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Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement

  • Arjun Baidya , Asish Kumar Basu , Rana Bhattacharjee ORCID logo , Dibakar Biswas , Kaushik Biswas , Partha Pratim Chakraborty ORCID logo EMAIL logo , Purushottam Chatterjee , Subhankar Chowdhury , Ranen Dasgupta , Amritava Ghosh ORCID logo , Sujoy Ghosh ORCID logo , Debasis Giri , Soumik Goswami ORCID logo , Indira Maisnam ORCID logo , Animesh Maiti , Sunetra Mondal , Pradip Mukhopadhyay ORCID logo , Sarmishtha Mukhopadhyay , Satinath Mukhopadhyay ORCID logo , Salil Kumar Pal , Kaushik Pandit , Sayantan Ray ORCID logo , Bibek Roy Chowdhury , Moutusi Raychaudhuri , Pradip Raychaudhuri , Ajitesh Roy , Pranab Kumar Sahana , Debmalya Sanyal , Trinanjan Sanyal , Ravi Kant Saraogi , Dasarathi Sarkar , Nilanjan Sengupta , Awadhesh Kumar Singh ORCID logo and Anirban Sinha
Published/Copyright: November 25, 2022
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 36 Issue 1

Abstract

Objectives

46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis.

Content

The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members.

Summary

The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings.

Outlook

The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Keywords: 17β-hydroxysteroid dehydrogenase 3 deficiency; 3β-hydroxysteroid dehydrogenase 2 deficiency; 5ɑ-reductase 2 deficiency; 46, XY DSD; androgen insensitivity syndrome; ambiguous genitalia
Corresponding author: Dr. Partha Pratim Chakraborty, MBBS, MD, DM (Endo), DNB (Endo), FACE, FICP, Assistant Professor, Department of Endocrinology & Metabolism, Medical College & Hospital, Kolkata, India, E-mail:

  1. Research funding: Not applicable.

  2. Author contributions: The name of the authors have been listed as per alphabetical order of their surnames. First draft was written by Sunetra Mondal and Sayantan Ray. The final draft was written by Partha Pratim Chakraborty, Rana Bhattacharjee and Ajitesh Roy. Partha Pratim Chakraborty and Rana Bhattacharjee responded to the reviewers’ comments. All the authors discussed the draft, provided their scientific inputs during discussion and approved the final draft before submission. All authors have accepted responsibility for the entire content of the manuscript and approved the author list.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

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Received: 2022-05-30
Accepted: 2022-10-31
Published Online: 2022-11-25
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Disorders of sex development – biologic, genetic, cultural, societal, and psychologic diversity of the human nature
  4. Review
  5. Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement
  6. Original Articles
  7. Penile diameter during puberty in boys: a retrospective analysis of longitudinally obtained data
  8. Evaluation of bladder dysfunction in children and adolescents with type 1 diabetes mellitus by uroflowmetry
  9. All aspects of galactosemia: a single center experience
  10. The evolution of pituitary cysts in growth hormone-treated children
  11. Phototherapy-induced hypocalcemia and hypoparathyroidism in icteric term newborns
  12. Clinical and laboratory evaluation of children with congenital hyperinsulinism: a single center experience
  13. Does cystatin C have an immunomodulatory role in Hashimoto’s thyroiditis?
  14. Molecular genetic etiology by whole exome sequence analysis in cases with familial type 1 diabetes mellitus without HLA haplotype predisposition or incomplete predisposition
  15. Features of BSCL2 related congenital generalized lipodystrophy in China: long-term follow-up of three patients and literature review
  16. Case Reports
  17. Congenital adrenal hyperplasia with a CYP21A2 deletion overlapping the tenascin-X gene: an atypical presentation
  18. The smallest dislocated microduplication of Xq27.1 harboring SOX3 gene associated with XX male phenotype
  19. Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report
  20. Human chorionic gonadotrophin secreting adrenocortical neoplasm presenting with peripheral precocious puberty in an infant
  21. Atypical familial diabetes associated with a novel NEUROD1 nonsense variant
https://doi.org/10.1515/jpem-2022-0515
Keywords for this article
17β-hydroxysteroid dehydrogenase 3 deficiency; 3β-hydroxysteroid dehydrogenase 2 deficiency; 5ɑ-reductase 2 deficiency; 46, XY DSD; androgen insensitivity syndrome; ambiguous genitalia

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Disorders of sex development – biologic, genetic, cultural, societal, and psychologic diversity of the human nature
  4. Review
  5. Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement
  6. Original Articles
  7. Penile diameter during puberty in boys: a retrospective analysis of longitudinally obtained data
  8. Evaluation of bladder dysfunction in children and adolescents with type 1 diabetes mellitus by uroflowmetry
  9. All aspects of galactosemia: a single center experience
  10. The evolution of pituitary cysts in growth hormone-treated children
  11. Phototherapy-induced hypocalcemia and hypoparathyroidism in icteric term newborns
  12. Clinical and laboratory evaluation of children with congenital hyperinsulinism: a single center experience
  13. Does cystatin C have an immunomodulatory role in Hashimoto’s thyroiditis?
  14. Molecular genetic etiology by whole exome sequence analysis in cases with familial type 1 diabetes mellitus without HLA haplotype predisposition or incomplete predisposition
  15. Features of BSCL2 related congenital generalized lipodystrophy in China: long-term follow-up of three patients and literature review
  16. Case Reports
  17. Congenital adrenal hyperplasia with a CYP21A2 deletion overlapping the tenascin-X gene: an atypical presentation
  18. The smallest dislocated microduplication of Xq27.1 harboring SOX3 gene associated with XX male phenotype
  19. Rare PHEX intron variant causes complete and severe phenotype in a family with hypophosphatemic rickets: a case report
  20. Human chorionic gonadotrophin secreting adrenocortical neoplasm presenting with peripheral precocious puberty in an infant
  21. Atypical familial diabetes associated with a novel NEUROD1 nonsense variant
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