Postgrad Med J: first published as 10.1136/pgmj.43.496.117 on 1 February 1967. Downloaded from

Case reports 117

Formation of an artificial in a case of testicular feminization A. E. R. BUCKLE J. WATSON M.B.(Lond.), F.R.C.S., M.R.C.O.G. M.A., M.B.(Cantab.), F.R.C.S. Consultant, Department of Obstetrics and Consultant Plastic Surgeon Lewisham General Hospital, London, S.E.13

THE syndrome of testicular feminization is found oxosteroids 18-2 mg in 24 hr; urinary 17-hydroxy- in persons of female phenotype, which includes corticoids 23-9 mg in 24 hr; pituitary follicle- female external genitalia, who have primary stimulating hormone negative (less than 6 mouse amenorrhoea; the tend to be under- units); buccal smears showed no sex chromatin developed, the vagina ends blindly and the cervix present. Later analysis showed a chromosome is absent. Usually pubic and axillary hair is scanty number of 46 with normal XY complement. or absent after puberty and breast development is With an etablished diagnosis of testicular good. The internal genitals are absent or rudi- feminization syndrome, it was decided to attempt mentary and the gonads, which may be intra- plastic vaginal enlargement together with removal abdominal or in the inguinal canal, are testes of the gonads, because of the risk of malignant (Morris, 1953). The chromosomes appear normal with XY sex chomosomes. The condition is in- change (Morris, 1953). At the time that this patient herited, either in a sex-linked recessive or sex- was originally seen, four other cases of the testicu- limited dominant manner (Taillard & Prader, lar feminization syndrome (one with a teratoma of

1957). the intra-abdominal testis) were under intensive by copyright. Although the vagina may be of sufficient length biochemical investigation in the hospital and the to allow of coitus, this is not always the case. patient was therefore further investigated prior to Reports on the surgical correction of the in- surgery. adequate vagina are rare and we would like to report on the management of a patient with Further investigations testicular feminization who requested plastic en- Plasma 17-hydroxycorticoids: at the lower limit largement prior to . of the female range. Plasma 1 7-oxosteroids: upper limit of the Case report female range and more typical of levels found in The patient, aged 35 years, attended as an out- men. patient in May 1964. She gave a history of pri- Plasma testosterone levels: in the male range http://pmj.bmj.com/ mary amenorrhoea on account of which she had and definitely exceeding the range found in nor- sought advice at another hospital 12 years earlier. mal females. At that time she had been told that the uterus was Urinary oestrogen levels: at the upper limit of absent and that the vagina was very short; no the normal male range, below the average daily further investigation was carried out and, although amount excreted by a normal female during a surgical correction was mentioned, no arrange- complete cycle, but higher than in women with ments were made for this to be done. She was now primary amenorrhoea. intending marriage and sought advice regarding The effect of ACTH and HCG administration on October 2, 2021 by guest. Protected the possibility of operation to allow of normal on the daily excretion of oestradiol 17-,8, oestrone marital relations. The family history was negative. and oestriol and on plasma testosterone was esti- On examination the patient was tall (height mated before operation. 1-9 m), attractive, blonde-haired and of normal At the time of operation, blood was obtained female build (see Fig. 1). Pubic and axillary hair from the gonadal venous plexus for the estimation was absent, breast development normal and the of plasma testosterone levels. The latter level was external genitalia of female type, although the found to be some ten times higher than levels labia majora were underdeveloped. The vagina found in the peripheral plasma. The half-life of was short (2 cm) and blind ending. testosterone in the plasma was determined and found to be normal. The secretion rates of Investigations dehydroepiandrosterone and its sulphate were Haemoglobin 12 g / 100 ml; chest X-ray normal; found to be of male and not female pattern. Full serum cholesterol 235 mg/ 100 ml; urinary 17- details of these investigations, together with the Postgrad Med J: first published as 10.1136/pgmj.43.496.117 on 1 February 1967. Downloaded from

118 Case reports

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FIG. 1 results from the four other cases of the syndrome apex of the space. Haemostasis was obtained and mentioned above, have been published elsewhere the cavity sprayed with 'Polybactrin' antibiotic (Deshpande et al., 1965). spray. The graft-covered mould was inserted into

the space, the labia sutured over the mould and http://pmj.bmj.com/ Operation an in-dwelling catheter inserted. After induction of anaesthesia, a split-skin graft The patient was now positioned for laparotomy. was taken from the patient's right thigh. This graft The abdomen was opened through a Pfannenstiel was subsequently sutured to itself, raw surface incision and, on entering the peritoneal cavity, the outwards, over an acrylic resin mould, 15 cm in site of the vaginal mould was seen producing a length. A solid mould was chosen in this particular surface elevation of the peritoneum between instance rather than one constructed of rolled bladder and rectum. The absence of the uterus plastic sponge (the technique usually employed) and Fallopian tubes was confirmed, the gonad on on October 2, 2021 by guest. Protected because this was thought safer, for the vault of the the left side lying just caudal to the normal ovarian new vagina would be in apposition to the pelvic position and the gonad on the right lying at the peritoneum; there was thus a possible danger of level of the internal inguinal ring. Blood was escape of fragments of sponge into the peritoneal obtained from the venous plexus for testosterone cavity if the graft failed and the peritoneal layer estimation, bilateral gonadectomy performed and broke down. After the donor site had been the abdomen closed in layers. dressed, the patient was placed in the lithotomy Post-operatively, the patient was given prophy- position. lactic antibiotic cover for 14 days, bladder drain- The apex of the blind-ending vagina was incised age being continued for a similar period of time. transversely and the space between bladder and There was a rise in temperature on the 3rd post- rectum separated widely in both longitudinal and operative day, associated with slight purulent loss transverse directions. At the completion of the from the centre of the vaginal mould. The tem- dissection, the peritoneum could be seen at the perature soon subsided and, apart from bowel Postgrad Med J: first published as 10.1136/pgmj.43.496.117 on 1 February 1967. Downloaded from

