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17β-Hydroxysteroid dehydrogenase-3 deficiency: From pregnancy to adolescence

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Abstract

Objective: Aim of this study is to report on basal clinical phenotype and follow up after diagnosis, of patients with 17β-hydroxysteroid-dehydrogenase type 3 (17β-HSD3) deficiency in Italy. Setting: Pediatric Endocrine Departments, University Hospitals. Patients: The cases of 5 Italian subjects affected by 17β-HSD3 deficiency are presented in this study. Interventions: Laboratory and genetic assessment. Gonadectomy and female sex assignment (4 patients) or GnRH analog therapy to regress puberty and gender identity disorder (1 patient). Results: Presentation lasted from pregnancy (pre-natal diagnosis of a 46,XY fetus with female external genitalia) to infancy (inguinal hernia containing testes/clitoromegaly) and adolescence (virilisation). All subjects but one (subject 1, Central-Northern Italy) were from small areas of Southern Italy. Endocrine data (baseline and/or stimulated testosterone/A4-androstenedione ratio) were informative. Two girls were homozygous for 17β-HSD3 gene mutations (G289S/G289S; R80W/R80W), while the others were compound heterozygous (IVS325+4 A>T/A203V; L212Q/M235V; R80W/A235E). Four patients were confirmed as females and were well-adjusted with assigned sex; gender identity disorder improved during treatment with GnRH analog in the last subject. Conclusions: 17βHSD3 deficiency may present from pregnancy to puberty for different clinical issues. Albeit testosterone/A4-androstenedione ratio represents the most accurate endocrine marker to diagnose the disorder, hCG-stimulation is mandatory in pre-puberty. Molecular analysis of 17β-HSD3 gene should be performed to confirm the diagnosis. Temporary GnRH analog treatment may regress gender identity disorder and provide time to confirm or change the birth sex assignment. Female individuals seems to be compliant with their sex, providing that virilisation does not occur. In Italy, the disorder seems to be more prevalent in the Southern regions and shows genetic heterogeneity.

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References

  1. Hughes IA, Houk C, Ahmed SF, Lee PA; LWPES Consensus Group; ESPE Consensus Group. Consensus statement on management of intersex disorders. Arch Dis Child 2006, 91: 554–63.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Faienza MF, Giordani L, Delvecchio M, Cavallo L. Clinical, endocrine, and molecular findings in 17beta-hydroxysteroid dehydrogenase type 3 deficiency. J Endocrinol Invest 2008, 31: 85–91.

    Article  PubMed  CAS  Google Scholar 

  3. Bertelloni S, Dati E, Hiort O. Diagnosis of 17β-hydroxysteroid dehydrogenase deficiency: a review. Expert Review Endocrinol Metab 2009, 4: 53–65.

    Article  CAS  Google Scholar 

  4. Geissler WM, Davis DL, Wu L, et al. Male pseudohermaphroditism caused by mutations of testicular 17beta-hydroxysteroid dehydrogenase 3. Nat Genet 1994, 7: 34–9.

    Article  PubMed  CAS  Google Scholar 

  5. Andersson S, Geissler WM, Wu L, et al. Molecular genetics and pathophysiology of 17beta-hydroxysteroid dehydrogenase 3 deficiency. J Clin Endocrinol Metab 1996, 81: 130–6.

    PubMed  CAS  Google Scholar 

  6. Mendonca BB, Inacio M, Arnhold IJ, et al. Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management. Medicine (Baltimore) 2000, 79: 299–309.

    Article  CAS  Google Scholar 

  7. Lee YS, Kirk JM, Stanhope RG, et al. Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Clin Endocrinol (Oxf) 2007, 67: 20–8.

    Article  CAS  Google Scholar 

  8. Sinnecker GH, Hiort O, Dibbelt L, et al. Phenotypic classification of male pseudohermaphroditism due to steroid 5alpha-reductase 2 deficiency. Am J Med Genet 1996, 63: 223–30.

    Article  PubMed  CAS  Google Scholar 

  9. Cacciari E, Milani S, Balsamo A, et al. Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest 2006, 29: 581–93.

    Article  PubMed  CAS  Google Scholar 

  10. Sane K, Pescovitz OH. The clitoral index: a determination of clitoral size in normal girls and in girls with abnormal sexual development. J Pediat 1992, 120: 264–6.

    Article  PubMed  CAS  Google Scholar 

  11. Boehmer ALM, Brinkmann AO, Sandkuijl LA, et al. 17beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics and worldwide distribution of ancient and de novo mutations. J Clin Endocrinol Metab 1999, 84: 4713–21.

    PubMed  CAS  Google Scholar 

  12. Twesten W, Holterhus P, Sippell WG, et al. Clinical, endocrine, and molecular genetic findings in patients with 17beta-hydroxysteroid dehydrogenase deficiency. Horm Res 2000, 53: 26–31.

    Article  PubMed  CAS  Google Scholar 

  13. Crofton PM, Evans AE, Groome NP, Taylor MR, Holland CV, Kelnar CJ. Inhibin B in boys from birth to adulthood: relationship with age, pubertal stage, FSH and testosterone. Clin Endocrinol (Oxf) 2002, 56: 215–21.

    Article  CAS  Google Scholar 

  14. Moghrabi N, Hughes IA, Dunaif A, Andersson S. Deleterious mis-sense mutations and silent polymorphism in the human 17β-hydroxysteroid dehydrogenase 3 gene (HSD17β3). J Clin Endocrinol Metab 1998, 83: 2855–60.

