Skip to main content

Advertisement

SpringerLink
Log in

Management of Prepubertal Gynecomastia in Two Monozygotic Twins With Peutz-Jeghers Syndrome: From Aromatase Inhibitors To Subcutaneous Mastectomy

  • Original Article
  • Experimental/Special Topics
  • Published:
Aesthetic Plastic Surgery Aims and scope Submit manuscript

Abstract

Background

Prepubertal gynecomastia is characterized by the presence of palpable uni- or bilateral breast tissue in boys without other signs of sexual maturation. It may be the endocrine expression of rare syndromes such as Peutz-Jeghers syndrome (PJS). This study aimed to evaluate the effectiveness of anastrozole and to describe an innovative surgical approach.

Methods

This report presents twins with PJS, bilateral prepubertal gynecomastia, and testicular multifocal calcifications. Both twins were treated with anastrozole for 2 years. After finishing treatment, both were followed before subcutaneous mastectomy was performed by the “modified” Webster technique.

Results

Growth velocity decreased and gynecomastia diminished during anastrozole treatment. After discontinuation of therapy due to a sharp reduction in growth velocity, both twins showed regrowth of gynecomastia, with painful and strained breasts. A significant reduction in breast volume with glandular removal was achieved.

Conclusions

The findings of this study showed a multidisciplinary approach to prepubertal gynecomastia due to the synergy of pediatricians, radiologists, and plastic surgeons. The follow-up evaluation after the anastrozole treatment showed it to be an efficacious medical treatment, as an alternative to orchidectomy, to control the effects of circulating estrogens. Moreover, the results observed in the patients confirmed the validity and feasibility of the “modified” Webster technique in terms of aesthetic and functional results, patient satisfaction, and absence of complications.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Barros AC, Sampaio Mde C (2012) Gynecomastia: physiopathology, evaluation, and treatment. Sao Paulo Med J 130:187–197

    Article  PubMed  Google Scholar 

  2. Ma NS, Geffner ME (2008) Gynecomastia in prepubertal and pubertal men. Curr Opin Pediatr 20:465–470

    Article  PubMed  Google Scholar 

  3. Glass AR (1994) Gynecomastia. Endocrinol Metab Clin North Am 23:825–837

    PubMed  CAS  Google Scholar 

  4. Itami RM, Amundson GM, Kaplan SA, Lippe BM (1982) Prepubertal gynecomastia caused by an adrenal tumor. Diagnostic value of ultrasonography. Am J Dis Child 136:584–586

    PubMed  CAS  Google Scholar 

  5. Coen P, Kulin H, Ballantine T, Frauenhoffer E, Boal D, Inkster S, Brodie A, Santen R (1991) An aromatase-producing sex-cord tumor resulting in prepubertal gynecomastia. N Engl J Med 324:317–322

    Article  PubMed  CAS  Google Scholar 

  6. Berensztein E, Belgorosky A, de Davila MT, Rivarola MA (1995) Testicular steroid biosynthesis in a boy with a large cell calcifying Sertoli cell tumor producing prepubertal gynecomastia. Steroids 60:220–225

    Article  PubMed  CAS  Google Scholar 

  7. Hochberg Z, Even L, Zadik Z (1991) Mineralcorticoids in the mechanism of gynecomastia in adrenal hyperplasia caused by 11 beta-hydroxylase deficiency. J Pediatr 118:258–260

    Article  PubMed  CAS  Google Scholar 

  8. Wasniewska M, Arrigo T, Lombardo F, Crisafulli G, Salzano G, De Luca F (2009) 11-Hydroxylase deficiency as a cause of prepubertal gynecomastia. J Endocrinol Invest 32:387–388

    PubMed  CAS  Google Scholar 

  9. Gill K, Kirma N, Tekmal RR (2001) Overexpression of aromatase in transgenic male mice results in the induction of gynecomastia and other biochemical changes in mammary glands. J Steroid Biochem Mol Biol 77:13–18

    Article  PubMed  CAS  Google Scholar 

  10. Irahara N, Miyoshi Y, Taguchi T, Tamaki Y, Noguchi S, Harada N (2005) Possible involvement of aromatase overexpression induced by cyclo-oxygenase-2 in the pathogenesis of idiopathic gynecomastia. Endocr Res 31:219–227

    Article  PubMed  CAS  Google Scholar 

  11. Deepinder F, Braunstein GD (2012) Drug-induced gynecomastia: an evidence-based review. Expert Opin Drug Saf 11:779–795

