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Macroorchidism due to Autonomous Hyperfunction of Sertoli Cells and G_s Gene Mutation: An Unusual Expression of McCune-Albright Syndrome in a Prepubertal Boy

Département de Pédiatrie, Centre Hospitalier Universitaire (R.C., S.R., J.M.L.), 49000 Angers, France; Laboratoire d’Hormonologie, INSERM, U-439, Centre Hospitalier de l’Universite de Montpellier (S.L., C.S.), 34090 Montpellier, France, Unité de Recherches sur l’Endocrinologie du Développement, INSERM, U-493, Ecole Normale Supérieure (R.R.), 92120 Montrouge, France, Centro de Investigaciones Endocrinológicas, Hospital de Niños R. Gutiérrez (R.R., M.V.), 1425 Buenos Aires, Argentina; and Laboratoire d’Hormonologie, Hôpital Saint Vincent de Paul (N.L.), 75014 Paris, France

Address all correspondence and requests for reprints to: Dr. Régis Coutant, Department of Pediatrics, University Hospital, 4 rue Larrey, 49000 Angers, France. E-mail: recoutant{at}chu-angers.fr

We report an unusual observation of a 3.8-yr-old boy with McCune-Albright syndrome (MAS) associated with abnormal prepubertal testis enlargement and no sexual precocity. Physical examination showed café-au-lait skin lesions, enlarged testes, prepubertal sized penis, and no pubic or axillary hair. Skeletal radiography disclosed fibrous dysplasia. The serum testosterone level was 0.58 nmol/L and remained below 1.4 nmol/L during the 4-yr follow-up. By contrast, serum inhibin B and anti-Mullerian hormone concentrations were abnormally increased up to 255 pg/mL (childhood range, 35–180) and 792 pmol/L (childhood range, 309–566), respectively. The LH response to a GnRH test was in the prepubertal range, whereas the FSH response was blunted. This abnormal hormone concentration profile indicates autonomous hyperfunction of Sertoli cells, with no evidence of Leydig cell activation. Testicular histology showed tubules with marked Sertoli cell hyperplasia and very rare germinal cells, and interstitial tissue containing mesenchymal cells but no mature Leydig cells. DNA sequence analysis from bone and testis tissues detected the known activating mutation in MAS that results in replacement of Arg by His at codon 201 of the G_s protein. Other endocrine tests showed excessive GH secretion and moderate adrenal androgen hypersecretion.

These findings are consistent with the occurrence of an activating mutation of the G_s gene mainly expressed in Sertoli cells and weakly expressed or absent in Leydig cells. Abnormal prepubertal testicular enlargement extends the clinical spectrum of MAS, suggesting that determination of serum inhibin B and anti-Mullerian hormone should be considered in boys with this syndrome. This observation demonstrates the usefulness of detailed molecular and biological investigations in atypical cases of MAS.

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