Measurements of 17α-hydroxyprogesterone appear to be of value in populations at high risk for nonclassic late-onset 21-hydroxylase deficiency. In the white population, the gene occurs in only about 1 in 1,000 individuals, but it occurs in 1 in 27 Ashkenazi Jews, 1 in 40 Hispanics, 1 in 50 Yugoslavs, and 1 in 300 Italians (84). The incidence is increased among Eskimos and French Canadians. Alternatively, screening might be restricted to hirsute teenagers presenting with the more “typical” features of nonclassic 21-hydroxylase deficiency, including severe hirsutism beginning at puberty, “ﬂattening” of the breasts (i.e., defeminization), shorter
Figure 29.22 Left: A 19-year-old girl with secondary amenorrhea and severe acne and hirsutism beginning at the normal age of puberty. Stimulatory testing with corticotropin documented nonclassic 21-hydroxylase deficiency. Flattening of the breasts is apparent. She was shorter than her one sister and her mother.
Figure 29.23 Right: Newborn girl with 46,XX karyotype and genital ambiguity. There is obvious clitoral hypertrophy, paired frenula, so-called scrotalization of the labia, and a common urogenital sinus (shown by the probe). She had 21-hydroxylase deficiency. (From Rebar RW. Normal and abnormal sexual differentiation and pubertal development. In: Moore TR, Reiter RC, Rebar RW, et al., eds. Gynecology and obstetrics: a longitudinal approach. New York: Churchill Livingstone, 1993:97–133, with permission.) stature than other family members, and increased DHEAS levels (between 5,000 and 7,000 ng/mL). Women with a strong family history of hirsutism or hypertension might be screened (49) (Fig. 29.22).
Basal Levels of 17α-Hydroxyprogesterone Basal levels of 17α-hydroxyprogesterone higher than 800 ng/dL are virtually diagnostic of CAH. Levels between 300 and 800 ng/dL require stimulatory testing with corticotropin to distinguish between PCOS and CAH. To complicate the situation even further, nonclassic 21-hydroxylase deficiency may occur even when basal levels of 17α-hydroxyprogesterone are below 300 ng/dL, thus requiring stimulatory testing in those cases.
Cosyntropin Stimulation Test The most commonly used stimulatory test involves measurement of 17α-hydroxyprogesterone 30 minutes after administration of a bolus of 0.25 mg of synthetic cosyntropin (Cortrosyn) (96). In normal women, this value seldom exceeds 400 ng/dL. Patients with classic 21-hydroxylase deficiency achieve peak levels of 3,000 ng/dL or higher. Patients with nonclassic 21-hydroxylase deficiency commonly achieve levels of 1,500 ng/dL or more. Heterozygous carriers achieve peak levels up to about 1,000 ng/dL. In hirsute women with hypertension, 11-deoxycortisol levels can be determined during the test. If both 11-deoxycortisol and 17α-hydroxyprogesterone levels are increased, the rare 11-hydroxylase deficiency is present. Only measurements of several steroid precursors after corticotropin stimulation can identify individuals with nonclassic forms of 3β-HSD deficiency.