ESPE Abstracts (2022) 95 FC6.3

1Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom; 2Department of Pediatric Endocrinology, Ghent University Hospital, Ghent, Belgium; 3Department of Pathology, Ghent University Hospital, Ghent University, Ghent, Belgium; 4Unidade de Endocrinologia do Desenvolvimento/ LIM42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; 5State University of Campinas (Unicamp), School of Medical Sciences, Interdisciplinary Group for Study of Sex Determination and Differentiation (GIEDDS), Campinas, Brazil; 6Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom; 7Amsterdam UMC location Vrije Universiteit Amsterdam, Department. of Paediatric Endocrinology, Amsterdam, Netherlands; 8Amsterdam Reproduction & Development, Amsterdam, Netherlands; 9Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands; 10Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 11Department of pediatric endocrinology of Ukrainian Scientific Center of Endocrine Surgery, Kyiv, Ukraine; 12Human Developmental Genetics, Institute Pasteur, Paris, France; 13Department Hospital of Woman and Child, Pediatric Unit, Center for Rare Endocrine Conditions (Endo-ERN), IRCCS - S.Orsola-Malpighi University Hospital, Bologna, Italy; 14División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina; 15Department of Pediatrics, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey; 16Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland; 17Radboud University Medical Centre, Amalia Children’s Hospital, Department of Pediatrics, Nijmegen, Netherlands; 18Department of Pediatrics, division of pediatric endocrinology and DSD Center of expertise, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, Netherlands; 19Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany; 20Department of Pediatrics, Lady Ridgeway Hospital, Colombo, Sri Lanka; 21Department of Pediatrics, division of Pediatric Endocrinology, All India Institute of Medical Sciences, New Delhi, India; 22Paediatric Endocrinology and Diabetes, Heidelberg University Children´s Hospital, Heidelberg, Germany; 23Department of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland; 24Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Christian-Albrechts-University of Kiel, Kiel, Germany; 25Endocrinology and diabetes, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania; 26Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, United Kingdom; 27Department of Pediatrics, Endocrine Unit, Vita-Salute San Raffaele University, IRCSS San Raffaele, Milan, Italy; 28Wessex Clinical Genetics Service, Princess Anne Hospital, University Hospital Southampton NHS Trust, Southampton, United Kingdom; 29Department of Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; 30Department of Paediatric Endocrinology and Diabetes, Birmingham Women’s and Children’s Hospital NHS trust, Birmingham, United Kingdom; 31Department of Paediatrics, University of Colombo, Colombo, Sri Lanka; 32Marmara University, School of Medicine, Department of Paediatric Endocrinology and Diabetes, Istanbul, Turkey; 33Başkent University, Medical Faculty, Department of Pediatric Endocrinology, Istanbul Hospital, Istanbul, Turkey; 34Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy; 35Department of Paediatrics - UMHAT 'Sv.Marina', Medical University of Varna, Varna, Bulgaria; 36Children's Surgery Centre, Faculty of Medicine, Vilnius University, Vilnius, Lithuania; 37Department of Endocrinology, Yerevan State Medical University, Yerevan, Armenia; 38Endocrinology, Barts and The London School of Medicine and Dentistry, London, United Kingdom; 39Division of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University of Lübeck, Lübeck, Germany; 40Department of Paediatrics, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom

Background/Aims: 46,XY gonadal dysgenesis (GD) is classified as complete (CGD) or partial (PGD) depending on gonadal morphology and function. In contrast to the typical female external genitalia in CGD, the phenotype of PGD is variable depending on androgen production. A diagnosis of PGD is based on clinical/biochemical features, gonadal histology and genetic findings. The aim of this study is to characterise these features, particularly histological, in a large cohort of PGD using CGD as a comparator, and to determine germ cell cancer (GCC) risk in each group.

Methods: Patients with 46,XY GD were identified from the I-DSD Registry. Histology data were submitted as local written reports (n=70), digital images (n=16) or using a proforma (n=197). CGD inclusion criteria: (1) 46,XY (2) typical female genitalia (3) presence of Mullerian duct derivatives and/or undetectable AMH (4) if pubertal, elevated LH/FSH. PGD: (1) 46,XY (2) atypical genitalia (3) at least one of the following: (A) evidence of GD (AMH in-between male and female references, low inhibin B or Mullerian derivatives), (B) histology consistent with PGD, or (C) pathogenic gene variants associated with GD. Group categories: CGD, PGD assigned female at birth (PGDf), PGD assigned male at birth (PGDm).


  CGD n=108 PGDf n=83 PGDm n=109
Median age of presentation (interquartile range) Yr 14.9 (10.5) 0.79 (13.8) 0.5 (2.9)
Median age of gonadectomy (Interquartile range) Yr 15.8 (8.5) 5.2 (13.6) 4.5 (8.6)
Not done

90/108 (83.3%)
0/108 (0%)
6/108 (5.6%)

54/83 (65.1%)
2/83 (2.4%)
20/83 (24.1%)

23/109 (21.1%)
17/109 (15.6%)
55/109 (50.5%)
Gonadal regression (Uni/bilateral) 6/108 (5.6%) 7/83 (8.4%) 7/109 (6.4%)
Gonadal GCC (in situ lesion or invasive) 30/95 (32%) 12/60 (20%) 5/40 (13%)*
Type of GCC (Per gonad)
Germ cell neoplasia in situ
Other GCC
Non germ cell gonadal tumors

19/44 (43.2%)
12/44 (27.3%)
4/44 (9.1%)
7/44 (15.9%)
0/44 (0%)

9/22 (40.1%)
4/22 (18.2%)
3/22 (13.6%)
4/22 (18.2%)
2/22 (9.1%)

3/8 (37.5%)
0/8 (0%)
2/8 (25%)
3/8 (37.5%)
0/8 (0%)
*P<0.05 vs CGD

Conclusion:The higher frequency of GCC in CGD (32%) compared to PGDf (20%) and PGDm (13%) can be partly explained by the timing of gonadectomy. A centralised expert pathology review of the reports is now underway to correlate gonadal GCC risk with gonadal morphology and patient characteristics (e.g. virilisation), and to better characterise PGD from a histological perspective. Such studies are needed to predict GCC risk, particularly in PGDm.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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