Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study.

Abstract

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.

DESIGN:

Prospective observational trial.

SETTING:

Tertiary care academic medical centers.

PATIENT(S):

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

INTERVENTION(S):

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

MAIN OUTCOME MEASURE(S):

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.

RESULT(S):

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.

CONCLUSION(S):

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.

• Authors: R Azziz, L A Hincapie, E S Knochenhauer, D Dewailly, L Fox, L R Boots
• Journal: Fertility and sterility (Fertil Steril) Vol. 72 Issue 5 Pg. 915-25 (Nov 1999) ISSN: 0015-0282 [Print] United States
• PMID: 10561000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 17-alpha-Hydroxyprogesterone

Topics

• 17-alpha-Hydroxyprogesterone (metabolism)
• Adrenal Glands (enzymology)
• Adrenal Hyperplasia, Congenital (enzymology)
• Basal Metabolism
• Case-Control Studies
• Female
• Humans
• Mass Screening (methods)
• Predictive Value of Tests
• Prospective Studies
• Sensitivity and Specificity