5th Joint Meeting of ESPU-SPU - Virtual

S8: DSD

Moderators: Katja Wolffenbuttel (Netherlands)

ESPU-SPU Meeting on Friday 24, September 2021, 11:20 - 12:02


11:20 - 11:23
S8-1 (SO)

★ MAJORITY OF FEMALES WITH A LIFE-LONG EXPERIENCE OF CAH AND PARENTS DO NOT CONSIDER FEMALES WITH CAH TO BE INTERSEX

Konrad SZYMANSKI 1, Richard RINK 2 and Benjamin WHITTAM 2
1) Riley Hospital for Children, Pediatric Urology, Indianapolis, USA - 2) Riley Hospital for Children at IU Health, Pediatric Urology, Indianapolis, USA

PURPOSE

To assess opinions of females with CAH, and their parents, about designating this population “intersex,” particularly in legislation about genital surgery during childhood.

MATERIAL AND METHODS

Online survey of females with CAH (46XX,16+ years old) and independently recruited parents of girls with CAH (2019-2020) diagnosed in first year of life, living in the United States.  A multidisciplinary medical team involved in CAH care drafted the survey with women with CAH and parents.  Fisher’s exact test was used to compare female and parent responses.

RESULTS

Of 57 females with CAH participating (median age: 24 years, 71.9% post-secondary degree), 93.0% underwent genital surgery at median 1-2 years old. While 89.5% did not endorse the intersex designation for CAH, 5.3% did (5.3% provided no answer).  Most CAH females (63.2%) believed CAH females should be considered separately in “any laws banning or allowing surgery of children’s genitals” (19.3% disagreed, 17.5% neutral, 0.0% no answer).

Overall, 125 parents of females with CAH participated (parent/child median ages: 41/8, 80.0% post-secondary degree), 80.0% of their children underwent surgery at median <1 year old.  While 96.0% of parents did not endorse the intersex designation for CAH, 1.6% did (2.4% no answer), similar to females (p=0.17).  Most parents (79.4%) believed CAH females should be considered separately in legislation (9.5% disagreed, 6.4% neutral, 4.8% no answer), a slightly higher percentage than females (p=0.01). 

CONCLUSIONS

The majority of females with CAH and their parents believe CAH should be excluded from the intersex designation and be considered separately in legislation pertaining to genital surgery in childhood.


11:23 - 11:26
S8-2 (SO)

SEXUAL FUNCTION IN ADULT FEMALES AFTER FEMINISING GENITOPLASTY FOR CONGENITAL ADRENAL HYPERPLASIA

Jan TRACHTA 1, Imran MUSHTAQ 2, Natalia PETRASOVA 1, Blanka ROUSKOVA 1 and Richard SKABA 1
1) Motol University Hospital, Paediatric Surgery Department, Prague, CZECH REPUBLIC - 2) Great Ormond Street Hospital, Department of Paediatric Urology, London, UNITED KINGDOM

PURPOSE

To investigate long-term sexual function in adult women after feminising genitoplasty (FGP) for Congenital Adrenal Hyperplasia (CAH).

MATERIAL AND METHODS

We retrospectively reviewed medical files of all patients who underwent FGP from 1996 to 2018. Patients with CAH older than 16 years were asked to answer three standardised questionnaires evaluating their current mental well-being (WHO-5 Well-Being Index), lower urinary tract symptoms (ICIQ-FLUTS) and sexual function (GRISS). The anonymised answers were compared to a control group of 50 healthy females. Student t-test, Pearson's χ2 test, Fisher's exact test and Spearman's rank correlation coefficient were performed. p-value less than 0.05 was considered significant.

RESULTS

From 106 patients who underwent FGP, 64 were included and 32, aged 17 to 40 years (mean 25.5), answered the questionnaires (50% response rate). 11 patients underwent clitoridectomy and 21 modern two staged FGP.  There were statistically signifiant differences between CAH and control groups as to the proportion living in commited partnerships (28% and 84%, p = 0.0000), having sexual intercourse (13% and 92%, p = 0.0000) and having their own children (13% and 36%, p = 0.0369). The current mental well-being of the groups was not statistically different (p = 0.82). The mean overall GRISS score was 4 (range 1-7) in CAH group compared to 1 (range 1-9) in the controls, with infrequency and vaginismus representing the least favourable subscales (mean 5).

CONCLUSIONS

Partnership, offspring, sexual frequency and function are impaired in the adult CAH females after FGP, however, the overall mean GRISS score is below the pathological level of 5.


11:26 - 11:29
S8-3 (SO)

WHAT DO PATIENTS AND PARENTS SAY ABOUT PARENTS' ABILITY TO CHOOSE EARLY GENITAL SURGERY FOR GIRLS WITH CAH?

