Diagnóstico de 408 casos de ambiguidade genital acompanhados por uma única equipe interdisciplinar durante 23 anos

Orientador: Gil Guerra JúniorDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Objetivo: verificar a frequência dos diagnósticos, a idade e a definição do sexo dos casos de Distúrbio da Diferenciação do Sexo (DDS) com ambiguidade genital. Casuística e métodos: Foram incluídos todos os casos atendidos entre janeiro de 1989 e dezembro de 2011 num mesmo serviço de avaliação clínica e laboratorial. O critério de definição de ambiguidade genital foi o proposto pelo Consenso de Chicago de 2006. Foram analisados os cariótipos, diagnósticos, a idade na primeira consulta, o peso ao nascimento e a definição do sexo de criação. Resultados: Foram 408 casos de DDS com ambiguidade genital, sendo 250 (61,3%) com cariótipo 46,XY, 124 (30,4%) 46,XX e 34 (8,3%) com aberração de cromossomos sexuais. Dos 408 casos, 189 (46,3%) foram DDS 46,XY testicular, 105 (25,7%) DDS 46,XX ovariano, 95 (23,3%) distúrbio da determinação gonadal (DDG) e 19 (4,7%) por malformações genitourinárias complexas. Dentre os DDS 46,XY testicular, destacaram-se os casos de insensibilidade androgênica, deficiência de 5?-redutase tipo 2 e hipogonadismo hipogonadotrófico. Dentre os DDS 46,XX ovariano, a principal causa foi a hiperplasia adrenal congênita por deficiência da 21-hidroxilase forma perdedora de sal. Nestes dois grupos foram observados vários casos de DDS com outras malformações associadas. Dentre os DDG, os mais frequentes foram as disgenesias gonadais parciais XY, as disgenesias gonadais mistas e os DDS ovotesticular. O peso de nascimento abaixo de 2.500 g foi observado em 42 casos de DDS 46,XY testicular. A idade média ao diagnóstico foi de 31,7 meses, sendo menor no grupo de DDS 46,XX ovariano. O sexo de criação final foi masculino em 238 casos e feminino em 170. Conclusões: Nesta ampla casuística de DDS com ambiguidade genital acompanhados por uma única equipe durante 23 anos, o cariótipo 46,XY foi o mais observado, porém a hiperplasia adrenal congênita foi a etiologia isolada mais frequente. As malformações associadas foram frequentes em todos os grupos de DDS e o baixo peso ao nascimento esteve associado ao DDS 46,XY testicularAbstract: Objective: To verity the frequency of the diagnosis, age and sex definition of Disorder of Sex Development (DSD) with ambiguous genitalia cases. Methods: All cases followed between January 1989 and December 2011 with the same clinical and laboratory service were included. The genital ambiguity criteria was proposed by the Chicago Consensus of 2006. The karyotype, diagnosis, age on their first visit, birth weight and gender of rearing, were analysed. Results: There were 408 cases of DSD with genital ambiguity, 250 (61.3%) with 46,XY karyotype, 124 (30.4%) 46,XX and 34 (8.3%) with sex chromosomes aberration. Of the 408 cases, 189 (46.3%) were 46,XY testicular DSD, 105 (25.7%) 46,XX ovarian DSD, 95 (23.3%) disorder of gonadal development (DGD) and 19 (4,7%) due to complex genitourinary malformations. Among the 46,XY testicular DSD, the cases of androgen insensitivity, 5?-reductase type 2 deficiency and hypogonadotropic hypogonadism were highlighted. Among the 46,XX ovarian DSD, the main cause was the congenital adrenal hyperplasia due 21-hydroxylase deficiency in salt wasting form. In both groups, several cases of DSD with other associated malformations were observed. Among the DGD, the most frequent were the 46,XY partial gonadal dysgenesis, mixed gonadal dysgenesis, and the ovotesticular DSD. Birth weight less than 2,500 g was observed in 42 cases of 46,XY testicular DSD. The average age at diagnosis was 31.7 months, and lower in the 46,XX ovarian DSD group. The final social sex was male in 238 cases and female in 170. Conclusions: In this large sample of DSD with ambiguous genitalia accompanied by a single team for 23 years, 46,XY karyotype was the most observed, however congenital adrenal hyperplasia was the most frequently isolated etiology. The associated malformations were common in all DSD groups and low birth weight was associated with the 46,XY testicular DSDMestradoSaude da Criança e do AdolescenteMestra em Ciência

Leydig and Sertoli cell function in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion : a case-control study

BACKGROUND: Because normal male sexual differentiation is more complex than normal female sexual differentiation, there are more cases of disorders of sex development (DSDs) with 46,XY karyotype that have unclear etiology. However, Leydig and Sertoli cell markers are rarely used in distinguishing such individuals. OBJECTIVES: To evaluate the function of Leydig and Sertoli cells in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion. STUDY DESIGN AND SETTING: Case-control study with 77 patients, including eight with partial androgen insensitivity syndrome, eight with 5α-reductase deficiency type 2 (5ARD2) and 19 with idiopathic 46,XY DSD, and 42 healthy controls, from the Interdisciplinary Study Group for Sex Determination and Differentiation (GIEDDS), at the State University of Campinas (UNICAMP), Campinas, Brazil. METHODS: Baseline levels of gonadotropins, anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), testosterone and dihydrotestosterone in cases, and AMH, inhibin B, and INSL3 levels in controls, were assessed. RESULTS: There was no significant difference in age between cases and controls (P = 0.595). AMH and inhibin B levels were significantly lower in cases than in controls (P = 0.031 and P < 0.001, respectively). INSL3 levels were significantly higher in cases than in controls (P = 0.003). Inhibin B levels were lower in 5ARD2 patients (P = 0.045) and idiopathic patients (P = 0.001), in separate comparisons with the controls. CONCLUSION: According to our findings, we can speculate that inhibin B levels may be used to differentiate among DSD cases

408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

Objective. To evaluate diagnosis, age of referral, karyotype, and sex of rearing of cases with disorders of sex development (DSD) with ambiguous genitalia. Methods. Retrospective study during 23 years at outpatient clinic of a referral center. Results. There were 408 cases; 250 (61.3%) were 46,XY and 124 (30.4%) 46,XX and 34 (8.3%) had sex chromosomes abnormalities. 189 (46.3%) had 46,XY testicular DSD, 105 (25.7%) 46,XX ovarian DSD, 95 (23.3%) disorders of gonadal development (DGD), and 19 (4.7%) complex malformations. The main etiology of 46,XX ovarian DSD was salt-wasting 21-hydroxylase deficiency. In 46,XX and 46,XY groups, other malformations were observed. In the DGD group, 46,XY partial gonadal dysgenesis, mixed gonadal dysgenesis, and ovotesticular DSD were more frequent. Low birth weight was observed in 42 cases of idiopathic 46,XY testicular DSD. The average age at diagnosis was 31.7 months. The final sex of rearing was male in 238 cases and female in 170. Only 6.6% (27 cases) needed sex reassignment. Conclusions. In this large DSD sample with ambiguous genitalia, the 46,XY karyotype was the most frequent; in turn, congenital adrenal hyperplasia was the most frequent etiology. Malformations associated with DSD were common in all groups and low birth weight was associated with idiopathic 46,XY testicular DSD