Evidence map›Paper›PMID 40208111›Full record

ArticleThe Journal of clinical endocrinology and metabolism2025

Phenotypic Variation and Pubertal Outcomes in Males and Females With 46,XY Partial Gonadal Dysgenesis.

Rieko Tadokoro-Cuccaro, Ieuan A Hughes, Martine Cools, Koen van de Vijver, Berenice Bilharinho de Mendonça, Sorahia Domenice, Rafael Loch Batista, Renata Thomazini Dallago, Elaine F Costa, Nathalia Lisboa Gomes and 45 more

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Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

55 authors.

Rieko Tadokoro-CuccaroDepartment of Paediatrics, University of Cambridge, Cambridge, CB2 0QQ, UK.ORCID 0000-0003-4012-7033
Ieuan A HughesDepartment of Paediatrics, University of Cambridge, Cambridge, CB2 0QQ, UK.
Martine CoolsDepartment of Internal Medicine and Paediatrics, Ghent University, 9000 Ghent, Belgium.
Koen van de VijverDepartment of Pathology, Ghent University, 9000 Ghent, Belgium.
Berenice Bilharinho de MendonçaEndocrinology Division, Internal Medicine Department, Development Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42) and SELA (Laboratório de Sequenciamento em Larga Escala), Medical School, University of São Paulo, 05403-900 Sao Paulo, Brazil.
Sorahia DomeniceEndocrinology Division, Internal Medicine Department, Development Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42) and SELA (Laboratório de Sequenciamento em Larga Escala), Medical School, University of São Paulo, 05403-900 Sao Paulo, Brazil.
Rafael Loch BatistaEndocrinology Division, Internal Medicine Department, Development Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42) and SELA (Laboratório de Sequenciamento em Larga Escala), Medical School, University of São Paulo, 05403-900 Sao Paulo, Brazil.
Renata Thomazini DallagoEndocrinology Division, Internal Medicine Department, Development Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42) and SELA (Laboratório de Sequenciamento em Larga Escala), Medical School, University of São Paulo, 05403-900 Sao Paulo, Brazil.
Elaine F CostaEndocrinology Division, Internal Medicine Department, Development Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42) and SELA (Laboratório de Sequenciamento em Larga Escala), Medical School, University of São Paulo, 05403-900 Sao Paulo, Brazil.
Nathalia Lisboa GomesDivision of Endocrinology, Santa Casa de Belo Horizonte, Belo Horizonte 30150-221, Brazil.
Andréa T Maciel-GuerraSchool of Medical Sciences, Interdisciplinary Group for Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (Unicamp), 13083-887 Campinas, Brazil.
Gil Guerra-JuniorSchool of Medical Sciences, Interdisciplinary Group for Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (Unicamp), 13083-887 Campinas, Brazil.ORCID 0000-0002-2991-7678
Juliana Gabriel Ribeiro de AndradeSchool of Medical Sciences, Interdisciplinary Group for Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (Unicamp), 13083-887 Campinas, Brazil.
Angela Lucas-HeraldDevelopmental Endocrinology Research Group, University of Glasgow, Glasgow, G51 4TF, UK.
Jillian BryceOffice for Rare Conditions, University of Glasgow, Glasgow, G51 4TF, UK.
Sabine HannemaDepartment of Paediatric Endocrinology, Amsterdam UMC location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, the Netherlands.
Anders JuulDepartment of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark.ORCID 0000-0002-0534-4350
Evgenia GlobaUkrainian Scientific and Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of MOH of Ukraine, Kyiv 01021, Ukraine.
Ken McElreaveyInstitut Pasteur, Université Paris Cité, Human Developmental Genetics Unit, Paris F-75015, France.
Federico BaronioDepartment Hospital of Woman and Child, Pediatric Unit, Center for Rare Endocrine Conditions (Endo-ERN), IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy.
Rodolfo ReyCONICET-FEI-Division of Endocrinology, Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina.ORCID 0000-0002-1100-3843
Jimena Lopez DacalCONICET-FEI-Division of Endocrinology, Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina.
Feyza DarendelilerDepartment of Pediatric Endocrinology, Istanbul University Istanbul Faculty of Medicine, Istanbul 34098, Turkey.
Sukran PoyrazogluDepartment of Pediatric Endocrinology, Istanbul University Istanbul Faculty of Medicine, Istanbul 34098, Turkey.
Zofia KolesińskaDepartment of Pediatric Endocrinology and Rheumatology, Karol Jonscher Clinical Hospital, Poznan University of Medical Sciences, 60-572 Poznan, Poland.
Marek NiedzielaDepartment of Pediatric Endocrinology and Rheumatology, Karol Jonscher Clinical Hospital, Poznan University of Medical Sciences, 60-572 Poznan, Poland.
Hedi L Claahsen-van der GrintenDepartment of Pediatrics, Radboud University Medical Centre, Amalia Children's Hospital, 6525 GA Nijmegen, The Netherlands.
Erica L T van den AkkerDepartment of Pediatrics, Division of pediatric endocrinology and DSD Center of expertise, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, 3015 CN Rotterdam, The Netherlands.
Gloria HerrmannDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, 89075 Ulm, Germany.
Navoda AtapattuDepartment of Pediatrics, Lady Ridgeway Hospital, Colombo 08, Sri Lanka.ORCID 0000-0002-3398-2536
Vandana JainDepartment of Pediatrics, Division of Pediatric Endocrinology, All India Institute of Medical Sciences, New Delhi 110029, India.
Rajni SharmaDepartment of Pediatrics, Division of Pediatric Endocrinology, All India Institute of Medical Sciences, New Delhi 110029, India.
Markus BettendorfPaediatric Endocrinology and Diabetes, Heidelberg University Children´s Hospital, 69120 Heidelberg, Germany.
Daniel KonradDivision of Endocrinology and Diabetes, University Children's Hospital Zurich, University Zurich, 8032 Zurich, Switzerland.ORCID 0000-0001-9067-4356
Nina Lenherr-TaubeDivision of Endocrinology and Diabetes, University Children's Hospital Zurich, University Zurich, 8032 Zurich, Switzerland.
Paul Martin HolterhusDepartment of Paediatric Oncology and Rheumatology, Paediatric Endocrinology and Diabetes, University of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Simona FicaEndocrinology and Diabetes, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania.
Mars SkaeDepartment of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester M13 9WL, UK.
Gianni RussoDepartment of Pediatrics, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Marianna Rita StancampianoDepartment of Pediatrics, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Gabriella GazdaghWessex Clinical Genetics Service, Princess Anne Hospital, University Hospital Southampton NHS Trust, Southampton, SO16 5YA, UK.
Justin H DaviesDepartment of Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK.
Zainaba MohamedDepartment of Paediatric Endocrinology and Diabetes, Birmingham Women's and Children's Hospital NHS Trust, Birmingham, B4 6NH, UK.ORCID 0000-0003-1337-7889
Sumudu Nimali SeneviratneDepartment of Paediatrics, University of Colombo, Colombo 08, Sri Lanka.ORCID 0000-0003-2960-9269
Tülay GüranDepartment of Paediatric Endocrinology and Diabetes, Marmara University, School of Medicine, 34841 Istanbul, Turkey.ORCID 0000-0003-2658-6866
Ayla GüvenEmeritus Pediatric Endocrinologist, Başkent University Faculty of Medicine, Department of Child Health and Diseases, Istanbul Hospital, 34770 İstanbul, Turkey.
Malgorzata WasniewskaDepartment of Human Pathology of Adulthood and Childhood, University of Messina, 98122 Messina, Italy.
Vilhelm MladenovDepartment of Paediatrics - UMHAT 'Sv.Marina', Medical University of Varna, 9010 Varna, Bulgaria.
Gilvydas VerkauskasFaculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania.
Renata MarkosyanDepartment of Endocrinology, Yerevan State Medical University, Yerevan 0025, Armenia.
Marta KorbonitsEndocrinology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1A 7BE, UK.ORCID 0000-0002-4101-9432
Olaf HiortDivision of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University of Lübeck, 23562 Lübeck, Germany.ORCID 0000-0001-7490-4983
Isabel Viola Frielitz-WagnerDivision of Pediatric Endocrinology and Diabetes, Department of Pediatric and Adolescent Medicine, University of Lübeck, 23562 Lübeck, Germany.
S Faisal AhmedDevelopmental Endocrinology Research Group, University of Glasgow, Glasgow, G51 4TF, UK.
Ajay ThankamonyDepartment of Paediatrics, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK.ORCID 0000-0001-6290-3553

