From the Guidelines
Congenital adrenal hyperplasia (CAH) should be diagnosed through a combination of clinical evaluation, laboratory tests, and genetic analysis, with a focus on screening newborns for 21-hydroxylase deficiency using a blood test that measures 17-hydroxyprogesterone (17-OHP) levels, as elevated 17-OHP strongly suggests CAH 1. The diagnostic process for CAH involves several key steps, including:
- Screening newborns for 21-hydroxylase deficiency, the most common form of CAH, using a blood test that measures 17-OHP levels
- Performing comprehensive adrenal hormone panels to measure cortisol, aldosterone, androstenedione, testosterone, and ACTH levels
- Conducting an ACTH stimulation test to evaluate adrenal function by measuring hormone levels before and after ACTH administration
- Genetic testing for mutations in the CYP21A2 gene (for 21-hydroxylase deficiency) or other relevant genes to confirm the diagnosis and identify the specific CAH variant Clinical signs that may prompt investigation for CAH include:
- Ambiguous genitalia in female newborns
- Salt-wasting crisis in infants
- Precocious puberty in children
- Fertility issues and hirsutism in adults Early diagnosis of CAH is crucial, as prompt treatment with glucocorticoids (like hydrocortisone) and sometimes mineralocorticoids (like fludrocortisone) can prevent life-threatening adrenal crises and manage symptoms effectively 1. In cases where bilateral adrenal incidentalomas are present, screening for CAH with 17-hydroxyprogesterone should be considered, especially if the masses are likely to be metastasis from a known other malignancy, and adrenal function should be assessed 1.
From the Research
Diagnosis of Congenital Adrenal Hyperplasia
Diagnosis of congenital adrenal hyperplasia (CAH) can be achieved through various methods, including:
- Newborn screening programs that measure 17-hydroxyprogesterone (17OHP) levels 2
- Clinical presentations, such as premature adrenarche, growth acceleration, hirsutism, and irregular menses in children and adolescents 3
- Quantitative measurement of low levels of cortisol and other adrenal steroids, as well as increased levels of steroids proximal to the blocked step 4
- Observation of clinical syndromes reflecting distinct hormonal patterns 4
Laboratory Tests
Laboratory tests used to diagnose CAH include:
- 17OHP levels, which are elevated in CAH due to 21-hydroxylase deficiency 3, 2
- 21-deoxycortisol levels, which are a more specific marker for 21OHD than 17OHP 2
- Cortisol levels, which are decreased in CAH 4, 5
- Androstenedione levels, which are elevated in CAH 5
- Deoxycorticosterone (DOC) levels, which are extremely high in 17α-hydroxylase deficiency 6
Newborn Screening
Newborn screening programs have been implemented to detect CAH early, using 17OHP levels as a marker 2. However, this method has limitations, such as false positives and elevated 17OHP levels in premature infants or infants with physiologic stress from unrelated diseases 2. Replacement of 17OHP with 21-deoxycortisol as the analyte of choice for studies of 21OHD has been suggested 2.
Genetic Testing
Genetic testing can also be used to diagnose CAH, by identifying specific mutations in the genes responsible for the enzyme deficiencies 4, 6. For example, a homozygous missense mutation in the CYP17A1 gene has been identified as the cause of 17α-hydroxylase deficiency in two sisters 6.