From the Guidelines
Congenital adrenal hyperplasia (CAH) is evaluated using several key tests, with the primary diagnostic test being the measurement of 17-hydroxyprogesterone (17-OHP) levels in the blood, as recommended by recent guidelines 1. The evaluation of CAH involves a combination of laboratory tests and physical examinations.
- The measurement of 17-OHP levels is crucial, as it is elevated in the most common form of CAH (21-hydroxylase deficiency) 1.
- An ACTH stimulation test may be performed to measure multiple adrenal steroid levels before and after stimulation, including 17-OHP, cortisol, androstenedione, and 11-deoxycortisol.
- Additional tests include electrolyte measurements to check for salt-wasting (sodium, potassium, and aldosterone levels), plasma renin activity, and genetic testing to identify specific mutations in the CYP21A2 gene or other genes associated with less common forms of CAH.
- In newborns with ambiguous genitalia, karyotyping may be performed to determine genetic sex, as failure to diagnose CAH can result in serious harm, including shock, hyponatremia, and hyperkalemia 1.
- Prenatal diagnosis is possible through chorionic villus sampling or amniocentesis if there is a family history of CAH. These tests help determine the type and severity of CAH, which guides appropriate treatment with glucocorticoids, mineralocorticoids, and sometimes salt supplementation, ultimately improving morbidity, mortality, and quality of life for patients with CAH. It is essential to note that the evaluation and treatment of CAH should be guided by the most recent and highest-quality evidence, and the measurement of 17-OHP levels is the primary diagnostic test, as supported by the latest study 1.
From the Research
Diagnostic Tests for Congenital Adrenal Hyperplasia (CAH)
The diagnosis of CAH is made by clinical, biochemical, and molecular genetic evaluation 2. The following tests are used to evaluate for CAH:
- 17-hydroxyprogesterone (17-OHP) level: measured early in the morning, a level above 1000 ng/dL is indicative of 21-hydroxylase deficiency (21-OHD) 2
- Adrenocorticotropic hormone (ACTH) stimulation test: performed in cases with borderline 17-OHP levels (200-1000 ng/dL) to confirm the diagnosis of 21-OHD 2
- Genotyping: performed in cases with CAH to determine the genetic mutation and to identify carriers among family members 2
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS): a sensitive and specific method for measuring 17-OHP levels in serum 3
- Immunoassay: a commonly used method for measuring 17-OHP levels, but may not be as sensitive or specific as LC-MS/MS 3, 4
Interpretation of Test Results
The interpretation of test results is crucial in diagnosing and managing CAH. For example:
- A basal 17-OHP level of 6.0 nmol/L is not a sensitive predictive marker for diagnosing nonclassical CAH, and an ACTH stimulation test may be necessary to confirm the diagnosis 4
- A 4-hour profile of 17-OHP levels may not be useful in predicting hyperandrogenemia in children with salt-wasting CAH 5
- Suppressed levels of 17-OHP do not always indicate overtreatment, and reference intervals for 17-OHP may vary depending on the time of day and other factors 5