From the Guidelines
Testing for congenital adrenal hyperplasia (CAH) should start with a 17-hydroxyprogesterone (17-OHP) blood test, which is the primary screening test for the most common form of CAH (21-hydroxylase deficiency) 1. This test is crucial as it helps in the early diagnosis of CAH, which can cause significant morbidity and mortality if left untreated. The 17-OHP test should be performed in the morning when levels are highest. Additional hormone measurements, such as ACTH, cortisol, androstenedione, testosterone, and renin levels, may be necessary to assess the severity and type of enzyme deficiency. An ACTH stimulation test can also be performed to evaluate adrenal function by administering synthetic ACTH (cosyntropin 250 mcg IV) and measuring cortisol and 17-OHP levels at 0,30, and 60 minutes. Genetic testing for mutations in the CYP21A2 gene can confirm 21-hydroxylase deficiency, while testing for other genes (CYP11B1, CYP17A1, HSD3B2) may be needed for rarer forms of CAH. Some studies also suggest that patients with abnormal endocrine testing or in whom there is a persistent concern for underlying endocrine disorder should be evaluated by an endocrinologist 1. Prenatal diagnosis is possible through chorionic villus sampling or amniocentesis if there is a family history. Early diagnosis is crucial as CAH can cause salt-wasting crises in newborns and virilization in females, requiring prompt treatment with glucocorticoids and sometimes mineralocorticoids. It's worth noting that other conditions, such as primary aldosteronism, obstructive sleep apnea, and pheochromocytoma/paraganglioma, can also cause hypertension and should be considered in the differential diagnosis 1. However, the primary focus should be on testing for CAH using the 17-OHP blood test and other relevant hormone measurements. Key points to consider when testing for CAH include:
- Performing the 17-OHP test in the morning when levels are highest
- Using additional hormone measurements to assess the severity and type of enzyme deficiency
- Considering genetic testing for mutations in the CYP21A2 gene
- Evaluating patients with abnormal endocrine testing by an endocrinologist
- Considering prenatal diagnosis if there is a family history.
From the Research
Testing for Congenital Adrenal Hyperplasia
To test for congenital adrenal hyperplasia (CAH), the following methods can be used:
- Newborn screening using 17-hydroxyprogesterone (17-OHP) levels, which is mandated throughout the US 2
- Heel prick blood samples collected between 72 and 96 hours postbirth and analyzed using enzyme-linked immunosorbent assay (ELISA) 3
- ACTH stimulation test to show 17-OHP concentrations above the normal response, typically >30 nmol/L 4
- Confirmatory testing for adrenocorticotropic hormone (ACTH) and cortisol levels 3
Factors Affecting 17-OHP Levels
Several factors can affect 17-OHP levels, including:
- Birth weight, with lower birth weights resulting in higher 17-OHP levels 2, 5
- Gestational age, with preterm infants having higher 17-OHP levels 5
- Sampling time, with 17-OHP levels decreasing with increasing sampling time 5
- Critical illness, which can cause falsely elevated 17-OHP results 2
Establishing Cutoff Values
Establishing region-specific 17-OHP cutoff values is crucial for improving screening accuracy 3