Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women

A prospective study

Ricardo Azziz, Luis A. Hincapie, Eric S. Knochenhauer, Didier Dewailly, Liesl Fox, Larry R. Boots

Research output: Contribution to journalArticle

168 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)915-925
Number of pages11
JournalFertility and sterility
Volume72
Issue number5
DOIs
StatePublished - Nov 1 1999

Fingerprint

17-alpha-Hydroxyprogesterone
Steroid 21-Hydroxylase
Hyperplasia
Prospective Studies
Hyperandrogenism
Cosyntropin
Follicular Phase
Tertiary Healthcare
Menstrual Cycle
Ovulation
Outcome Assessment (Health Care)
Sensitivity and Specificity

Keywords

  • 21-hydroxylase
  • Adrenal
  • Adrenal hyperplasia
  • Androgens
  • Hirsutism

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women : A prospective study. / Azziz, Ricardo; Hincapie, Luis A.; Knochenhauer, Eric S.; Dewailly, Didier; Fox, Liesl; Boots, Larry R.

In: Fertility and sterility, Vol. 72, No. 5, 01.11.1999, p. 915-925.

Research output: Contribution to journalArticle

Azziz, Ricardo ; Hincapie, Luis A. ; Knochenhauer, Eric S. ; Dewailly, Didier ; Fox, Liesl ; Boots, Larry R. / Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women : A prospective study. In: Fertility and sterility. 1999 ; Vol. 72, No. 5. pp. 915-925.
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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.",
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T2 - A prospective study

AU - Azziz, Ricardo

AU - Hincapie, Luis A.

AU - Knochenhauer, Eric S.

AU - Dewailly, Didier

AU - Fox, Liesl

AU - Boots, Larry R.

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N2 - 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.

AB - 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.

KW - 21-hydroxylase

KW - Adrenal

KW - Adrenal hyperplasia

KW - Androgens

KW - Hirsutism

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