A 17-year-old girl is brought to the clinic due to irregular menses. Menarche was at age 12 and her cycles since then have been irregular, often with multiple months between menstrual periods. The patient also has had an increase in hair growth along her chest and face. Temperature is 37.3 C (99.1 F), blood pressure is 110/70 mm Hg, and pulse is 80/min. There are dark, terminal hairs above the patient's upper lip and nodulocystic acne across her forehead. Cardiopulmonary examination is normal. Sexual maturity rating (Tanner stage) is 5. Ultrasound examination of the pelvis reveals a normal uterus and ovaries. Electrolytes are normal; other laboratory results are as follows: Which of the following enzyme reaction steps is most likely to be disrupted in this patient?

Question

A 17-year-old girl is brought to the clinic due to irregular menses.  Menarche was at age 12 and her cycles since then have been irregular, often with multiple months between menstrual periods.  The patient also has had an increase in hair growth along her chest and face.  Temperature is 37.3 C (99.1 F), blood pressure is 110/70 mm Hg, and pulse is 80/min.  There are dark, terminal hairs above the patient's upper lip and nodulocystic acne across her forehead.  Cardiopulmonary examination is normal.  Sexual maturity rating (Tanner stage) is 5.  Ultrasound examination of the pelvis reveals a normal uterus and ovaries.  Electrolytes are normal; other laboratory results are as follows:  Which of the following enzyme reaction steps is most likely to be disrupted in this patient?

Quizplus · Accepted Answer

11ec160b_3ab2_56bf_9249_674f2a871485_MD0001_00 This patient's laboratory findings are consistent with 21-hydroxylase deficiency, the most common cause of congenital adrenal hyperplasia (CAH). The 21-hydroxylase enzyme is responsible for conversion of progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone (17-OHP) to 11-deoxycortisol. Enzyme deficiency causes the buildup of 17-OHP, which is then shunted toward androgen production. Deficiency of 21-hydroxylase can result in varying clinical phenotypes depending on the amount of residual enzyme available. This patient's presentation in adolescence with menstrual irregularities and signs of androgen excess (ie, hirsutism, nodulocystic acne) is consistent with the mildest form, nonclassic (late-onset) CAH. Other common findings of nonclassic CAH include premature pubarche (ie, early appearance of pubic/axillary hair) and accelerated growth and bone age in school-aged children. Because 21-hydroxylase is not completely absent in nonclassic CAH, sufficient mineralocorticoids are produced to avoid the salt wasting (ie, hypotension, hyperkalemia) seen in neonates with severe classic CAH. Laboratory studies in all forms of 21-hydroxylase deficiency reveal elevated 17-OHP and testosterone levels. (Choices A and B) Patients with 11 beta-hydroxylase deficiency have impaired conversion of 11-deoxycorticosterone to corticosterone and 11-deoxycortisol to cortisol. In addition to hyperandrogenism, patients have hypertension and hypokalemia (not seen here) due to increased 11-deoxycorticosterone (a weak mineralocorticoid). (Choice C) Conversion of pregnenolone to 17-hydroxypregnenolone is impaired with 17 alpha-hydroxylase deficiency. Patients have hypertension and hypokalemia due to increased mineralocorticoid synthesis and amenorrhea and absent secondary sexual characteristics due to absent sex hormone production. In addition, 17-OHP and testosterone are decreased with this disorder. (Choice E) Aromatase converts testosterone to estradiol. Due to lack of estrogens, aromatase deficiency results in primary amenorrhea, absent breast development, and virilized genitalia (eg, clitoromegaly) in girls. Educational objective: Nonclassic congenital adrenal hyperplasia is due to mild deficiency of 21-hydroxylase, an enzyme that converts progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol. In adolescent girls, it presents with signs of hyperandrogenism (eg, hirsutism, acne, menstrual irregularities) as well as increased 17-hydroxyprogesterone and testosterone levels.

A 17-Year-Old Girl Is Brought to the Clinic Due to Irregular