Ambiguous Genitalia in the Newborn

Abstract

Ambiguous genitalia in the newborn need immediate and rational management. This complex situation requires a strategy of clinical, hormonal, genetic, molecular, and radiographic investigation to determine the etiology of the intersex state and orient the therapeutic approach. Physical examination is key to diagnosis. Careful palpation to locate gonads at the genital folds or in the inguinal region provides the first element for diagnostic orientation. If gonads are absent, a diagnosis of female pseudohermaphroditism seems advisable; if gonads are palpated, a diagnosis of male pseudohermaphroditism is more appropriate. Karyotyping is systematic while polymerase chain reaction (PCR) analysis of the SRY gene provides information about the presence of a Y chromosome within 1 day. Hormonal investigation should be based on clinical and genetic orientation. Substantially elevated plasma 17-OH progesterone will confirm the diagnosis of congenital adrenal hyperplasia due to deficiency in 21-hydroxylase. Testicular stimulation with human chorionic gonadotropin (hCG) will determine the functional value of testicular tissue. Exploration of the genitourinary axis is principally carried out by ultrasound and genitography. By the end of these investigations, the medical team should be able to give a precise diagnosis. Female pseudohermaphroditism may be due to excess fetal androgens (congenital adrenal hyperplasia), increased androgen production of maternal origin, or placental androgen excess. In male pseudohermaphroditism, if testosterone rises normally after hCG stimulation, androgen resistance is indicated. If it does not rise after this test, either testicular dysgenesis or disturbance in testosterone biosynthesis may be responsible. The assignment of sex for rearing must be guided by the etiology of the genital malformation, the anatomic condition, and family considerations. In cases of female pseudohermaphroditism, the newborn should always be declared to be of female sex at birth. In cases of male pseudohermaphroditism, great care should be taken in the declaration of male sex: the potential for reconstructive surgery and the pubertal "programmed" response of the external genitalia to endogenous and exogenous testosterone are determinant. Management of ambiguous genitalia in the newborn requires an entire multidisciplinary team in every step of the diagnostic procedure, the choice of sex assignment, and the treatment strategy.

Fluorescent in situ hybridization for sex chromosome determination before and after fertilization in mice

“…In human medicine, FISH identification of the X and Y chromosome has been employed to determine the genetic sex of babies that have ambiguous genitalia [40][41][42]. Various mutant mice strains and domestic animals may also have ambiguous genitalia at birth [43] and provide an additional application for, XY FISH analysis.…”

The role of the pediatrician in the management of children with genital ambiguities

“…Os exames hormonais e o cariótipo devem ser realizados em serviços especializados, assim como a avaliação por imagem de útero, gônadas, próstata e seio urogenital, que é necessária, porém nem sempre conclusiva 1,2,5,6,15,19,20 . Os procedimentos mais utilizados são ultra-sonografia em associação com genitografia (ou uretrocistografia miccional retró-grada) e, menos freqüentemente, tomografia computadorizada ou ressonância nuclear magnética da região pélvica 22,23 .…”

As novas definições e classificações dos estados intersexuais: o que o Consenso de Chicago contribui para o estado da arte?

“…Com a descoberta dos cromossomos, alguns autores passaram a definir PHM como ambigüidade genital em presença de um cariótipo 46,XY e PHF como ambigüidade genital com cariótipo 46,XX, mantendo-se a anatomia gonadal como base para o diagnóstico de HV. Revisões recentes sobre o assunto adotam a classificação com base no tipo de gônada e na constituição cromossômica (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”