    Article  PubMed  CAS  Google Scholar 

  12. Bowman JD, Kim H, Bustamante JJ (2012) Drug-induced gynecomastia. Pharmacotherapy 32:1123–1140

    Article  PubMed  CAS  Google Scholar 

  13. Amos Cl, Bali D, Thiel TJ, Anderson JP, Gourley I, Frazier ML, Lynch PM, Luchtefeld MA, Young A, McGarrity TJ, Seldin MF (1997) Fine mapping of a genetic locus for Peutz-Jeghers syndrome on chromosome 19p. Cancer Res 57:3653–3656

    PubMed  CAS  Google Scholar 

  14. Hemminki A, Tomlinson I, Markie D, Järvinen H, Sistonen P, Björkqvist AM, Knuutila S, Salovaara R, Bodmer W, Shibata D, de la Chapelle A, Aaltonen LA (1997) Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nat Genet 15:87–90

    Article  PubMed  CAS  Google Scholar 

  15. Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Müller O, Back W, Zimmer M (1998) Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18:38–43

    Article  PubMed  CAS  Google Scholar 

  16. Jiang CY, Esufali S, Berk T, Gallinger S, Cohen Z, Tobi M, Redston M, Bapat B (1999) STK11/LKB1 germline mutations are not identified in most Peutz-Jeghers syndrome patients. Clin Genet 56:136–141

    Article  PubMed  CAS  Google Scholar 

  17. Giardiello FM, Trimbath JD (2006) Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 4:408–415

    Article  PubMed  Google Scholar 

  18. Bulun SE, Noble LS, Takayama K, Michael MD, Agarwal V, Fisher C, Zhao Y, Hinshelwood MM, Ito Y, Simpson ER (1997) Endocrine disorders associated with inappropriately high aromatase expression. J Steroid Biochem Mol Biol 61:133–139

    Article  PubMed  CAS  Google Scholar 

  19. Cantú JM, Rivera H, Ocampo-Campos R, Bedolla N, Cortés-Gallegos V, González-Mendoza A, Díaz M, Hernández A (1980) Peutz-Jeghers syndrome with feminizing sertoli cell tumor. Cancer 46:223–228

    Article  PubMed  Google Scholar 

  20. Lefevre H, Bouvattier C, Lahlou N, Adamsbaum C, Bougnères P, Carel JC (2006) Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor. Eur J Endocrinol 154:221–227

    Article  PubMed  CAS  Google Scholar 

  21. Alikasifoglu A, Gonc EN, Akcoren Z, Kale G, Ciftci AO, Senocak ME, Yordam N (2002) Feminizing Sertoli cell tumor associated with Peutz-Jeghers syndrome. J Pediatr Endocrinol Metab 15:449–452

    Article  PubMed  Google Scholar 

  22. Grandone A, del Giudice EM, Cirillo G, Santarpia M, Coppola F, Perrone L (2011) Prepubertal gynecomastia in two monozygotic twins with Peutz-Jeghers syndrome: two years’ treatment with anastrozole and genetic study. Horm Res Paediatr 75:374–379

    Article  PubMed  CAS  Google Scholar 

  23. Webster JP (1946) Mastectomy for gynecomastia through a semicircular intra-areolar incision. Ann Surg 124:557–575

    Article  Google Scholar 

  24. Einav-Bachar R, Phillip M, Aurbach-Klipper Y, Lazar L (2004) Prepubertal gynaecomastia: aetiology, course and outcome. Clin Endocrinol Oxford 61:55–60

    Article  CAS  Google Scholar 

  25. Brodie A, Long B (2001) Aromatase inhibition and inactivation. Clin Cancer Res 7:4343s–4349s

    PubMed  CAS  Google Scholar 

  26. Brodie A, Lu Q, Nakamura J (1997) Aromatase in the normal breast and breast cancer. J Steroid Biochem Mol Biol 61:281–286

    Article  PubMed  CAS  Google Scholar 

  27. Hertl MC, Wiebel J, Schäfer H, Willig HP, Lambrecht W (1998) Feminizing sertoli cell tumors associated with Peutz-Jeghers syndrome: an increasingly recognized cause of prepubertal gynecomastia. Plast Reconstr Surg 102:1151–1157

