A 2-day-old infant is evaluated in the newborn nursery. The patient was born at term via spontaneous vaginal delivery to a 30-year-old woman. The pregnancy and delivery were uncomplicated. The mother had regular prenatal care, and her only medication was a daily prenatal vitamin. Family history is unremarkable. The patient's length at birth was at the 10th percentile. Weight and head circumference were at the 25th percentile. On initial examination after delivery, the patient was found to have ambiguous genitalia. The infant has been breastfeeding and has had appropriate urine and stool output. Examination shows an alert newborn with normal tone. The abdomen is soft with no palpable masses. Genitourinary examination reveals severe curvature of an underdeveloped phallus. The urethral meatus is at the base of the structure, flanked by labioscrotal folds; the gonads are not palpable. Examination of the mother shows no acne or hirsutism. Laboratory results are as follows: Which of the following is the most likely diagnosis in this patient?

Question

A 2-day-old infant is evaluated in the newborn nursery.  The patient was born at term via spontaneous vaginal delivery to a 30-year-old woman.  The pregnancy and delivery were uncomplicated.  The mother had regular prenatal care, and her only medication was a daily prenatal vitamin.  Family history is unremarkable.  The patient's length at birth was at the 10th percentile.  Weight and head circumference were at the 25th percentile.  On initial examination after delivery, the patient was found to have ambiguous genitalia.  The infant has been breastfeeding and has had appropriate urine and stool output.  Examination shows an alert newborn with normal tone.  The abdomen is soft with no palpable masses.  Genitourinary examination reveals severe curvature of an underdeveloped phallus.  The urethral meatus is at the base of the structure, flanked by labioscrotal folds; the gonads are not palpable.  Examination of the mother shows no acne or hirsutism.  Laboratory results are as follows:  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec25c8_d65b_7e5e_bc81_57071c21100d_MD0003_00 This newborn with a 46,XX karyotype and ambiguous genitalia likely has congenital adrenal hyperplasia (CAH). The most common cause of CAH is 21-hydroxylase deficiency, which results in decreased cortisol and aldosterone and increased 17-hydroxyprogesterone (17-OHP), the normal substrate for 21-hydroxylase. 17-OHP is then converted to testosterone in peripheral tissues. This excess androgen production leads to virilization (eg, clitoromegaly/underdeveloped phallus, nonpalpable gonads) in genotypically female (46,XX) infants, as seen in this patient. 21-hydroxylase deficiency Although most patients with classic CAH develop salt wasting (due to deficient aldosterone), electrolyte abnormalities (ie, hyponatremia, hyperkalemia) do not occur until age 1-2 weeks; in the first few days of life, serum electrolytes are normal due to the presence of maternal adrenal hormones. Patients with suspected CAH require prompt treatment with glucocorticoids and mineralocorticoids to avoid a potentially fatal adrenal crisis (eg, hypotension, dehydration, vomiting). (Choice A) 5-Alpha reductase deficiency causes defective conversion of testosterone to dihydrotestosterone and classically presents in genotypically male (46,XY) newborns with female or undervirilized external genitalia. In addition, the testosterone level is normal. (Choice B) Androgen insensitivity syndrome is due to a defect in the androgen receptor and presents in genotypically male (46,XY) newborns with undervirilized, ambiguous, or female external genitalia. This infant has a 46,XX karyotype. (Choice D) Placental aromatase deficiency prevents the conversion of placental androgens into estrogens. Androgen excess causes virilization of the female fetus. The mother is also typically virilized, which is not seen in this patient's mother, due to the transplacental transfer of androgens. (Choice E) Sertoli-Leydig cell tumors produce androgens (eg, 17-OHP, testosterone) and cause virilization in female patients; however, presentation is typically in early adulthood, not the newborn period. Educational objective: Classic congenital adrenal hyperplasia occurs due to 21-hydroxylase deficiency, which leads to the buildup of 17-hydroxyprogesterone and testosterone. Genotypically female newborns (46,XX) have virilized genitalia (eg, underdeveloped phallus) and nonpalpable gonads. Electrolyte abnormalities do not develop until age 1-2 weeks. References: Gender identity and sexual function in 46,XX patients with congenital adrenal hyperplasia raised as males. (http://www.ncbi.nlm.nih.gov/pubmed/30291599) An unexpected diagnosis in children with male phenotype and bilateral nonpalpable gonad: congenital adrenal hyperplasia with female genotype. (http://www.ncbi.nlm.nih.gov/pubmed/23624815)

A 2-Day-Old Infant Is Evaluated in the Newborn Nursery