Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects

Author(s):Show less -

de Carvalho, Luciane Carneiro ^[1] ; Brito, Vinicius Nahime ^[1] ; Martin, Regina Matsunaga ^[1] ; Zamboni, Aline Machado ^[1] ; Gomes, Larissa Garcia ^[1] ; Inacio, Marlene ^[1] ; Mermejo, Livia Mara ^[2] ; Coeli-Lacchini, Fernanda ^[2] ; Teixeira, Virginia Ribeiro ^[3] ; Goncalves, Fabricia Torres ^[4] ; Faria Carrilho, Alexandre Jose ^[5] ; Del Toro Camargo, Kenny Yelena ^[6] ; Finkielstain, Gabriela Paula ^[7] ; Taboada, Giselle Fernandes ^[8] ; Frade Costa, Elaine Maria ^[1] ; Domenice, Sorahia ^[1] ; Mendonca, Berenice Bilharinho ^[1]

Affiliation

^[1] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM 42, Disciplina Endocrinol, Hosp Clin, Fac Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Div Endocrinol, Dept Clin Med, Fac Med Ribeirao Preto, Sao Paulo - Brazil

^[3] Univ Fed Ceara, Div Endocrinol, Fortaleza, Ceara - Brazil

^[4] Univ Fed Uberlandia, Hosp Clin, Div Endocrinol, Av Engenheiro Dinz 1178, CP 593, BR-38400 Uberlandia, MG - Brazil

^[5] Univ Estadual Londrina, Div Endocrinol, Londrina, Parana - Brazil

^[6] Unidad Med Villa Country, Barranquilla - Colombia

^[7] Hosp Ninos Dr Ricardo Gutierrez, Ctr Invest Endocrinol, Div Endocrinol, Buenos Aires, DF - Argentina

^[8] Univ Fed Fluminense, Div Endocrinol, Niteroi, RJ - Brazil

• Document type: Journal article
• Source: Fertility and Sterility; v. 105, n. 6, p. 1612-1619, JUN 2016.
• Web of Science Citations: 7

Abstract

Objective: To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. Design: Retrospective study. Setting: Tertiary care center. Patient(s): Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. Intervention(s): None. Main Outcome Measure(s): Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. Result(s): Seventy-one percent of patients presented with primary amenorrhea, 500/0 had no breast development, and pubic hair was absent or sparse in all patients; 880/o had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.70/0 and ovarian macrocysts in 62.50/0 of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/ p.1223Nfs{*}10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. Conclusion (s): Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogoriadisiri point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques. (Fertil Steil(R) 2016;105:1612-9. (C) 2016 by American Society for Reproductive Medicine.) (AU)

• FAPESP's process: 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine
• Grantee: Berenice Bilharinho de Mendonça
• Support Opportunities: Research Projects - Thematic Grants