Advice on the Management of Ambiguous Genitalia to a Young Endocrinologist From Experienced Clinicians

Jean D. Wilson, M.D.; Marco A. Rivarola, M.D.; Berenice B. Mendonca, M.D., Ph.D.; Garry L. Warne, A.M., M.B.B.S., F.R.A.C.P.; Nathalie Josso, M.D., Ph.D.; Stenvert L.S. Drop, M.D., Ph.D.; Melvin M. Grumbach, M.D.

Disclosures

Semin Reprod Med. 2012;30(5):339-350. 

In This Article

Marco A. Rivarola, M.D.

I have chosen to discuss some personal opinions on a controversial issue; that is, on how to communicate to the family (parents, child, and relatives depending on each case), the views of the multidisciplinary health care team about diagnosis and interventions in pediatric patients with DSD. In this difficult subject, disagreement is very common.

Age of DSD Patient

Schematically, three life periods can be distinguished in dealing with these patients before adulthood: (1) the perinatal period, including prenatal diagnosis and the first few postnatal months of life, when parents (or foster parents) take first-line responsibility in defining what can be best for the child, (2) between 1 and 10 years of age, when gender reassignment is best avoided, and (3) between 11 years of age and late adolescence, when patients, after having lived within one sex for several years, decide to change or not. These age periods are approximate.

The Perinatal Period

The members of a multidisciplinary team need to reach some degree of agreement in the ethical principles and recommendations to be followed for the management of children with DSD.[3] Any decision, such as sex of rearing, surgical interventions to correct genital ambiguity, or gonadectomy, requires the participation and informed consent of the parents. Obviously, the patient cannot participate but it is generally believed that postponing decisions is not in the best interest of the child. In any case, the informed consent of the parents (or occasionally the foster parent) is required. The infant (or newborn) has the right to be benefited by the best decision taken in her or his behalf by the parents recognizing that there is a potential, unresolved conflict of interest: the right of the parents to decide about their children versus the right of the newborn as a future adult.

Prenatal sex discordances might be suspected when, occasionally, as a result of chorionic villus sampling, abnormal sex chromosome constitution or a karyotype:phenotype (assessed by ultrasound) discordance is detected. Likewise, analysis of cell-free fetal DNA in maternal plasma via detection of the SRY gene[4,5] might be discordant with an ultrasound genital image. In such instances, appropriate counseling can be provided by an experienced member of a DSD team.

When a baby is born with ambiguous genitalia, the following is the guidance to a young endocrinologist:

  1. If you work in a peripheral institution, proceed as follows: (a) perform a careful physical examination and register all genital findings, and take a careful family history; (b) screen for adrenal insufficiency and be prepared for possible emergency intervention, (c) tell parents that studies are needed to determine the cause of the abnormal genitalia, and refer them to an institution with a DSD Multidisciplinary Health Care Team with experience in the management of these newborns, and (d) do not assign a gender before appropriate studies are performed.

  2. If you work in a referral institution with such a DSD team, the newborn should be referred to the team for study and management of the problem.

The conformation of the DSD team usually varies depending on institutions. The Multidisciplinary Health Care Team at Hospital de Pediatria Garrahan of Buenos Aires (DSD Team) includes a pediatric endocrinologist, a pediatric surgeon specialized in gynecology, a pediatric urologist, a psychologist, a pediatrician, a specialist in legal medicine with experience in gender reassignment, and support from the Hormonal Laboratory, Molecular Biology Laboratory, Cytogenetics Service, and Imaging Service.

Functioning of the DSD Medical Team

The coordinator of a DSD multidisciplinary team has traditionally been a specialist in genetics, pediatrics, surgery, or endocrinology. However, the specific individual should reflect the person with the best experience, motivation, team work, and managerial skills on the subject, depending on local circumstances.[1] In our center, discussions with family members and communicating their views to the team are the responsibility of the pediatric endocrinologist, who is the informing professional. It has to be kept in mind that the medical team can (and should) recommend decisions, but parents (or older patients depending on age) decide, after receiving appropriate information.

General recommendations on gender assignment in a newborn are based on the following:

  • Etiological diagnosis and, if available, molecular diagnosis. Diagnosis of the type of DSD is helpful because published (and personal) experience on the outcomes of different forms of DSD can be taken into account.

  • External genitalia, including estimation of their future functional possibilities.

  • Internal urogenital tract and fertility potential.

  • Surgery is a delicate issue. Benefits of postponing interventions or waiting for personal decisions should be balanced against the psychological stress of carrying genital malformations or opposite-gender gonads during childhood. In this issue, the parents' decision is decisive. In any event, a conservative stand is usually appropriate.

  • Paternal acceptance.

  • Psychological evaluation of parents and future support from family members and social environment.

  • Potential perinatal sex hormone effects on the central nervous system. Even though there is strong experimental evidence in animals for these effects, this factor is of weak practical help. Whereas general recommendations can be outlined, decisions have to be individualized. Recommendations have to be extensively discussed inside the team and with the two parents. Sometimes, decisions are relatively easy, but they can be very difficult. Occasionally, all options are poor, including not assigning a gender, and the presumptive lesser evil is chosen. In these situations, it is recognized that patients may not be satisfied when they reach adulthood. Criticisms from patient advocacy groups have been helpful in reconsidering some of previous medical practices. Mutual collaboration helps to improve decisions.

Between 2 and 8 Years of Age

Occasionally, the assigned sex is questioned sometime during prepuberty, such as when a gonad with the characteristic of a testis is palpated in the inguinal regions, in a girl. In most instances, no need for gender reassignment arises. In any event, this would be psychologically an extremely difficult and risky undertaking at these ages.

Between 11 Years of Age and Late Adolescence

Gender reassignment might rise during adolescence, from male to female or female to male. Examples are (1) a 46,XX subject with CAH raised as a boy and who has complete or almost complete virilization of external genitalia and precocious male-type puberty but presence of uterus, fallopian tubes, and ovaries; and (2) a subject with 46,XY androgen insensitivity syndrome with female breast development but presence of testes, or a 46,XY individual with testicular dysgenesis who has partially virilized at puberty, in these two instances raised as girls. A thorough psychological evaluation and complete disclosure of organic differentiation along with appropriate biological explanations are mandatory. This requires a lot of expertise from the DSD medical team, as well as a strong psychological and prolonged support for making a decision.

Information Management

Information management involves disclosure of information both from the DSD medical team to parents and patients and from child/family to the wider environment.[6] Obviously, the parents of newborn have to be informed initially, particularly when gender is not certain. Words should be selected carefully avoiding misunderstandings and offensive interpretations. Information has to be complete, but this is complex to implement. To be clear enough, it requires appropriate explanations. Difficult biological facts need to be given using a terminology that parents (later on patients) can understand. Both parents need to be present during disclosure. It is advisable, before starting, to ask parents what information have they already received and what they think (and wish) about their baby's sex. It is also important to frequently stop explanations to ask parents what they have understood so far, in their own words. Then, we can use these words to go on with the conversation. Moreover, understanding the social and cultural background of the family is crucial for a fruitful relationship between parents and doctors. However, it is sometimes difficult to coordinate (or avoid) disclosure of information to parents by different members of the team. Also parents listen to comments from multiple sources, inside and outside medical centers. Special efforts should be made by the informing professional to ensure appropriate understanding of the situation, including chromosomal constitution, gene function, heredity, gonadal development, as well as external and internal genitalia differentiation. Complete explanation of this complex information may require several sessions; therefore, a careful selection of priorities is necessary.

Follow-up

During follow-up, patients will go through all stages of growth and development (from infancy to adolescence and ultimately adulthood), and information has to be delivered appropriate for the educational and mental development. The medical team has to be permanently alert to new developments that might arise along many years and to give answers to questions that frequently have a high emotional impact.

Final Comment

Patients with DSD should receive long-term care provided by multidisciplinary teams in centers of excellence with ample experience in this clinical management. However, members of any team should be aware that errors could be made. Therefore, decisions should be carefully thought and discussed before final recommendations are made.

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