Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study.
OBJECTIVE
To prospectively establish the specificity, sensitivity, and positive predictive value (PPV) of a basal 17-hydroxyprogesterone (17-HP) level for the screening of 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) among hyperandrogenic women.


METHODS
Prospective observational trial.


METHODS
Tertiary care academic medical centers.


METHODS
Eight healthy controls, 20 patients with NCAH, and 284 consecutively seen patients with hyperandrogenism.


METHODS
All controls and patients with NCAH, and select patients with hyperandrogenism, underwent acute ACTH (1-24) stimulation.


METHODS
Specificity was determined by measuring 17-HP every other day during one menstrual cycle in 8 healthy women with normal ovulation (107 samples). Sensitivity was determined by measuring 17-HP between 7 and 9 A.M. and 3 and 5 P.M. on the same day in 20 patients with genetically confirmed NCAH. The PPV was determined by prospectively measuring 17-HP in 284 consecutively seen hyperandrogenic women at their initial evaluation. The diagnosis of NCAH was established by a stimulated 17-HP level of >10 ng/mL.


RESULTS
Among controls, 17-HP levels of <2, <3, and <4 ng/mL all had a specificity of 100% when obtained in the follicular phase; when obtained in the luteal phase, they had specificities of 53%, 82%, and 82%, respectively. Among patients with NCAH, 17-HP levels of >2, >3, and >4 ng/mL had sensitivities of 100%, 90%, and 90%, respectively, for the detection of the disorder when obtained in the morning, and sensitivities of 95%, 90%, and 85%, respectively, when obtained in the afternoon. Among the 284 consecutively seen hyperandrogenic women, the PPVs of the first and second 17-HP levels were 7.3% and 19% for a cutoff level of >2 ng/mL, 13% and 43% for a cutoff level of >3 ng/mL, and 33% and 40% for a cutoff level of >4 ng/mL, respectively.


CONCLUSIONS
A basal 17-HP level is a useful screening tool for NCAH. A cutoff level of 4 ng/mL has maximum specificity and PPV, with little loss in sensitivity if testing is performed in the morning and during the follicular phase. However, a lower cutoff level (e.g., 2 or 3 ng/mL) is preferable if testing is performed at odd hours of the day, as is common in many practices, and maximum sensitivity is desired.
Azziz
R
R
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, 35233-7333, USA.
Hincapie
L A
LA
Knochenhauer
E S
ES
Dewailly
D
D
Fox
L
L
Boots
L R
LR
D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism*; D000311:Adrenal Glands / Q000201:enzymology; D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology*; D001481:Basal Metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity
D019326:17-alpha-Hydroxyprogesterone