title: Prepubertal gynecomastia in two monozygotic twins with Peutz-Jeghers syndrome: two years' treatment with anastrozole and genetic study.
abstract: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous pigmentation and increased predisposition to neoplasms. Endocrine manifestations in PJS include gynecomastia and advanced bone age due to estrogen production by large-cell calcifying Sertoli cell tumors (LSCT). We present two 9-year-old male monozygotic twins, with PJS, bilateral progressive prepubertal gynecomastia and testicular bilateral multifocal calcifications, suggesting a diagnosis of LSCT. Their father had PJS but no history of gynecomastia or testicular calcifications. No mutations were found in the tumor suppressor gene LKB1/STK11, which is responsible for about 60% of PJS cases. The genotype of the aromatase cytochrome P450 19, a key enzyme involved in estrogen biosynthesis, was the same in the father and his twins. To reduce gynecomastia and delay skeletal maturation, the children started treatment with anastrozole, an aromatase inhibitor. Growth velocity decreased and gynecomastia diminished. After 2 years of treatment, anastrozole is still currently used at a dosage of 1 mg once daily with no side effects. In this study, a couple of monozygotic twins with PJS, prepubertal gynecomastia and LSCT is reported for the first time and anastrozole appears to be an efficacious medical treatment, as an alternative to orchidectomy, to control the effects of estrogen excess.
authors.affiliation: Department of Pediatrics F. Fede, Seconda Università degli Studi di Napoli, Naples, Italy. agrandone@gmail.com
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.forename: Emanuele Miraglia
authors.initials: EM
authors.lastname: del Giudice
authors.forename: Grazia
authors.initials: G
authors.lastname: Cirillo
authors.forename: Michele
authors.initials: M
authors.lastname: Santarpia
authors.forename: Filomena
authors.initials: F
authors.lastname: Coppola
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
mesh_terms: D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D002648:Child; D004200:Diseases in Twins / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D005823:Genetics; D006177:Gynecomastia / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D010580:Peutz-Jeghers Syndrome / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D011627:Puberty / Q000502:physiology; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014230:Triazoles / Q000627:therapeutic use*; D014430:Twins, Monozygotic
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole