TEMPLATE DESIGN © IntroductionResults Conclusions References A case series of XY females in the first Malaysian PAG clinic NurZaireena Z.,* Amelia A.Z., *NurAzurah A.G., ***S. R. Grover, **Suraya Aziz,* Sharul Rizal Samsury, * Z. A. Mahdy * Department of O & G, **Department of Radiology, UKMMC, Kuala Lumpur, Malaysia; ***Department of Paediatric and Adolescent Gynaecology, Royal Childrens’ Hospital Melbourne, Australia  XY females are one of the main group under the disorder of sexual development (DSD), or previously known as intersex condition. 1  They may present with incomplete masculinized external genitalia, ambiguous genitalia or even a complete female external genitalia with an XY chromosome.  This can be due to disorders of testicular development or disorders in androgen synthesis. 2 Abnormal gene expression in the cascade of testis determination or development leads to 46, XY DSD which includes (complete or partial gonadal dysgenesis, with or without syndromic phenotype, ovotesticular DSD and testicular regression syndrome). Objectives: To report a case series of XY females referred to the first Paediatric and Adolescent Gynaecology (PAG) Clinic in Malaysia and the challenges in making accurate diagnosis. Methods: All cases of XY females referred and managed in the first two years of the PAG clinic, UKMMC were included since Clinical presentations, investigation results, treatment given and outcome are described. Objectives & Methods Preliminary informationInitial diagnosisFurther information Final revised diagnosis Case 1: XY karyotype with phenotypic female  Inguinal masses noted at 3yo  Gonadectomy  testes(but no HPE available)  Commenced low dose oestrogen at 12yo Complete Androgen Insensitivity Syndrome (CAIS)  Repeat usg after oestrogen  no uterus present.  Scanty pubic and axillary hair CAIS Case 2: Primary amenorrhoea at 24yo.  Minimal medical contact.  No secondary sexual characteristics ( 3 sisters all menstruating).  BMI 18; No axillary hair, normal external genitalia, vagina 1cm blind ending.  MRI- vagina, cervix seen with rudimentary uterus.  No ovaries seen. USG - reported rudimentary uterus Complete Androgen Insensitivity Syndrome (CAIS)  No hormonal results available.  Gonadectomy planned – but patient postponed.  Planned commencement of oestrogen for pubertal development.  Poor breast development may be secondary to being underweight Probable CAIS **presence of a uterus does not fit this diagnosis?? 46XY gonadal dysgenesis Case 3: primary amenorrhoea at 18. No secondary sexual characteristics. Is sexually active. Examination: breasts Tanner 2, normal female non oestrogenised external genitalia  LH 31.3 (  ), FSH 2.3; oestradiol 40 (  ).  MRI-left testes identified, right side not identified, prepubertal uterus. Laparoscopy:bilateral gonadectomy performed Androgen Insensitivity Syndrome (AIS)  Following oestrogen usage  uterus identified, development of pubic and axillary hair.  now menstruating. Progestogens now used cyclically 46XY gonadal dysgenesis Case 4: First seen at 3yo with developmental delay, and dysmorphic features.  Karyotype 46XY. SRY gene present.Gonadectomy at 5yo. No HPE available. No uterus identified. 46 mixed gonadal dysgenesis (in view of the absent uterus) However with ERT – now menstruating. Added cyclic progestogens. 46XY Gonadal Dysgenesis Case 5: primary amenorhoea at 18, No secondary sexual characteristics, normal female genitalia. MRI no uterus or ovaries. Laparoscopy with gonadectomy, no uterus seen. HPE – streak gonads. 46 XY Gonadal Dysgenesis – but inconsistent with finding of no uterus After oestrogen therapy – menstruated. Now using cyclic progestogens 46XY Gonadal Dysgenesis Case 6 : Ambiguous genitalia (younger sister of case 5). U/s: rudimentary uterus 3.2 x2.0cm  Chromosomal study: 46 XY, SRY gene positive  bilateral gonadectomy at 4 years old 46XY partial gonadal dysgenesis Started on estrogen therapy46, XY Partial Gonadal Dysgenesis Case 7: Normal female genitalia at birth. Presented with right inguinal swelling and clitoromegaly and labioscrotal at 11yo  Gonadectomy done. Intraoperative : no uterus nor ovaries. Blunt vaginal opening.  Karyotyping done noted 46xx/46xy. True hermaphroditeAbsent uterus, confirmed by ultrasound scan and never menstruated. On estrogen since age XY/46XX mixed gonadal dysgenesis Figure 1 : Arrow shows streak gonad seen laparoscopically in Case 5. Fig 3 and 4 (case 3) (Fig3) Sagittal T1WI showing a small uterus (white arrows) of prepubertalage with presence of vagina,normally placed posterior to the bladder (block arrow). Both ovaries are not identified. (Fig4) Coronal T2WI depicted a hypointense oval structure (thick arrow) in the left hemipelvis which most likely represent intra-abdominal testis. 1. Risk of malignancy in CAIS is %. Monitor intraabdominal testes as there is a 2-5% risk of malignancy. Malignancy risk in the gonad is determined by the diagnosis 3. - CAIS - risk of malignancy in the intra abdominal - testes is 2-5 %,extra abdominal testes risk is 1%. - PAIS – risk of malignancy is up to 50%. - Complete GD – malignancy risk is 30% 2.In CAIS cases, the testes is able to produce testosterone which undergoes peripheral aromatisation for breast development. Hence in CAIS cases, removing them after puberty may allow for their own breast development whereas removing them early in childhood prevents this. Also, early gonadectomy prevents these patients from giving their own informed consent, and they will require commencement of lifelong hormonal replacement therapy. 3.Beware assessments suggesting an absent uterus in the context of low oestrogens as the uterus may be very small and missed on USG, MRI and at laparoscopy ( note case 3, 4 and 5). 4. Reduced bone density is a risk in these women. Patients need to be educated on this and make the necessary lifestyle modifications and supplements and have regular BMD checks and ensure adequate HRT in those without endogenous testosterone or oestrogen. 5. Gender identity is not usually an issue in those with CAIS or 46XYGD. 1.Lee PA, Houk CP, Ahmet F, et al. In collaboration with participants in the international consensus conference on intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology. Consensus statement on management of intersex disorders. Pediatrics 2006;118: Damian D, Paulo S. Disorder of sexual development: Still a big challenge. J Pediatr Endocrinol Metab 2007;20: Minto, Catherine. The XY female. In: Paediatric and Adolescent Gynaecology, Adam Balen, Sarah Creighton, Melanie C. Davies, Jane MacDougall, Richard Stanhope, eds., pp Cambridge University Press, UK. Figure 2 : Arrow shows uterus seen laparoscopically before hormonal treatment in case 5