Luciane Carneiro de Carvalho1, Vinicius Nahime Brito1, Regina Matsunaga Martin1, Aline Machado Zamboni1, Larissa Garcia Gomes1, Marlene Inácio1, Livia Mara Mermejo2, Fernanda Coeli-Lacchini2, Virginia Ribeiro Teixeira3, Fabrícia Torres Gonçalves4, Alexandre José Faria Carrilho5, Kenny Yelena Del Toro Camargo6, Gabriela Paula Finkielstain7, Giselle Fernandes Taboada8, Elaine Maria Frade Costa1, Sorahia Domenice1, Berenice Bilharinho Mendonca9. 1. Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular/LIM 42, Disciplina de Endocrinologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil. 2. Divisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto-USP, São Paulo, Brasil. 3. Divisão de Endocrinologia, Universidade Federal do Ceará, Fortaleza, Ceará, Brasil. 4. Divisão de Endocrinologia do Hospital das Clínicas da Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brasil. 5. Divisão de Endocrinologia, Universidade Estadual de Londrina, Londrina, Paraná, Brasil. 6. Unidad Médica Villa Country, Barranquilla, Colombia. 7. División de Endocrinología, Centro de Investigaciones Endocrinológicas, Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, Argentina. 8. Divisão de Endocrinologia, Universidade Federal Fluminense, Niterói, RJ, Brasil. 9. Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular/LIM 42, Disciplina de Endocrinologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil. Electronic address: beremen@usp.br.
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, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% 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 68.7% and ovarian macrocysts in 62.5% 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.I223Nfs*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 hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.
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, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% 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 68.7% and ovarian macrocysts in 62.5% 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.I223Nfs*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 hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.