title: A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy.
abstract: Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.
authors.affiliation: Pós-Graduação em Ciências da Saúde, Centro de Ciências da Saúde, Universidade Estadual de Londrina (UEL), Londrina, PR, Brasil.
authors.forename: Natasha G
authors.initials: NG
authors.lastname: Ludwig
authors.affiliation: Serviço de Endocrinologia do Hospital Universitário, UEL, Londrina, PR, Brasil.
authors.forename: Rafael F
authors.initials: RF
authors.lastname: Radaeli
authors.affiliation: Serviço de Endocrinologia do Hospital Universitário, UEL, Londrina, PR, Brasil.
authors.forename: Mariana M X
authors.initials: MM
authors.lastname: Silva
authors.affiliation: Serviço de Endocrinologia do Hospital Universitário, UEL, Londrina, PR, Brasil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Romero
authors.affiliation: Pós-Graduação em Ciências da Saúde, Centro de Ciências da Saúde, Universidade Estadual de Londrina (UEL), Londrina, PR, Brasil.|Serviço de Endocrinologia do Hospital Universitário, UEL, Londrina, PR, Brasil.
authors.forename: Alexandre J F
authors.initials: AJ
authors.lastname: Carrilho
authors.affiliation: Laboratório de Hormônios e Genética Molecular (LIM/42), Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, SP, Brasil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Bessa
authors.affiliation: Laboratório de Hormônios e Genética Molecular (LIM/42), Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, SP, Brasil.
authors.forename: Delanie B
authors.initials: DB
authors.lastname: Macedo
authors.affiliation: Serviço de Endocrinologia do Hospital Universitário, UEL, Londrina, PR, Brasil.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Oliveira
authors.affiliation: Laboratório de Hormônios e Genética Molecular (LIM/42), Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, SP, Brasil.
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
authors.affiliation: Pós-Graduação em Ciências da Saúde, Centro de Ciências da Saúde, Universidade Estadual de Londrina (UEL), Londrina, PR, Brasil.|Serviço de Endocrinologia do Hospital Universitário, UEL, Londrina, PR, Brasil.
authors.forename: Tânia L
authors.initials: TL
authors.lastname: Mazzuco
mesh_terms: D002648:Child; D019175:DNA Methylation; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy / Q000379:methods; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011218:Prader-Willi Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011629:Puberty, Precocious / Q000150:complications / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone