Diagnosis and differential diagnosis of congenital adrenal hyperplasia (CAH) always requires the measurement of several steroids. Patients with CAH due to steroid 21-hydroxylase gene (
CYP21A2)
mutations usually have very high levels of androstenedione, often 5- to 10-fold elevations. 17-hydroxyprogesterone (OHPG) levels are usually even higher, while cortisol levels are low or undetectable. All 3 analytes should be tested.
In the much less common CYP11A1 mutation, andostenedione levels are elevated to a similar extent as in CYP21A2 mutation, and cortisol is also low, but OHPG is only mildly, if at all, elevated.
In the also very rare 17-alpha-hydroxylase deficiency, androstenedione, all other androgen-precursors (17-alpha-hydroxypregnenolone, OHPG, dehydroepiandrosterone sulfate), androgens (testosterone, estrone, estradiol), and cortisol are low, while production of mineral corticoid and its precursors, in particular progesterone, 11-deoxycorticosterone, and 18-hydroxycorticosterone, are increased.
The goal of CAH treatment is normalization of cortisol levels and ideally also of sex-steroid levels. Traditionally, OHPG and urinary pregnanetriol or total ketosteroid excretion are measured to guide treatment, but these tests correlate only modestly with androgen levels. Therefore, androstenedione and testosterone should also be measured and used to guide treatment modifications. Normal prepubertal levels may be difficult to achieve, but if testosterone levels are within the reference range, androstenedione levels of up to 100 ng/dL are usually regarded as acceptable.