Konrad SZYMANSKI 1, Luis BRAGA 2, Paul KOKOROWSKI 3, Brian LELAND 4 and On Behalf Of The LIFE WITH CONGENITAL ADRENAL HYPERPLASIA STUDY GROUP 5
1) Riley Hospital for Children at IU Health, Pediatric Urology, Indianapolis, USA - 2) McMaster Children's Hospital, McMaster University, Division of Pediatric Urology, Hamilton, CANADA - 3) Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Pediatric Urology, Los Angeles, USA - 4) Indiana University School of Medicine, Indianapolis, IN; Charles Warren Fairbanks Center for Medical Ethics, Indianap, Department of Pediatrics and Division of Pediatric Critical Care Medicine, Indianapolis, USA - 5) Riley Hospital for Children at IU Health, Indianapolis, USA

PURPOSE

To determine opinions of females with CAH, and parents, about parent's ability to choose early genital surgery for girls with CAH.

MATERIAL AND METHODS

Online survey of CAH females (46XX,16+ years old) and independently recruited parents (2019-2020) diagnosed in first year of life in the United States. A multidisciplinary medical team, CAH women and parents drafted the survey. Fisher's exact test was used.

RESULTS

Of 57 CAH females (median age: 24 years), 93.0% underwent genital surgery (median 1-2years old). Most females (79.0%) believed legislation prohibiting surgery in childhood would cause harm. Most (64.9%) believed a ban "would have been harmful to me" (24.6% not harmful, 10.5% neutral). Most females (70.2%) believed a ban undermined parental rights to make medical decisions in their child's best interest. While 14.0% believed a ban was in the best interest of CAH females, 75.4% did not (10.5% neutral).

For 125 parents of CAH females (parent/child median ages: 41/8), 80.0% of children underwent surgery (median <1year old). Most parents (93.6%) believed legislation prohibiting surgery in childhood would cause harm. Most (76.8%) believed a ban "would have harmed my daughter" (12.8% no harm, 4.8% neutral, 5.6% no answer). Parents were more likely than CAH females to oppose a ban (p<=0.02). Most parents (90.4%) believed a ban undermined parental rights. While 3.2% believed a ban was in the best interest of CAH females, 94.4% did not (2.4% neutral).

CONCLUSIONS

Majority of females with CAH and parents support parents' ability to choose timing of potential genital surgery, opposing a moratorium on surgery in childhood.


11:29 - 11:32
S8-4 (SO)

LOWER URINARY TRACT SYMPTOMS IN ADULT FEMALES AFTER FEMINISING GENITOPLASTY FOR CONGENITAL ADRENAL HYPERPLASIA

Jan TRACHTA 1, Imran MUSHTAQ 2, Natalia PETRASOVA 1, Blanka ROUSKOVA 1 and Richard SKABA 1
1) Motol University Hospital, Paediatric Surgery Department, Prague, CZECH REPUBLIC - 2) Great Ormond Street Hospital, Paediatric Urology Department, London, UNITED KINGDOM

PURPOSE

To investigate long-term lower urinary tract function in adult women after feminising genitoplasty (FGP) performed for Congenital Adrenal Hyperplasia (CAH).

MATERIAL AND METHODS

We retrospectively reviewed medical files of all patients who underwent FGP from 1996 to 2018. Patients with CAH older than 16 years were asked to answer three standardised questionnaires evaluating their current mental well-being (WHO-5 Well-Being Index), lower urinary tract symptoms (ICIQ-FLUTS) and sexual function (GRISS). The anonymised answers were compared to a control group of 50 healthy females. Student t-test, Pearson's χ2 test, Fisher's exact test and Spearman's rank correlation coefficient were performed. p-value less than 0.05 was considered significant.

RESULTS

From 106 patients who underwent FGP, 64 were included and 32, aged 17 to 40 years (mean 25.5), answered the questionnaires (50% response rate). 11 patients underwent clitoridectomy and 21 modern two staged FGP.  There was no significant difference between current mental well-being of operated and control group (WHO-5 mean score 60 and 64 respectively, p-value 0.82). We found no significant difference in the LUTS subscales of filling, voiding and incontinence as well as in the overall LUTS score (ICIQ-FLUTS overall mean score 3.5 and 3 respectively, p-value 0.43).

CONCLUSIONS

There was no higher prevalence of long-term lower urinary tract dysfunction in CAH adult female patients after FGP in our analysed group.


