Congenital Adrenal Hyperplasia (CAH) Newborn Screening, Blood Spot
Second-tier testing of newborns with abnormal screening result for congenital adrenal hyperplasia
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Second-tier newborn screen
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Congenital adrenal hyperplasia (CAH) is a group of disorders caused by inherited defects in steroid biosynthesis, in particular, 21-hydroxylase deficiency (approximately 90% of cases), and 11-beta hydroxylase deficiency (approximately 5-8% of cases). The overall incidence of the classic form of 21-hydroxylase deficiency is approximately 1 in 16,000 worldwide. Individuals with CAH may present with life-threatening, salt-wasting crises in the newborn period and incorrect gender assignment of virilized females as a result of reduced glucocorticoids and mineralocorticoids and elevated 17-hydroxyprogesterone (17-OHP) and androgens. Hormone replacement therapy, when initiated early, enables a significant reduction in morbidity and mortality. Therefore, newborn screening for CAH is desirable and has been implemented in all 50 states.
Immunoassays are typically used to quantify 17-OHP as a marker for CAH. However, these immunoassays are hampered by cross-reactivity of the antibodies with other steroids, yielding a high rate of false-positive results. Tandem mass spectrometry allows for the simultaneous specific determination of 17-OHP and other steroids, such as androstenedione, cortisol, 11-deoxycortisol, and 21-deoxycortisol. Application of this technology to the determination of steroids in newborn screening blood spots significantly enhances the correct identification of patients with CAH and reduces the number of false-positive screening results when implemented as a second-tier analysis performed prior to reporting of initial newborn screen results.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Males: <7.1 ng/mL
Females: <4.1 ng/mL
(17 OHP + ANDROSTENEDIONE)/CORTISOL RATIO
Note: Abnormal (17 OHP + Androstenedione)/Cortisol Ratio: >2.5 is only applicable when 17-OHP is elevated
Findings of a 17-hydroxyprogesterone (17-OHP) value >7.0 ng/mL in males or >4.0 ng/mL in females, and a high (17-OHP + androstenedione)/cortisol ratio (controls: < or =2.5) are supportive of the initial abnormal newborn screening result.
Findings of an 11-deoxycortisol value >10.0 ng/mL or 21-deoxycortisol >1.6 ng/mL with elevated 17-OHP further support the abnormal newborn screening result and increase the diagnostic specificity. Clinical and laboratory follow-up is strongly recommended.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This is a screening test and, while it's positive predictive value is significantly higher than that of immunoassays (9.0% versus 0.5%), false-positive results can occur. Follow-up of abnormal results is necessary; perform OHPG / 17-Hydroxyprogesterone, Serum and DOC / 11-Deoxycortisol, Serum.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Antal Z, Zhou P: Congenital adrenal hyperplasia: diagnosis, evaluation and management. Pediatr Rev 2009 Jul;30(7):e49-57
2. Minutti CZ, Lacey JM, Magera MJ, et al: Steroid profiling by tandem mass spectrometry improves the positive predictive value of newborn screening for congenital adrenal hyperplasia. J Clin Endo Met 2004;89:3687-3693
3. Turcu AF, Auchus RJ: The next 150 years of congenital adrenal hyperplasia. J Steroid Biochem Mol Biol 2015 Jun 3 DOI:10.1016/j.jsbmb.2015.05.013 (Epub ahead of print)
4. Witchel SF, Azziz R: Congenital adrenal hyperplasia. Pediatri Adolesc Gynecol 2011;24:116-126