    PubMed  CAS  Google Scholar 

  15. Cassorla FG, Golden SM, Johnsonbaugh RE, Heroman WM, Loriaux DL, Sherins RJ. Testicular volume during early infancy. J Pediatr 1981, 99: 742–3.

    Article  PubMed  CAS  Google Scholar 

  16. Taranger J, Engström I, Lichtenstein H, Svennberg-Redegren I. VI. Somatic pubertal development. Acta Paediatr Scand Suppl 1976, 258: 121–35.

    Article  PubMed  Google Scholar 

  17. Parisi MA, Ramsdell LA, Burns MW, et al. A Gender Assessment Team: experience with 250 patients over a period of 25 years. Genet Med 2007, 9: 348–57.

    Article  PubMed  Google Scholar 

  18. 18. Hughes IA. Disorders of sex development: a new definition and classification. Best Pract Res Clin Endocrinol Metab 2008, 22: 119–34.

    Article  PubMed  Google Scholar 

  19. Rosler A. Steroid 17[beta]-hydroxysteroid dehydrogenase deficiency in man: An inherited form of male pseudohermaphroditism. J Steroid Biochem Mol Biol 1992, 43: 989–1002.

    Article  PubMed  CAS  Google Scholar 

  20. Balducci R, Toscano V, Wright F, et al. Familial male pseudohermaphroditism with gynaecomastia due to 17beta-hydroxysteroid dehydrogenase deficiency. A report of 3 cases. Clin Endocrinol (Oxf) 1985, 23: 439–44.

    Article  CAS  Google Scholar 

  21. Latronico AC, Arnhold IJ. Inactivating mutations of LH and FSH receptors — from genotype to phenotype. Pediatr Endocrinol Rev 2006, 4: 28–31.

    PubMed  Google Scholar 

  22. Yalinkaya A, Yayla M, Erdemoglu M. Prenatal diagnosis of a fetus with androgen insensitivity syndrome (AIS). Prenat Diagn 2007, 27: 856–7.

    Article  PubMed  Google Scholar 

  23. Andersson AM. Inhibin B in the assessment of seminiferous tubular function. Baillieres Best Pract Res Clin Endocrinol Metab 2000, 14: 389–97.

    Article  PubMed  CAS  Google Scholar 

  24. Bilbao JR, Loridan L, Audì L, Gonzalo E, Castaño L. A novel mis-sense (R80W mutation in 17β-hydroxysteroid dehydrogenase type 3 gene associated with male pseudohermaphroditism. Eur J Endocrinol 1998, 139: 330–3.

    Article  PubMed  CAS  Google Scholar 

  25. Rashid HH, Cos LR, Weinberg E, Messing EM. Testicular microlithiasis: a review and its association with testicular cancer. Urol Oncol 2004, 22: 285–9.

    Article  PubMed  Google Scholar 

  26. Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH. Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev 2006, 27: 468–84.

    Article  PubMed  CAS  Google Scholar 

  27. Mains LM, Vakili B, Lacassie Y, Andersson S, Lindqvist A, Rock JA. 17β-hydroxysteroid dehydrogenase 3 deficiency in a male pseudohermaphrodite. Fertil Steril 2008, 89: 228.e13-17.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Margiotti K, Kim E, Pearce CL, Spera E, Novelli G, Reichardt JK. Association of the G289S single nucleotide polymorphism in the HSD17B3 gene with prostate cancer in Italian men. Prostate 2002, 53: 65–8.

    Article  PubMed  CAS  Google Scholar 

  29. Cohen-Kettenis PT. Gender change in 46,XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav 2005, 34: 399–410.

    Article  PubMed  Google Scholar 

  30. Hiort O, Reinecke S, Thyen U, et al. Puberty in disorders of somatosexual differentiation. J Pediatr Endocrinol Metab 2003, 16: 297–306.

    PubMed  CAS  Google Scholar 

  31. Cohen-Kettenis PT, Delemarre-van de Waal HA, Gooren LJ. The Treatment of Adolescent Transsexuals: Changing Insights. J Sex Med 2008, 5: 1892–7.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Adolescent Medicine, Department of Reproductive Medicine and Paediatrics, Santa Chiara University Hospital, Pisa, Italy

    S. Bertelloni MD & G. I. Baroncelli

  2. Department of Gynecologic, Obstetric and Pediatric Sciences, University of Bologna, Bologna, Italy

    A. Balsamo, M. Gennari, A. Nicoletti & A. Cicognani

  3. Department of Biomedicine of the Developmental Age, University of Bari, Bari, Italy

    L. Giordani, M. Delvecchio, L. Cavallo & M. F. Faienza

  4. Perdiatric Endocrinology, Pediatric Hospital “Giovanni XXIII”, Bari, Italy

    R. Fischetto

  5. Department of Paediatrics and Adolescent Medicine, University “Vita e Salute”, San Raffaele Hospital, Milan, Italy

    G. Russo & G. Chiumello

  6. Maternal and child Health Department, University of Palermo, Palermo, Italy

    M. C. Maggio

  7. Department of Pediatrics, University of Magna Grecia, Catanzaro, Italy

    D. Concolino

  8. Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Lubeck, Lubeck, Germany

    O. Hiort

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  1. S. Bertelloni MD
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  2. A. Balsamo
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Correspondence to S. Bertelloni MD.

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Bertelloni, S., Balsamo, A., Giordani, L. et al. 17β-Hydroxysteroid dehydrogenase-3 deficiency: From pregnancy to adolescence. J Endocrinol Invest 32, 666–670 (2009). https://doi.org/10.1007/BF03345738

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