Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor.

BACKGROUND Peutz-Jeghers syndrome (PJS) is a rare autosomal-dominant disorder characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation and increased predisposition to various neoplasms. Endocrine manifestations in PJS include gynecomastia due to calcified Sertoli cell testicular tumors usually referred to as large-cell calcifying Sertoli cell tumors (LSCT). OBJECTIVE To evaluate the value of endocrine markers and aromatase inhibitor treatment in children with PJS and LSCT. DESIGN AND SETTING Familial cases, followed in a tertiary care center. PATIENTS Two male siblings aged 7 and 9 years with PJS and LSCT. INTERVENTION Third generation aromatase inhibitor (anastrozole) in one of the patients. MAIN OUTCOME MEASURES Longitudinal measurements of sex-steroids, gonadotropins, Sertoli cell markers and auxological evaluation. RESULTS The two male siblings with PJS had similar bilateral multifocal testicular calcifications and biochemical evidence of Sertoli cell dysfunction manifested by elevated plasma inhibin-alpha levels. Only one sibling had gynecomastia. Estradiol levels were normal in both. During treatment with anastrozole, estradiol levels, growth and skeletal maturation, as well as Sertoli cell markers (inhibin B, inhibin-alpha and anti-Mullerian hormone) decreased. CONCLUSIONS Inhibin-alpha may be considered as a marker for LSCT in children with PJS, pointing to a specific defect in inhibin regulation in this condition. Moreover, the decrease in Sertoli cell markers during aromatase inhibitor treatment suggests that increased estrogen production is a primary event regulating downstream production of Sertoli cell peptides. Anastrozole is efficient in controlling the clinical features of the disease and should be proposed as an alternative to bilateral orchidectomy, which is often performed in this condition.