-Case reports 119 distension, the patient remained well after opera- the evidence McMillan concludes that they are tion. On the 14th day, she was taken to the operat- Fallopian in origin. ing theatre where the donor site on the right thigh Discussion was inspected and re-dressed. Examination of the The clinical features of testicular feminization vagina showed that almost 90% of the donor skin have been described in detail by Morris (1953) and had taken, there being a small area of granulation by Hauser et al. (1957). The mechanism of the tissue at the vault on the right side. The cavity was defect which leads to the condition is uncertain, irrigated with saline and the mould re-inserted although the inherited pattern suggests a single without labial suture. Catheter drainage was dis- gene defect and consequently an enzyme defect continued at this time. (Polani, 1962). It had earlier been suggested by The patient was discharged from hospital 4 Morris that the oestrogen might be different from weeks after operation with the mould still in posi- normal in view of the unusual tissue response; tion. She was seen weekly in the out-patient de- alternatively there might be target organ resistance partment, the mould being removed at each visit to normal circulating oestrogen. and the vagina inspected. The vault granulations Current work (Deshpande et al., 1965), how- were cauterized and, after 3 months, the use of ever, shows that hormone production follows the the acrylic mould was discontinued, the patient normal male pattern. Despite this, the testicular being given a size 6 glass dilator to use daily. sex cells fail to develop normally and the Wolffian Stilboestrol 0 5 mg was given daily for 6 months. system is amost completely suppressed. Miillerian development is inhibited to some extent. Whether Follow-up these effects are due to an anti-androgen or to The patient subsequently married and was seen some unusual oestrogen produced under genetic for follow-up 6 months after marriage and 12 direction remains to be discovered. months after discharge from hospital. Vaginal Vaginal adequacy varies from case to case and examination showed the artificial vagina to be of there have been few reports of surgical correction. by copyright. normal length and healthy. Intercourse was satis- Bulska, Teter & Ruszkowski (1960) reported on factory and was achieved. the successful management of one such case. The technique of operation in our case has followed Histological report (Dr M. 0. Skelton) the standard Mclndoe-Read procedure, the latter 'The right testis measures 3 X 2 cm. At its medial having been recently described and reviewed by pole is a firm mass of pinkish-yellow tissue having Jackson (1965). It appears clear from the experi- the macroscopic appearance of muscle. On cross- ence obtained in our case that the procedure is section, the testis is of a dark red-brown colour. suitable for surgical correction in cases of testi- There is a cystic hydatid present. Microscopically cular feminization where increased length of the the testis shows immature seminiferous tubules vagina is required. lined by tall "undifferentiated" epithelial cells with It is of interest that the graft took well despite http://pmj.bmj.com/ no evidence of spermatogenesis. The interstitial the hormonal state described. cells are very abundant. At one pole of the testis is a mass of smooth muscle tissue. The left testis Summary measures 2*5 x 15 cm with a cystic hydatid pre- The creation of an artificial vagina in a patient sent. Microscopically the appearances are essen- with testicular feminization is described, details of tially similar to those of the right testis. There is investigations performed and the histo-patho- logical features being also included. no evidence of malignant change in either testis.' on October 2, 2021 by guest. Protected In a complete account of the histo-pathological Acknowledgments features in this case and in the other four cases We would like to thank Dr N. Deshpande, Dr mentioned earlier in this paper, McMillan (1966) D. Y. Wang and R. D. Bulbrook of the Division of shows that there has been Chemistry and Biochemistry, Imperial Cancer Re- early cessation of search Fund, London, and Dr Mary McMillan of this development of the sex cells in the testis and hospital for their biochemical investigations, Pro- failure of differentiation of the tubular elements fessor P. E. Polani of Guy's Hospital for the whereas, in contrast, the Leydig cells are mature chromosome analyses, Dr M. 0. Skelton for the and histo-pathological report and Dr Mary McMillan for abundant, compatible with their proven access to a histo-pathological account of testicular steroidogenic activity. The mass of smooth muscle feminization prior to publication. attached medially to the testis has the appearance of myometrium but contains no cavity. The lateral References of the testis in this contains BULSKA, M., TETER, J. & RuszKowsKI, J. (1960) For- appendage syndrome mation of the artificial vagina in male pseudo- both cysts and tubules. Some of the latter have an hermaphrodite with testicular feminization syn- unmistakably Fallopian construction and from all drome. Ginek. pol. 31, 9. Postgrad Med J: first published as 10.1136/pgmj.43.496.117 on 1 February 1967. Downloaded from