    PubMed  CAS  Google Scholar 

  28. Braunstein GD (1993) Gynecomastia. N Engl J Med 328:490–495

    Article  PubMed  CAS  Google Scholar 

  29. Laguna MP, Pizzocaro G, Klepp O, Algaba F, Kisbenedek L, Leiva O, EAU Working Group on Oncological Urology (2001) EAU guidelines on testicular cancer. Eur Urol 40:102–110

    Article  PubMed  CAS  Google Scholar 

  30. Viatori M (2012) Testicular cancer. Semin Oncol Nurs 28:180–189

    Article  PubMed  Google Scholar 

  31. Daniels IR, Layer GT (2003) Testicular tumours presenting as gynaecomastia. Eur J Surg Oncol 29:437–439

    Article  PubMed  CAS  Google Scholar 

  32. Foppiani L, Bernasconi D, Del Monte P, Marugo A, Toncini C, Marugo M (2005) Leydig cell tumour-induced bilateral gynaecomastia in a young man: endocrine abnormalities. Andrologia 37:36–39

    Article  PubMed  CAS  Google Scholar 

  33. Zarrilli S, Lombardi G, Paesano L, Di Somma C, Colao A, Mirone V, De Rosa M (2002) Hormonal and seminal evaluation of Leydig cell tumour patients before and after orchiectomy. Andrologia 32:147–154

    Google Scholar 

  34. Solh HM, Azoury RS, Najjar SS (1983) Peutz-Jeghers syndrome associated with precocious puberty. J Pediatr 103:593–595

    Article  PubMed  CAS  Google Scholar 

  35. Kara C, Kutlu AO, Tosun MS, Apaydin S, Senel F (2005) Sertoli cell tumor causing prepubertal gynecomastia in a boy with Peutz-Jeghers syndrome: the outcome of 1-year treatment with the aromatase inhibitor testolactone. Horm Res 63:252–256

    Article  PubMed  CAS  Google Scholar 

  36. Gourgari E, Saloustros E, Stratakis CA (2012) Large-cell calcifying Sertoli cell tumors of the testes in pediatrics. Curr Opin Pediatr 24:518–522

    Article  PubMed  Google Scholar 

  37. Devalia HL, Layer GT (2009) Current concepts in gynaecomastia. Surgeon 7:114–119

    Article  PubMed  CAS  Google Scholar 

  38. Saad MN, Kay S (1984) The circumareolar incision: a useful incision for gynaecomastia. Ann R Coll Surg Engl 66:121–122

    PubMed  CAS  Google Scholar 

  39. Pitanguy I (1966) Transareolar incision for gynecomastia. Plast Reconstr Surg 38:414–419

    Article  PubMed  CAS  Google Scholar 

  40. Kasielska A, Antoszewski B (2012) Surgical management of gynecomastia: an outcome analysis. Ann Plast Surg (in press)

Download references

Acknowledgments

The authors thank Prof. Giuseppina Caraglia for his technical support and for reviewing the manuscript in English.

Author information

Authors and Affiliations

  1. Department of Orthopedic, Traumatologic, Rehabilitative, and Plastic-Reconstructive Sciences, Second University of Naples, L. Miraglia Square 2, 80138, Naples, Italy

    Giuseppe Andrea Ferraro, Francesco De Francesco, Francesco D’Andrea, Chiara Cataldo & Gianfranco Nicoletti

  2. Department of Pediatrics “F. Fede”, Second University of Naples, Naples, Italy

    Tiziana Romano, Anna Grandone, Emanuele Miraglia del Giudice & Laura Perrone

  3. Department of Clinical and Experimental Medicine “F. Magrassi, A. Lanzara”, Section of Radiology and Radiotherapy, Second University of Naples, Naples, Italy

    Gianluca Gatta & Graziella Di Grezia

Authors
  1. Giuseppe Andrea Ferraro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiziana Romano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesco De Francesco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Grandone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesco D’Andrea
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emanuele Miraglia del Giudice
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chiara Cataldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gianluca Gatta
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Graziella Di Grezia
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Laura Perrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gianfranco Nicoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuseppe Andrea Ferraro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferraro, G.A., Romano, T., De Francesco, F. et al. Management of Prepubertal Gynecomastia in Two Monozygotic Twins With Peutz-Jeghers Syndrome: From Aromatase Inhibitors To Subcutaneous Mastectomy. Aesth Plast Surg 37, 1012–1022 (2013). https://doi.org/10.1007/s00266-013-0188-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00266-013-0188-z

Keywords

Search

Navigation