Management framework paradigms for disorders of sex development

Until 2005, questions regarding medical treatment and diagnostic information on Disorders of Sex Development (DSD) were not systematically discussed with both the patients and their families; however, the way these patients are currently treated have been changing with time. Interventional changes in the clinical-psychotherapeutic-surgical areas of DSD determine not only different medical recommendations but also help to place the patient and the family into the decisional process of therapy. We must consider two paradigmatic periods that have influenced and transformed the clinical management framework of patients with DSD: a) The "Money era" (1955), which emphasized the role of the gonads as the diagnostic criterion, having the environment as determinant of the sex identity; and b) The Chicago Consensus (2005) phase, in which the role of genetics and molecular biology was critical for an early identification, as well as in building a proper sex identity, emphasizing ethical questions and the "stigma culture". In addition, recent data have focused on the importance of interdisciplinarity and statements on questions concerning Human Rights as key factors in treatment decision making. Despite each of these management models being able to determine specific directions and recommendations regarding the clinical handling of these patients, we verify that a composite of these several models is the clinical routine nowadays. In the present paper, we discuss these several paradigms, and pinpoint clinical differences and their unfolding regarding management of DSD patients and their families.

Multifunctional role of steroidogenic factor 1 and disorders of sex development / Papel multifuncional do fator esteroidogênico 1 e as doenças do desenvolvimento sexual

Disorders of sex development (DSD) involve several conditions that result from abnormalities during gonadal determination and differentiation. Some of these disorders may manifest at birth by ambiguous genitalia; others are diagnosed only at puberty, by the delayed onset of secondary sexual characteristics. Sex determination and differentiation in humans are processes that involve the interaction of several genes such as WT1, NR5A1, NR0B1, SOX9, among others, in the testicular pathway, and WNT4, DAX1, FOXL2 and RSPO1, in the ovarian pathway. One of the major proteins in mammalian gonadal differentiation is the steroidogenic nuclear receptor factor 1 (SF1). This review will cover some of the most recent data on SF1 functional roles and findings related to mutations in its coding gene, NR5A1.

Os distúrbios do desenvolvimento sexual (DDS) envolvem várias condições que resultam de anormalidades que podem acontecer tanto na determinação como durante a diferenciação gonadal. Algumas dessas doenças podem se manifestar ao nascimento principalmente por genitália ambígua, outras são diagnosticadas apenas na puberdade por atraso no aparecimento de características sexuais secundárias. A determinação e a diferenciação do sexo em seres humanos são processos que envolvem interações entre vários genes nas vias testicular, tais como NR5A1, NR0B1, WT1, SOX9, entre outros, e ovariana, tais como WNT4, DAX1, FOXL2 e RSPO1. Uma das principais proteínas na diferenciação gonadal de mamíferos é o fator esteroidogênico e receptor nuclear 1 (SF1). Esta revisão cobrirá alguns dos dados mais recentes sobre os papéis funcionais de SF1 e as últimas descobertas relacionadas a mutações em seu gene, NR5A1.

As novas definições e classificações dos estados intersexuais: o que o Consenso de Chicago contribui para o estado da arte? / New definitions and classifications of the intersexual states: in which the Chicago Consensus has contributed to the state of the art?

As anomalias da diferenciação sexual têm-se constituído em um formidável desafio quanto ao diagnóstico e à conduta, colocando o paciente, os familiares e os profissionais da equipe de saúde na difícil situação de definir a melhor opção quanto ao gênero de criação. Uma terminologia confusa e estigmatizante tem sido adotada e, nesse sentido, o Consenso de Chicago propõe várias modificações no sentido de minimizar os desconfortos graças a uma terminologia que nem sempre auxilia na solução de problemas. Os autores fazem uma análise crítica da classificação sugerida pelo Consenso, levantando a questão de que, na nova classificação, também não se resolvem certos problemas terminológicos e continua a se criar algum grau de estigmatização. Em primeiro lugar, a sugestão de se incluir o cariótipo no nome da doença supõe, erroneamente, que os pacientes não tenham conhecimento do que significa ser 46,XY ou 46,XX. Uma criança criada no sexo feminino com uma anomalia da diferenciação sexual (ADS) 46,XY não vai entender porque está no sexo feminino se seu cariótipo é "masculino". A substituição do termo hermafroditismo verdadeiro por ADS ovotesticular está longe de resolver o problema de estigmatização causado por "hermafroditismo". O termo ovotesticular é claramente entendido como uma fusão entre ovário e testículo e não será aceito com "naturalidade". Se, por um lado, é muito satisfatório que a questão da nomenclatura seja discutida, por outro lado devemos escolher termos alternativos que sejam realmente neutros e não tragam, em si, a conotação de um sexo que pode não condizer com o escolhido para aquele paciente em particular. Um ponto em que todos concordamos é que a substituição de intersexo por anomalia da diferenciação sexual (ADS) ou, disorder of sex development (DSD), na língua inglesa, cai muito melhor e não dá a conotação de um "sexo intermediário" como o nome antigo proporcionava.