120 Case reports DESHPANDE, N., WANG, D.Y., BULBROOK, R.D. & MoRRis, J.M. (1953) The syndrome of testicular MCMILLAN, M. (1965) Hormone studies in cases of feminization in male pseudohermaphrodites. Amer. testicular feminization. Steroids, 6, 437. J. Obstet. Gynec. 65, 1192. HAUSER, G.A., KELLER, M., KOLLER, T., WENNER, R. POLANI, P.E. (1962) in: Chromosomes in Medicine & GLOOR, F. (1957) Testikulare "Feminisierung" bei (Ed. by J. L. Hamerton). Little Club Clinic Dev. Erwachsenen. Schweiz. med. Wschr. 87, 1573. Med. No. 5. National Spastics Society and Heine- JACKSON, I. (1965) lhe artificial vagina. J. Obstet. mann Medical Books, London. Gynaec. Brit. Cwlth, 72, 336. TAILLARD, W. & PRADER, A. (1957) Etude gen6tique MCMILLAN, M. (1966) Five cases of testicular femini- du syndrome de f6minization testiculaire totale et zation including one with a teratoma of the testis. partielle. J. Genet. hum. 6, 13. J. Path. Bact. (In press). Unilateral tubal twin SYLVESTER KRZANIAK B.M., B.Chir., M.R.C.O.G. Obstetric and Gynaecological Registrar, Central Middlesex Hospital, London, N. W. 10 INTRAUTERINE twin gestation occurs as often as Case report one in every eighty , but ectopic and Mrs T.S., 32 years old, Indian, Gravida III, heterotopic twins are relatively uncommon. The para I, was admitted into the Casualty Depart- heterotopic variety may take several forms, e.g: ment on 4 September 1964 with a history of (a) Coexisting intrauterine and tubal preg- increasing lower abdominal pain of 1 day's dura- nancy (Kazman & Burnett, 1953; Goodman, Elia tion, accompanied by nausea. She also volunteered & Friedell, 1960). that she had some pain in the right shoulder. This (b) Coexisting intrauterine and abdominal episode was preceded by lower abdominal pain and by copyright. gestation (Zarou & Sy, 1952; Nandi, 1953). discomfort of 3 days' duration, 8 days prior to (c) Bilateral tubal pregnancy (Evans & admission. Goyanes, 1952; Williams, 1957). Her menstruation started at the age of 15. The (d) Coexisting ovarian and intrauterine twins periods were regular occurring every 28 days and (Rannels, 1953; Lawson & Chouler, 1955). lasting 4 days. The last menstrual period occurred Primary ovarian twin pregnancies were reported on 16 June 1964. Her husband had died of 'sudden (Modavi, 1962; Green & West, 1963). This is the heart attack' on 26 June 1964 and she attributed rarest form of twinning. her amenorrhoea to shock but a Primodos preg- Unilateral tubal twin pregnancy is still very nancy test on 14 August 1964 was positive. rare. In 1955 Unger reported one case and, review- Her only child was born in 1949 the third stage ing the world's literature, stated that by then there being complicated by a retained placenta. She also http://pmj.bmj.com/ were only seventy-nine cases. This figure was con- had had two abortions at 10 weeks gestation in firmed by others (Bucklin & Myint, 1959; Borrow 1949 and 1954. & Schreiber, 1961 ; Loh & Loh, 1962). There was no history of serious illnesses or Bucklin & Myint (1959), however, reported their operations. case as the eightieth, whilst in Loh's (Loh & Loh, On examination her general condition was satis- 1962) estimation this was the eighty-third case re- factory. The temperature was 99'F. Her pulse was

ported in the literature. Borrow & Schreiber (1961), regular at the rate of 80/min. Blood pressure was on October 2, 2021 by guest. Protected on the other hand, said that their two cases brought 100/60 mmHg. There was no evidence of shock. the total number of unilateral tubal twins to The breasts were active. Cardiovascular and res- eighty-one cases. piratory systems were normal. The lower abdomen This disparity can be explained by the fact that was slightly distended, the hypogastrium was Bucklin & Myint (1959) did not take into account tender and there was marked rebound tenderness three cases published in 1957 and 1958 (Fill & in both iliac fossae. An ill-defined mobile, tender Ross, 1957; Fara & Varga, 1957; Demick & swelling was palpable in the right iliac fossa. Cavanagh, 1958). Borrow seemed unaware of the There was no vaginal bleeding or discharge. The above three publications as well as that of Bucklin uterus was enlarged and corresponded in size to in 1959, and Loh & Loh (1962) made no reference an 8-week gestation. The cervix was congested, to the two Borrow cases. closed and there was marked cervical excitatory If the above corrections are made respectively, pain. Both fornices and the pouch of Douglas the total number of published unilateral tubal were very tender. pregnancies by 1962 was eighty-six. There was a cystic mobile swelling 10 cm in