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unilateral macroorchidism

Tuesday 20 April 2010

In boys, precocious activation of Leydig cell androgen secretion results in pubertal spermatogenesis, leading to testicular enlargement, and in the development of secondary sex characteristics.

Synopsis

- macro-orchidism

Etiology

- McCune-Albright syndrome (17101633, 16462147)

  • McCune-Albright syndrome (MAS), usually presenting with polyostotic bone dysplasia, cafĂ©-au-lait skin lesions and sexual precocity, results from a somatic activating mutation of the GNAS1 gene, which encodes the Gs-alpha protein involved in signalling of several G-protein-coupled receptors.
  • The clinical spectrum depends on tissue distribution of mutant-bearing cells.
  • Sexual precocity has been ascribed to the occurrence of a mutant GNAS1 allele in the gonadal anlage, from which all somatic cells of the differentiated gonads arise.
  • Sertoli cell hyperactivity
  • no signs of hyperandrogenism
  • However, sexual precocity is rare in MAS males while isolated testicular enlargement is frequently observed.
  • Gs-alpha (GNAS1) is functional in both Sertoli and Leydig cells.
  • The mutant GNAS1 allele can be present only in Sertoli cells, resulting in isolated Sertoli cell hyperfunction, evidenced by increased AMH expression and cell hyperplasia leading to prepubertal macro-orchidism, with no signs of Leydig cell activation.
  • The different early embryologic origin of precursors contributing to Sertoli and Leydig cell lineages may underlie the differential existence of the mutated GNAS1 gene.
  • Lack of occurrence of the mutation in Leydig cells may explain why sexual precocity is rarely observed in boys with MAS.

See also

- unilateral enlargement of the testis in childhood
- R201H-GNAS1 mutations
- bilateral macroorchidism in prepubertal boy

References

- Unexpected mosaicism of R201H-GNAS1 mutant-bearing cells in the testes underlie macro-orchidism without sexual precocity in McCune-Albright syndrome. Rey RA, Venara M, Coutant R, Trabut JB, Rouleau S, Lahlou N, Sultan C, Limal JM, Picard JY, Lumbroso S. Hum Mol Genet. 2006 Dec 15;15(24):3538-43. PMID: 17101633

- McCune-Albright syndrome in a boy may present with a monolateral macroorchidism as an early and isolated clinical manifestation. Arrigo T, Pirazzoli P, De Sanctis L, Leone O, Wasniewska M, Messina MF, De Luca F. Horm Res. 2006;65(3):114-9. PMID: 16462147

- Unilateral benign testicular macro-orchidism in a child: decisions and dilemmas. Henderson CG, Pohl H, Schwartz RH. Clin Pediatr (Phila). 2006 Oct;45(8):765-7. PMID: 16968963

- Macroorchidism due to autonomous hyperfunction of Sertoli cells and G(s)alpha gene mutation: an unusual expression of McCune-Albright syndrome in a prepubertal boy. Coutant R, Lumbroso S, Rey R, Lahlou N, Venara M, Rouleau S, Sultan C, Limal JM. J Clin Endocrinol Metab. 2001 Apr;86(4):1778-81. PMID: 11297617 (free) (bilateral macroorchidism in prepubertal boy)

- Unilateral enlargement of the testis in childhood: does it need exploration? MacMahon RA, Cussen LJ. J Pediatr Surg. 1991 Jan;26(1):68-9. PMID: 2005529