Disorders of sex development have posed a tremendous challenge not only in the diagnosis but also in the treatment, placing the patient, the family members, and the health team in the difficult task of attributing the best sex of rearing for that specific patient. A confusing and stigmatizing nomenclature has been employed and the Chicago Consensus tried to minimize the discomfort with modifications of the current terminology. The authors perform a critical analysis of the Consensus, raising the question that the new terminology does not solve the problems and persist being stigmatizing to the patient and to the family. First of all, the inclusion of the karyotype in the name of the disease holds the false premise that the patients do not know the meaning of a 46,XY or a 46,XX karyotype. A child raised in the female sex will not understand that her disease holds a "male" karyotype in its name (46,XY DSD). The substitution of ovotesticular DSD for true hermaphroditism maintains the stigma of the name since ovotesticular is easily perceived as ovarian and testicular tissues. If, on one hand, the recognition of using terms like intersex and hermaphroditism are stigmatizing, on the other hand, we need terms that are really neutral to not create problems of sexual identification. One point in which there is consensus is that the change of the term "intersex" for "disorder of sex development" is highly desirable and eliminates the idea of an "intermediate sex".

Male Pseudohermaphroditism

An unusual case of a 40-year-old infertile male is presented. On examination he had cryptorchidism with other normal secondary sexual characters. Ultrasonography and computerized tomography raised the suspicion of tumour in the right abdominal testis. On exploration, a uterus with cervix, fallopian tubes and abdominal testes were detected. This was confirmed histopathologically. Chromosomal analysis revealed 46XY

Ambiguous genitalia in children

Management of patients with ambiguous genitalia is a challenging problem. This has very rightly been described as a psychosocial emergency. Our social circumstances and diagnostic deficiencies pose problems in the management of such children. One cannot diagnose and manage such cases without basic knowledge of events of determination of sex and factors controlling gondal development. It is important to have an early diagnosis, proper gender assignment and necessary treatment for better results. 1. To evaluate children presenting with ambiguous genitalia. 2. To see the proportion of various types of pseudohermaphrodism. 3. To highlight various management problems. 4. To discuss the results of management. DESIGN: Prospective study. SETTING: Pediatric surgery department of Mayo Hospital, Lahore, Allied Hospital, Faisalabad and Bahawalpur Victoria Hospital, Bahawalpur. PERIOD: 1990 to 1998. PATIENTS AND METHODS: Ambiguous genitalia total number 48. There were 38[79%] cases of male pseudohermaphroditism, 6[13%] cases of female pseudohermaphroditisrn, 2[4%] cases had mixed gondal dysgnesis and 1[2%] had true hermaphroditism. In one[2%] case there was neurofibromatosis involving vulva and clitoris

Desórdenes de la diferenciación sexual, y pubertad retardada

Ante una persona cuya edad cronológica no parece corresponder a su maduracion sexual o en la que se encuentran caracteres sexuales incongruentes con el sexo en el que fue clasificado al nacimiento, es indispensable proceder a estudio completo y cuidadoso, que incluya valoración de las hormonas gonadales y de los esteroides suprarenales, para identificar y tratar a tiempo los posibles desórdenes de la diferenciación sexual (virilización en las niñas o feminización en los varones) o retardo de la pubertad

Mixed gonadal dysgenesis and dysgenetic male pseudohermaphroditism--a critical analysis.

A 10 year prospective study of 14 patients with mixed gonadal dysgenesis (MGD) and six patients with dysgenetic male pseudohermaphroditism (DMP) is reported. All of them had internal mullerian structures, along with unilateral or bilateral dysgenetic testes, ambiguous external genitalia. Twelve had been brought up as male, nine of whom had a unilateral descended testis. Eight had been reared as females, as they had bilaterally undescended gonads, and ambiguous genitalia. Clinical examination, retrograde genito-urethrography and cytogenetic studies suggested the diagnosis in 16 patients, while four were diagnosed on inguino-abdominal exploration for undescended testis. This report delineates more clearly the clinical profile of these orders. All the patients reared as male were assigned the male gender following abdominal gonadectomy, retention of scrotal testis and male genitoplasty. The eight patients who were reared as females underwent bilateral salpingo-gonadectomy and female genitoplasty. This management differs from the usual recommendation that all such children should be reared as females. Ten patients (50%) had maternal history of previous abortion/stillbirth, or drug intake in the first trimester of pregnancy suggesting a role of these factors in the etiology. All cases of DMP had a 46,XY karyotype, while eight of 14 cases of MGD had mosaicism with 45X/46,XY cell lines in blood or gonadal cultures. The clinicopathological features of patients of MGD and DMP were similar. It is suggested that these two disorders represent different spectra of the same disorder. A unifying concept of etiopathogenesis is proposed.

Genitografia: técnicas e classificaçäo segundo Shopfner / Genitography: technics and shopfner's classification

A genitografia é o método mais adequado para a determinaçäo de presença ou ausência da vagina e de sua relaçäo com a uretra, o que é um dado de suma importância para a escolha do tratamento que propicie ao paciente com genitália ambígua uma vida sexual prática aceitável. Shopfner (1964) descreveu uma classificaçäo, baseada na anatomia, que pode ser demonstrada por genitografia. Apresentamos 13 genitografias realizadas com as técnicas de flushing, múltiplos cateteres e fase miccional de uretrocistografia, as quais exemplificam todos os tipos de classificaçäo de Shopfner. A técnica da fase miccional de uretrocistografia como complementaçäo das técnicas de flushing ou de cateter foi a que mais bem permitiu a realizaçäo de genitografias