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Indication - Congenital adrenal hyperplasia
17-Hydroxyprogesterone (17-OHP)
Facility level:
2. Laboratory
Assay formats
Immunoassay
Status history
First added in 2022
Purpose type
Diagnosis, Monitoring
Purpose
To diagnose and monitor congenital adrenal hyperplasia (CAH) outside of the neonatal period (Not appropriate for screening)
Specimen types
Serum, Plasma
WHO prequalified or recommended products
N/A
WHO supporting documents
N/A
Technical specifications for procurements
None
Codes
ICD11 code: 5A71.01

Summary of evidence evaluation

CAH is a rare health problem, but it can be life-threatening if not diagnosed in a timely manner. The 17-OHP immunoassay has been developed for diagnosing this condition. In a clinical guideline, the assay is recommended for screening in newborns, and several countries have implemented this as part of their screening programme. However, the originator of this application provided no evidence (i.e. no systematic reviews, no primary studies) relating to diagnostic accuracy or clinical utility. Furthermore, the costs are unclear, and it is also unclear how this assay relates to other diagnostic tests.

Summary of SAGE IVD deliberations

The 17-OHP assay is intended to diagnose CAH. SAGE IVD members noted that the evidence for the use of the test in different settings was not well defined in this application. For example, 17-OHP is appropriate for diagnosing CAH outside of the neonatal period as well as other adrenal and ovarian issues in older persons. Moreover, some experts questioned whether the test was intended for screening or for diagnosis. One expert explained that this test is used to support the diagnosis of CAH outside of the neonatal period, to monitor CAH therapy, and to assess and manage hirsutism and infertility. The group noted that WHO and the United Nations Children’s Fund have referred to the unreliability of the test for screening for a range of pregnancy conditions. One member highlighted that using 17-OHP to screen in a neonatal setup generates 1–2% false positives in the best case, making it unfeasible. And for neonatal screening, spectroscopy or high-performance chromatography are the preferred modalities in any event. SAGE IVD acknowledged the limited evidence for the test within this application. However, the group saw value in this test. The experts acknowledged that using 17-OHP to diagnose CAH is appropriate and important for patients. Consequently, SAGE IVD decided to list the 17-OHP assay specifically to diagnose CAH outside of the neonatal period, but not to screen for it.

SAGE IVD recommendation

SAGE IVD recommended listing the 17-hydroxyprogesterone (17-OHP) test category in EDL 4 ■ as a disease-specific IVD for use in clinical laboratories (EDL 4, Section II.b); ■ using an immunoassay format; ■ using serum and plasma as specimen types; ■ to diagnose and monitor congenital adrenal hyperplasia (CAH) outside of the neonatal period. SAGE IVD also recommended including a note to the EDL table stating that the test is not appropriate for screening.

Details of submission from 2022

Background

Disease condition and impact on patients Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a potentially life-threatening congenital disorder with significant mortality/morbidity if not promptly diagnosed, with treatment initiated at birth. Presentations vary from neonatal salt wasting (with atypical genitalia in girls) to failure to thrive. The disease is characterized by impaired cortisol and aldosterone production and by androgen excess. The disorder is challenging to diagnose and treat due to the complex direct and indirect effects of steroids on physiology. CAH is an autosomal recessive disorder. There is a nonclassical form of the disease which is milder and may form part of the etiology of the hirsutism polycystic ovary spectrum of disorders. While 17-OHP estimation can be diagnostic in the classical form, it is part of the investigative pathway for the nonclassical form. This application is confined to the classical form of CAH. Does the test meet a medical need? Determining blood levels of 17-OHP is required to diagnose and to monitor treatment of CAH. 17-OHP is also useful for newborn screening for CAH. However, because of the high false-positive rate of immunoassay methods in the neonatal period, a second-tier test by liquid chromatography-tandem mass spectrometry is recommended (1). How the test is used Blood spot testing can be used as part of a newborn screening programme. Ideally, neonates should not be tested before 48 hours of age due to cross-reacting substances. The test is also used to monitor CAH treatment and for follow-up.

Public health relevance

Prevalence For the classical form of CAH, analysis of data from almost 6.5 million newborns screened in different populations worldwide has demonstrated an overall incidence of 1:15 000 live births. The prevalence in specific populations has been reported to be 1:300 in the Yupik Eskimos of Alaska, 1:5000 in Saudi Arabia, 1:10 000–1:16 000 in Europe and North America, 1:21 000 in Japan and 1:23 000 in New Zealand (1). Socioeconomic impact Not provided

WHO or other clinical guidelines relevant to the test

Readers may refer to the Endocrine Society’s clinical practice guideline (2) for full details on recommendations.

Evidence for diagnostic accuracy

Not provided.

Evidence for clinical usefulness and impact

Not provided.

Evidence for economic impact and/or cost–effectiveness

Not provided.

Ethical issues, equity and human rights issues

The prevalence of CAH varies, being particularly high in certain Jewish populations in North America. Interpreting 17-OHP test results requires expertise. This is an inherent inequity where that expertise is not readily available. Lack of early diagnosis leads to increased morbidity and mortality of affected individuals. No specific ethical issues were identified.
1. Nimkarn S, Gangishetti PK, Yau M, New MI. 21-Hydroxylase-deficient congenital adrenal hyperplasia. 2002 Feb 26 [Updated 2016 Feb 4]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW et al., editors. GeneReviews [website]. Seattle (WA): University of Washington; 1993–2023 (https://www.ncbi.nlm.nih.gov/books/NBK1171/, accessed 5 April 2023). 2. Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(11):4043–88 (https://doi.org/10.1210/jc.2018- 01865, accessed 1 August 2023).