department of Endocrinology, Kløvervænget 10, 3, 5000 Odense C, Denmark. E-mail: dorte.glintborg{at}ouh.fyns-amt.dk.

Objective: To investigate whether elevated ACTH-stimulated 17-hydroxyprogesterone (17OHP) levels are caused by CYP21 genetic defects or by a general adrenal hyperresponsiveness in hirsute patients.

Methods: A total of 337 hirsute patients were evaluated by Ferriman-Gallwey score, serum testosterone, ACTH-stimulated 17OHP, and cortisol during the follicular phase. A cutoff value of 16 nmol/liter for maximum ACTH-stimulated 17OHP (M17OHP) responses was defined as the upper limit of the 95% confidence interval (CI) for the 97.5 percentile in 42 female controls. All patients were offered total screening of the CYP21 gene, and 252 healthy, premenopausal women with regular menses underwent genetic screening.

Results: Patients were divided into idiopathic hirsutism (IH) (n = 180) and polycystic ovary syndrome (PCOS) (n = 157) groups. M17OHP levels were significantly higher in IH [geometric mean value (nmol/liter ± 2 SD) 12.2 (4.6–32.3)] and PCOS [11.9 (5.3–27.2)] compared with controls [8.5 (5.1–14.2)] (P < 0.001). A similar percentage of IH and PCOS patients had elevated M17OHP (20.5 vs. 20.8%, not significant), and these also had significantly higher 30-min cortisol levels compared with controls (P < 0.05). The prevalence of CYP21 mutations in patients was 8.6% compared with 6.3% in controls (P = 0.38). Ten of 19 carriers had M17OHP levels below the cutoff limit.

Conclusion: The significantly higher ACTH-stimulated levels of cortisol and 17OHP in hirsute patients indicated adrenal hyperresponsiveness in IH and PCOS. CYP21-carrier status could not explain the observed high prevalence of abnormal ACTH-stimulated 17OHP levels in the hirsute population.

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