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

We report an unusual observation of a 3.8-yr-old boy with McCune-Albright s yndrome (MAS) associated with abnormal prepubertal testis enlargement and n o sexual precocity. Physical examination showed cafe-au-lait skin lesions, enlarged testes. prepubertal sized penis, and no pubic or axillary hair. Sk eletal radiography disclosed fibrous dysplasia. The serum testosterone leve l 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 pmo l/L (childhood range, 309-566), respectively. The LH response to a GnRH tes t was in the prepubertal range, whereas the FSH response was blunted. This abnormal hormone concentration profile indicates autonomous hyperfunction o f Sertoli cells, with no evidence of Leydig cell activation. Testicular his tology showed tubules with marked Sertoli cell hyperplasia and very rare ge rminal cells, and interstitial tissue containing mesenchymal cells but no m ature Leydig cells. DNA sequence analysis from bone and testis tissues dete cted the known activating mutation in MAS that results in replacement of Ar g by His at codon 201 of the G(s)alpha protein. Other endocrine tests showe d excessive GH secretion and moderate adrenal androgen hypersecretion. These findings are consistent with the occurrence of an activating mutation of the G(s)alpha gene mainly expressed in Sertoli cells and weakly express ed or absent in Leydig cells. Abnormal prepubertal testicular enlargement e xtends the clinical spectrum of MAS, suggesting that determination of serum inhibin B and anti-Mullerian hormone should be considered in boys with thi s syndrome. This observation demonstrates the usefulness of detailed molecu lar and biological investigations in atypical cases of MAS.