11:32 - 11:35
S8-5 (SO)

IMMUNOHISTOCHEMICAL EVALUATION REQUIRED FOR CORRECT DIAGNOSIS OF OVOTESTICULAR DSD AND GONADAL MALIGNANCY RISK ASSESSMENT

Katja WOLFFENBUTTEL 1, Remko HERSMUS 2, Hans STOOP 2, Martine COOLS 3, Katharina BIERMANN 2, J.W. OOSTERHUIS 2 and Leendert LOOIJENGA 4
1) Erasmus MC - Sophia Children's Hospital, Paediatric Urology, Rotterdam, NETHERLANDS - 2) Erasmus Medical Center, Pathology, Rotterdam, NETHERLANDS - 3) Ghent University Hospital, Pediatrics, Ghent, BELGIUM - 4) Princess Máxima Center for Pediatric Oncology, Utrecht, NETHERLANDS

PURPOSE

Ovotesticular DSD (OTDSD) is a rare condition and, despite the clear definition, incorrect diagnoses have been reported. The aim of this study was to evaluate the accuracy of the diagnosis OTDSD and the added value of immunohistochemistry (IHC) in the histological assessment of these gonads by expert pathologists.

MATERIAL AND METHODS

Series A consists of institutional histological data of 15 OTDSD patients treated between 1985-2015. In addition, a search in a national pathology database yielded gonadal material of 13 OTDSD patients treated in other institutes between 1993 and 2015 (series B). Available gonadal material was analyzed with IHC using germ cell specific and gonadal differentiation markers (DDX4, TSPY, OCT3/4, KITLG, SOX9, FOXL2) and slides were reviewed by two expert pathologists.

RESULTS

Series A: karyotype was 46,XX in 10, chimeric in 2 and mosaic in 3 patients. Histology of 29 gonads showed 20 ovotestes (OT), 5 ovaries (O) and 4 testes (T). Review of available slides showed normal germ cell (gc) development in the testicular parts in 3, gc absence in 7 and dysgenetic areas with precursor Germ Cell Neoplasia In Situ (pre-GCNIS) in 2 patients, both with mosaic karyotype. Moreover, combined gonadoblastoma (GB) and invasive GCN was diagnosed in an abdominal OT of a 23 years old 46,XX OTDSD patient.
Series B: the diagnosis OTDSD after review of all slides was confirmed in only 3/13 cases. Pre-GCNIS was present in a case with mosaic karyotype.

CONCLUSIONS

IHC and review of the histology by an expert pathologist are required for correct diagnosis of OTDSD. Series B confirms incorrect diagnosis in 77%. GB with GCN was found in 1/18 and pre-GCNIS in 3/18 patients with confirmed OTDSD. Although GCN prevalence in this series, 1/18 (6%), is consistent with the literature, tumor risk could be higher if these gonads were left in situ, given the pre-GCNIS found in 3/18 (17%) patients.


11:35 - 11:38
S8-6 (SO)

OVERVIEW OF THE GENETICS IN DISORDERS OF SEX DEVELOPMENT AT AN ACADEMIC HOSPITAL IN PRETORIA, SOUTH AFRICA: WHAT IS GOING ON?

Nico LOURENS 1, Tanya KEMP 2 and Maria KARSAS 3
1) Steve Biko Academic Hospital, Department of Urology, Pretoria, SOUTH AFRICA - 2) Steve Biko Academic Hospital, Department of Adult Endocrinology, Pretoria, SOUTH AFRICA - 3) Steve Biko Academic Hospital, Department of Pediatric Endocrinology, Pretoria, SOUTH AFRICA

PURPOSE

The incidence of DSD in the general population is estimated at between 1 in 4500-5000, but the frequency of specific types of DSD presenting at birth is unknown. Klinefelter and Turner Syndromes appear commonly, while 46XX DSD conditions such as CAH are rarer and true Ovotesticular DSD rarest of all. This study evaluated the frequency and genetics of DSDs presenting to an academic hospital in Pretoria, South Africa.

MATERIAL AND METHODS

A retrospective case series analysis was conducted on patient data from databases starting in 2000. Data was obtained anonymously and analysis performed.

RESULTS

A total of 185 patients were identified, 44 adult and 141 pediatric patients. The most common diagnosis in adults was Turner Syndrome (34,09%) followed by 46XX OT-DSD (20,45%) and CAH (13,64%). In the pediatric group 46XX OT-DSD (33,90%) occurred most commonly, followed by CAH (24,58%) and 46XY undervirilized males (15,25%). Moreover, in the pediatric OT-DSD group, 61,36% of patients tested negative for SRY-gene translocation, a finding not typically seen in 46XX males.

CONCLUSIONS

The spectrum of DSDs presenting in this study is different from what is traditionally seen in the Western world. True OT-DSD occurs significantly more frequently, and the underlying genetics also differ from what is usually seen, with most patients testing negative for SRY-gene translocation. The underlying contributory factors are unknown and need to be explored further.


11:38 - 11:41
S8-7: Withdrawn (video presentation not uploaded)
 
11:41 - 12:02
Discussion