Background: 46,XY patients with SF-1 mutations have sex reversal or ambiguous genitalia (with or adrenal insufficiency) due to dysgenetic testis. In most cases, a severe defect in testosterone (T) production has been found. We described here 3 cases showing the variability in T production.
Results: Case 1: A was seen at the age of 17 years for primary amenorrhea. Tanner stage was B2PH3. External genitalia were normal. FSH was 55 IU/l, LH 17 IU/l, inhibin B <10 pg/ml, AMH <0.1 ng/ml, testosterone 0.22 ng/ml, E2 <10 pg/ml, and DHEA-S 2.4 mg/l. Pelvic ultrasound showed a small uterus, and gonads with no follicles. Karyotype was 46,XY, and a p.Arg362X NR5A1 mutation was found. Case 2: B was born at term with microphallus (L 2.5 cm), penoscrotal hypospadias, and scrotum with two palpable gonads. Karyotype was 46,XY. T at d13 was 4.5 nmol/l, increasing to 11.8 nmol/l upon hCG stimulation. FSH was 2.9 IU/l, LH 1.6 IU/l. He was raised as a boy. At the age of 14 years, testis length was 3.5 cm, and phallus length 5.5 cm. T was 21 nmol/l, FSH 19 IU/l, LH 10 mIU/l, INHB 65 pg/ml, and AMH 1.7 ng/ml. A p.Val83Met NR5A1 mutation was found. Case 3: C was born at term with DSD (genital tubercle 10 mm, fused genital swellings with two palpable gonads, and one orifice). Karyotype was 46,XY, T 0.35 nmol/l increasing to 1.5 nmol/l upon hCG stimulation, AMH 7.2 ng/ml, and at 0.5 months FSH was 5 mIU/L, LH 0.7 mIU/l. C was raised as a girl and gonadectomy and feminizing genitoplasty were performed at 2 months. At the age of 11 years, ACTH was 191 pg/ml and cortisol 1.3 μg/dl, indicating adrenal insufficiency. A p.C422X NR5A1 mutation was found.
Conclusion: SF1 mutations showed large phenotypic and hormonal variability.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology