Diagnosis and Management of Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a condition of excess androgen production by the adrenal cortex as a result of deficient or decreased enzymatic activity in one of the precursors involved in corticosteroid production. CAH manifests in approximately 1 in 15,000 births.1 There are several types of CAH, depending on which enzyme production is lacking (Figure 1), and the mode of inheritance is autosomal recessive. The most common form of CAH is 21-hydroxylase deficiency (accounting for approximately 90%–95% of all CAH), which is attributable to a defect in the CYP21A2 gene on chromosome 6p21.3. The carrier rate in the general population is approximately 1:60. Higher carrier rates are seen in discrete populations such as Alaskan Yupik Eskimos and Ashkenazi Jews.1 Other forms of CAH include 11 -hydroxylase deficiency (5%–8% of all CAH with higher numbers in Moroccan Jews), 17 -hydroxylase and 17,20-lyase deficiencies (1% of all CAH and 5%–7% of CAH in Brazil), and 3 -hydroxysteroid dehydrogenase, p450 side chain, and P450 oxidoreductase deficiencies. This article focuses on 21-hydroxylase deficiency, given the overwhelming predominance of this defect in patients with CAH. Understanding this diagnosis is important for clinicians, as patients can present with a broad range of manifestations that can have significant implications to both gynecologic and obstetric practice. Because this is a confusing diagnosis, there is a gap between typical and ideal practices; the goal of this article is to address this gap. Classic CAH occurs when only 0% to 1% of enzymatic activity is present in the fetus in utero.2 Although the female internal genitalia are normally formed by the 10th week of gestation, the external genitalia are affected by excess adrenal androgen exposure. Varying degrees of female pseudohermaphroditism (fusion of labioscrotal folds and clitoral enlargement) develop depending on the timing of exposure, ranging from complete masculinization with early androgen exposure (10–12 weeks’ gestation) or isolated clitoral hypertrophy (18–20 weeks’ gestation).3 The clinician must suspect classic CAH when evaluating any infant born with genital ambiguity. In conjunction with virilization, salt-wasting can occur in some patients with CAH when aldosterone production is inadequate. These infants can present with electrolyte abnormalities and failure to thrive and should also be evaluated for CAH. This may be fatal within the first week of life if untreated. Nonclassic CAH is a milder form of CAH, which occurs when 20% to 50% of enzymatic activity is present.4 Symptoms Learning Objectives: After participating in this activity, the obstetrician/gynecologist should be better able to: 1. Appropriately screen and diagnose both classic and nonclassic congenital adrenal hyperplasia (CAH). 2. Medically manage patients with both classic and nonclassic CAH. 3. Identify a patient’s risk of offspring with CAH.