Review Question - QID 105402

This adolescent female with a family history of classic congenital adrenal hyperplasia (CAH), virilization, hirsutism, acne, short stature, and possible late-onset of menses likely has nonclassic (aka late-onset) CAH, caused by a 21-hydroxylase deficiency.

CAH is an autosomal recessive disorder that has several different forms. The most severe, classic form presents in newborn females with salt-wasting and ambiguous genitalia. Milder, nonclassic forms can present anytime from childhood to adulthood with the signs and symptoms found in this case. While 21-hydroxylase deficiency causes most forms of the disorder, other enzyme deficiencies, including 11-beta-hydroxylase, can also cause the disorder (Illustration A).

Deaton et al. review CAH and point out that although the severe form of this disorder is rare, the milder forms have a prevalence of up to 1 in 100 women in the US. Women with infertility, hirsutism, and oligomenorrhea often have CAH but may not be correctly diagnosed. Diagnosis is made using an adrenal corticotropic hormone challenge, which will reveal elevated levels of 17-hydroxyprogesterone, with different cut-offs for classic and nonclassic CAH.

Hans et al. review treatment for CAH. Although glucocorticoid treatment has proven life saving, particularly for the classic form, achieving physiologic levels of corticosteroids is difficult and only occurs in about 1/3 of patients. Common complications, often due to inadequate treatment, include obesity, osteoporosis, and infertility.

Illustration A shows the effects of 21-hydroxylase deficiency on the cortisol and aldosterone pathways. The bolded products (progesterone and 17-hydroxyprogesterone) build up as a result of the enzymatic deficiency.

Incorrect answers:
Answer 2: The hirsutism associated with polycystic ovarian syndrome (PCOS) is slow-onset, rather than rapid as in this case. Other distinguishing characteristics include obesity, insulin resistance, and irregular menses.
Answer 3: Hypothyroidism may present with some signs of hyperandrogenism, but symptoms usually include fatigue, weight gain, and amenorrhea.
Answer 4: Hyperprolactinemia may present with some signs of hyperandrogenism, but symptoms usually include galactorrhea, amenorrhea, and infertility.
Answer 5: Like CAH, an androgen-secreting neoplasm can cause rapid-onset hirsutism, but usually is found in individuals > 30 years old and often presents with a pelvic mass.