THU622 Spontaneous Pregnancy In Isolated 17,20-lyase Deficiency
Authors: de Oliveira Julia Martins , Santos Sobral Paulo Marcelo , Genari Celso Monteiro , Auchus Richard J , Kater Claudio Elias , Costa Barbosa Flávia Amanda 
Published: October 2023

Abstract
Disclosure: J.M. Oliveira: None. P.M. Sobral: None. C.M. Genari: None. R.J. Auchus: None. C.E. Kater: None. F.C. Barbosa: None.
Introduction: 17-Hidroxylase/17,20-lyase deficiency (17OHD) is Brazil's second most common form of congenital adrenal hyperplasia and results from pathogenic variants in the CYP17A1 gene. The typical manifestations of 17OHD are a female phenotype, sexual infantilism, arterial hypertension, and hypergonadotrophic hypogonadism. In contrast, isolated 17,20-lyase deficiency (ILD) is due to pathogenic variants of genes in the catalytic system of the 17,20-lyase, which include: CYP17A1, POR, or CYB5A. In 46XX ILD patients, primary amenorrhea, absence of pubarche, and irregular menses have been reported whereas in 46XY ILD patients, hypospadias, micropenis, and bifid scrotum have been described. Both ILD and 17OHD are associated with infertility. Assisted reproductive technology may rarely result in pregnancy. In this challenging scenario, we present the first known case of spontaneous pregnancy in a patient with ILD. Clinical case: A 16y female was referred to the Endocrinology Department due to the absence of pubarche. She developed thelarche at 9y and menarche at 11y, with oligomenorrhea (6-month-interval cycles) ever since. She had normal blood pressure, external vulvovaginal genitalia, and a complete absence of pubarche and axillary hair. ILD was suspected. Laboratory: undetectable levels of testosterone, androstenedione, and DHEAS. Estradiol: 25.9 (12.5-166.0)pg/mL, 17OHP: 290 (20-130)ng/dL, Progesterone: 111 (3.1-15.2)ng/dL, FSH: 4.2 (3.5-12.5)mUI/mL, LH: 9.5 (2.4-12.6)mUI/mL (all reference intervals are for follicular phase). Pre/post-ACTH stimulation test cortisol: 10/14.5 (7-25/≥18) mcg/dL, corticosterone: 2131/12342 (95-1500/-) ng/dL, 17OHP: 149/159 (up to 110/63.2-296.4) ng/dL, DOC: 10/34 (up to 25/-) ng/dL, respectively. Pelvic USG showed right and left ovaries of 11.0 and 14.9cm3, respectively. CYP17A1 sequencing identified the homozygous pathogenic variant R347H at exon 6, confirming ILD. The patient was oriented to use glucocorticoids during stressful situations and oral contraceptives continuously. She lost follow-up for one year and, at 19y, returned with 20 weeks of gestation. Prenatal was uneventful and cesarean delivery was performed at 41 weeks, giving birth to a healthy boy. Conclusions: There are very few case reports of pregnancy among 46XX patients with ILD. In all cases, fertility treatments were necessary. This is, to the best of our knowledge, the first spontaneous gestation in a patient with an established diagnosis. The Homozygous R347H variant, associated with excessive gonadotrophic stimulation, might be linked to the intermittent and residual enzymatic 17OHase (65%) and 17,20-lyase activity (&lt;5%). The resulting estrogenic gonadal effect (even in the lower range) may have been sufficient for folliculogenesis, ovulation, and the development of an adequate uterine environment for fertilization and spontaneous gestation.
Presentation: Thursday, June 15, 2023