Funding

Cambridge University
6 · The paper itself

Abstract

background46,XY gonadal dysgenesis is classified as complete (CGD) or partial (PGD) subtypes. The phenotype of PGD and the long-term outcome is not clearly defined.

objectiveTo evaluate clinical features and pubertal outcome of PGD in a large cohort, using CGD as a comparator for diagnostic clarity.

methodsPatients with 46,XY GD were identified from the I-DSD Registry and data on phenotype, genetics, biochemistry, gonadal histology, and pubertal development were collated in 3 categories; CGD (n = 100), PGD assigned female (PGDf, n = 107), and male (PGDm, n = 103) at birth.

resultsMost individuals with PGD presented with atypical genitalia in infancy, though, 18% of PGDf presented with delayed puberty and 8% with virilization. A genetic etiology was identified in 42% of the cohort, with common gene defects in SRY and WT1 in CGD and NR5A1 in PGD. Gonadal pre-/malignancy was found in 33.8% in CGD, 19.7% in PGDf, and 8.8% in PGDm. Among the PGDm (>13 years) with at least 1 gonad, 80% had spontaneous pubertal onset and 59% achieved Tanner G5 without hormone treatment. Labioscrotal gonads at presentation and testosterone response to human chorionic gonadotropin predicted onset of spontaneous puberty. In PGDf with gonads, 42% developed spontaneous virilization at puberty. Sex was reassigned in 16.1% and 5.3% of individuals with PGDf and PGDm, respectively.

conclusionThis study highlights the heterogeneous phenotype of PGD and the consequent diagnostic challenge. Many PGD patients with preserved gonads have the potential to develop puberty spontaneously, though further study is needed to determine the risk of developing gonadal tumors.

Indexed as

Gonadal Dysgenesis, 46,XYPubertyAdolescentAdultChildChild, PreschoolCohort StudiesFemaleHumansInfantInfant, NewbornMalePhenotypeRegistriesYoung Adult46,XY gonadal dysgenesisdifferences/disorders of sex developmentgonadectomysex reassignmentspontaneous pubertyvirilization

Identifiers

PMID40208111
PMCPMC12623043

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