A female second born of unrelated parents, at fourth pregnancy, born by vaginal delivery at 39 weeks of gestational age, weight 3145 g (-0.45 SDS), length 50 cm (0.12 SDS), head circumference 33 cm (-0.82 SDS), presented with DSD. The mother affected by hypothyroidism and autoimmune hepatitis, during the whole pregnancy was treated with levothyroxine and prednisone at the dose of 5 mg/day. At birth mild ambiguous genitalia (Prader stages I-II) were noticed and the baby was admitted to neonatology department for clinical assessment.
Laboratory tests showed high levels of 17hydroxyprogesterone(510 ng/ml), ACTH (329 pg/ml) and testosterone (9 ng/ml). Ultrasound of the abdomen showed normal uterus and ovaries. After genetic counseling, karyotype, analysis for SRY and CYP21 genes were performed. The exams confirmed the diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency [655 I2 Splice (C>G) intron2; R356 W (exone 8)] in a newborn with a female karyotype of 46, XX. Cystourethrography has not be performed yet.
Therapy with hydrocortisone was started with subsequent reduction of 17hydroxyprogesterone, ACTH and testosterone levels. At 1 months of age she presented a salt-wasting crisis, so replacement therapy with fludrocortisone and sodium solution was added.
The baby was discharged at 5 weeks of age in good general condition and is followed up regularly in the pediatric endocrinology department.
In CAH deficient fetal cortisol production leads to overproduction of ACTH, stimulating the disordered fetal adrenal to produce excess androgens, virilizing female fetuses at 7-12 weeks gestation; however development of the ovaries, uterus and fallopian tubes remains normal.
Supraphysiological doses of exogenous steroids are required to supress androgen excess and it was shown that prenatal dexamethasone treatment of fetuses at risk of congenital adrenal hyperplasia can prevent virilization of a female fetus. This treatment has since been offered at the dose of 20 mcg/kg maternal body weight per day, to avoid the need for feminizing genital reconstructive surgery and the risk of complications, and remains controversial. However, this treatment has shown a success rates of 85%. The long-term effects of steroids in early pregnancy remain unclear, with potential detrimental effects on fetal programming, brain function and congenital anomalies.
In this case, although the baby has a severe form of salt-wasting CAH, at birth she has minimal virilization (Prader stages I-II). We hypothesize that maternal therapy with prednisone at low dose since the beginning of the gestation, partially prevented virilization of the child genitalia.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology