sign in sign up
<<
Home , Gynaecology, Hermaphrodite, Intersex

Arch Dis Child: first published as 10.1136/adc.59.12.1191 on 1 December 1984. Downloaded from

Archives of Disease in Childhood, 1984, 59, 1191-1194

Personal practice problems

J DEWHURST AND D B GRANT Institute of and , Queen Charlotte's , and Hospital for Sick Children, Great Ormond Street, London

Paediatricians are familiar with the grief and anxiety XY/45 X mosaicism ('mixed gonadal dysgenesis'), which follow the birth of a child with a congenital or even a true with one within malformation. When this involves the genitalia and the abdomen. Absence of a palpable gonad suggests there is doubt about the true of the child, sorrow that the patient is a virilised (female is accompanied by embarrassment and dismay, pseudohermaphrodite), when the most likely di- leading to questions which cannot be ignored but agnosis is congenital adrenal hyperplasia. In this which may be difficult to answer. We believe that it condition the external genitalia may occasionally be is important for parents in this situation to be told almost completely masculinised and the only clue to that urgent investigation will be carried out to define the diagnosis may lie in the apparent bilateral their baby's problem, and that they are left in no of an otherwise normal boy. to an doubt that it will be possible make appropriate copyright. assignment of . The temptation to give a Investigation 'provisional' opinion must be avoided and in some cases it will be necessary to ask the local Registrar of Laboratory investigation of patients with intersex Births and Deaths for permission to defer registra- disorders has been reviewed in several recent tion until the more appropriate sex for the child has publications' 2 and will only be discussed briefly. been decided. With few exceptions, we believe that full chromo- some analysis is needed in children with ambiguous Initial assessment genitalia: while examination of a buccal smear for

nuclear chromatin can give a rapid result, the http://adc.bmj.com/ In general, two different types of genital malforma- findings may be misleading, particularly in patients tion are possible. In one, the appearance is of with abnormal sex patterns such as 45 extreme underdevelopment of otherwise normal X/46 XY mosaicism. male genitalia, with but no . If congenital adrenal hyperplasia seems the most Fetal gonadotrophin deficiency, other forms of likely diagnosis, estimation of plasma 17a- hypopituitarism, 'rudimentary testes', and Klinefel- hydroxyprogesterone and 11-deoxycortisol have ter's syndrome are the best recognised causes of this greatly facilitated the diagnosis of the 21- type of anomaly. In the other variety, the genitalia hydroxylase and 11-hydroxylase types of the dis- on September 25, 2021 by guest. Protected may show a pattern which is intermediate between order and have largely replaced analysis of urinary the normal male and female appearances, and it is steroids. not clear whether the patient is a boy with severe In patients with bilateral and a 46 XY hypospadias or a with cliteromegaly and fusion , investigation of plasma testosterone, of the labial folds. In these patients the presence or , and precursors be- absence of palpable gonads is an important physical fore and after stimulation with human chorionic sign. Bilateral inguinal gonads suggest that the gonadotrophin (1000 IU) given daily for three days patient is a poorly virilised male (male pseudo- will help to decide whether the patient has a defect hermaphrodite), or possibly a hermaphrodite with of testosterone (or dihydrotestosterone) synthesis, ovotestes. The presence of a unilateral gonad or whether testosterone production is normal and suggests several possibilities, including for example the basic problem is one of impaired sensitivity of a male pseudohermaphrodite, a patient with a testis the genital tissues to androgen. This latter type of and a contralateral dysgenetic gonad as a result of 46 case still poses one of the greatest challenges in 1191 Arch Dis Child: first published as 10.1136/adc.59.12.1191 on 1 December 1984. Downloaded from

1192 Dewhurst and Grant paediatric . While it is now possible to intersex disorders are associated with in determine whether the impaired response is related adult life although a few true have to an abnormality of the androgen binding receptors been reported as fertile.3 Thirdly, the views of the in cultures of genital skin, as yet these parents on the most appropriate sex for their child methods do not allow a clear prediction of the must be taken into account. The race and cultural degree of genital development which will take place background of the family may be very important, at the time of . We sometimes give such especially when they are from where men patients a brief course of low doses of depo- occupy much more prestigious positions than testosterone, for example 25 to 50 mg for a total of women. three injections given at four week intervals, to try A newborn female child with congenital adrenal to determine the likely extent of development at hyperplasia or induced masculinisation puberty. Unfortunately, the degree of enlargement will almost always be brought up in the female role, of the phallus in response to treatment is often regardless of the degree of masculinisation, which difficult to assess accurately, particularly as notice- can be corrected surgically. The extent to which able is usually present. A therapeutic trial ambiguous genitalia can be made into functioning of testosterone may be more successful in patients male organs is an important and often more difficult with micropenis, many of whom respond well with consideration in other cases; if this cannot be done good growth of the phallus. with any reasonable hope of success, the female role Radiographic investigation using contrast media should be chosen since it is always possible to to visualise the or may be of value, achieve this by surgical correction. particularly in patients who are likely to be raised as and who may require at a later Presentation in later childhood or at puberty date. In some patients or with In some instances, the presence of an intersex gonadal biopsy is indicated: this is particularly the disorder will not become apparent until later child- in a case in those with asymmetric gonadal development hood. For example, sup-copyright. or patients who show a discrepancy between the posedly cryptorchid boy may bring to light the clinical findings and the karyotype-for example, no presence of congenital adrenal hyperplasia in a palpable gonads in a patient with a 46 XY karyotype severely masculinised girl, or perhaps more com- or bilateral gonads in a patient with a 46 XX monly, virilisation at adolescence in an otherwise karyotype. In the former the biopsy may show the normal girl may occur as a result of undiagnosed presence of gonadal dysplasia; in the latter, testicu- male . lar and ovarian tissue indicating true hermaphrodit- In this situation, assignment of gender is con- ism. In general, laparotomy and gonadal biopsy are cerned with the suitability of the external genitalia

not indicated in girls with congenital adrenal hyper- for life in the in which the patient is http://adc.bmj.com/ plasia or in patients with bilateral gonads and a 46 already living and the orientation of the patient to XY karyotype. that role. If, as is usually the case, the external genitalia are appropriate to the gender in which the Assessment of gender in the newborn patient has been living and is well adjusted, this role would be maintained and underscored by any There are three important factors to be taken into surgical or hormone treatment which might be consideration when deciding the more appropriate required. The most difficult cases are those in which gender for an intersex patient. Firstly, the anatomy the patient, although well adjusted to the male role, on September 25, 2021 by guest. Protected of the genitalia must be assessed to define the ease has poor external genital development which might or difficulty of the surgical procedures which will be make sexual life as a male unsuccessful. One is faced needed to construct functional male or female with the very difficult decision whether to leave such external genitalia. Secondly, the pattern of pubertal a patient in the gender to which he is adjusted, but change which can be expected at the time of in which he cannot perform sexually, or to re- adolescence must be considered; will there be register in the opposite role and risk hopeless spontaneous virilisation or feminisation, and will psychological confusion. such changes be fairly complete or will treatment with or oestrogens be needed? Repro- Surgical management ductive potential is only an important consideration in girls with congenital adrenal hyperplasia or Mention must be made of the different surgical hormone-induced female pseudohermaphroditism procedures which may be necessary, with particular who are potentially fertile; most of the other reference to their timing. Arch Dis Child: first published as 10.1136/adc.59.12.1191 on 1 December 1984. Downloaded from

Intersex problems 1193 In a girl with congenital adrenal hyperplasia two rearing-should be removed; if the male role has procedures may be necessary, reduction in size of been chosen, will also be required. In the phallus and enlargement of the constricted either role external genital may be neces- vaginal introitus. Our preference is for reduction of sary. the during early infancy, and surgery can be performed in the neonatal period as soon as the Management at puberty congenital adrenal hyperplasia has been controlled. The advantage of this timing is that it allows the In congenital adrenal hyperplasia, close control of child to be discharged home without any visible sign the disorder will permit the development of secon- of masculinisation. dary and , Techniques exist for removing the corpora caver- although menarche often occurs a year or two later nosa yet retaining the sensitive glands,4 and good than usual. Fertility in these patients is probably results are usually obtained. Enlargement of the somewhat reduced, but many have had normal vaginal introitus is often a more difficult procedure and given birth to normal infants, and is better left until later, usually until after usually by . puberty. In the rare circumstance of an older girl Intersex patients who have had their gonads with congenital adrenal hyperplasia being brought removed require hormone replacement treatment at up as a boy and being well adjusted to that role, the usual time of puberty. In a patient growing up as hysterectomy and should be per- a female who has a and who can be expected formed before puberty to permit continued life as a to have menstrual bleeding, it is our practice to give male. At a later date testosterone treatment can be ethinyl oestradiol 10 to 20 [ig daily for three weeks in given, and testicular prostheses inserted. four. When withdrawal bleeding occurs a pro- A genetic male or with a gestogen can be given in the form of who is being raised as a girl will require 5 mg between days 12 and 21, in addition to the gonadectomy because of the increased risk of oestrogen. This regimen generally gives good secon- malignancy. The risk of this happening at some time dary sexual development and regular withdrawal copyright. in a frankly dysgenetic gonad may be of the order of periods. When the uterus is absent, the hormone 30%,5 while in the well formed gonads of patients replacement treatment can be continuous, and it is with androgen insensitivity the risk might be of the doubtful if a needs to be used. order of 5%.6 7 In patients who are raised as girls To achieve masculinisation in patients brought up but who show some genital masculinisation, it is our as boys, we use injections of depo-testosterone, practice to remove the testes during childhood to initially at a dose of 100 mg every six to eight weeks eliminate the risk of further masculinisation at and subsequently at a dose of 250 mg every three to puberty. In androgen insensitive patients who show six weeks. Some patients, however, show a poor no masculinisation and in whom spontaneous femi- response to this treatment, particularly those with http://adc.bmj.com/ nisation can be expected at puberty, orchidectomy tissue can be carried out when development is insensitivity to androgens. complete. In some 46 XY patients raised as girls construc- Family guidance tion of a vagina may be required but this is usually best deferred until adolescence or later. Most parents are at a loss as to how they can best A male intersex patient who is being brought up as explain the nature of the medical condition to their a boy will require surgical correction of his hypospa- child without implying that 'she really is a boy' or on September 25, 2021 by guest. Protected dias and associated chordee. Most urologists would that 'he started off as a girl'. We usually suggest that aim to complete surgery by the age of 3 to 4 years. the patient is told that the '' or 'testes' had to Orchidpexy is very often also required. In patients be removed because they were unhealthy or were with 46 XY or 45 X mosaicism any obviously producing 'the wrong balance of ', that dysgenetic gonadal tissue should be removed be- hormone treatment will be needed to bring on the cause of the high risk of malignancy. Macroscopi- correct changes of puberty, and that fertility is not cally normal testes are placed in the possible. In patients with male pseudohermaphro- whenever possible as they usually produce some ditism raised as girls it is also necessary to explain spontaneous virilisation at the time of puberty. that they iwere 'born without a uterus' and that Because of the risk of , however, they may menstruation will not occur. While these explana- be best removed when adolescence is complete. tions are probably adequate, at the time of adolesc- In a true hermaphrodite the inappropriate ence it is likely that at least some of these patients gonad-testis or , depending on the sex of will ultimately guess the true nature of their condi- Arch Dis Child: first published as 10.1136/adc.59.12.1191 on 1 December 1984. Downloaded from

1194 Dewhurst and Grant

tion and may welcome a chance to discuss it frankly 3 Kim MH, Gumpel JA, Graff P. in a true hermaphro- with their , or even their parents. dite. Obstet Gynecol 1978;53:405-25. 4 Dewhurst CJ. Practical pediatric and adolescent gynecology. May we end with a reassuring anecdote? One of New York: Marcel Dekker, 1980:40-7. us (JD) treated a masculinised girl who was changed 5 Fathalla MF, Rashad MN, Kerr MG. The relationship between from male to female at the age of 4 years.8 She was ovarian tumours and intersex states with special reference to the told that an error in assignment had been made and disgerminoma and arrhenoblastoma. Journal of Obstetrics and Gynaecology of the British Commonwealth 1966;73:812. she had always been female. Over 20 years later, 6 Jones HW, Scott WW. Hermaphroditism, genital anomalies and now a happily married , she presented again related endocrine disorders. 2nd ed. Baltimore: Williams and because of difficulty in conceiving. She is now Wilkins, 1971. pregnant. 7 Dewhurst CJ, Ferreira HP, Gillett PG. Gonadal malignancy in XY . Journal of Obstetrics and Gynaecology of the British Commonwealth 1971;78:1077. References 8 Dewhurst CJ, Gordon RR. Change of sex. Lancet 1963;ii:1213. Simpson JL. Disorders of . New York: Academic Press, 1976. 2 Josso N. The intersex child: pediatric and adolescent endocrin- Correspondence to Dr D B Grant, Hospital for Sick Children, ology. Vol 8. Basel: Karger, 1981. Great Ormond Street, London WC1N 1EH. copyright. http://adc.bmj.com/ on September 25, 2021 by guest. Protected