title: Phenotypic analysis and growth response to different growth hormone treatment schedules in two siblings with an inactivating mutation in the growth hormone-releasing hormone receptor gene.
abstract: Mutations in the GHRH receptor (GHRHR) gene (GHRHR) are emerging as a common cause of familial isolated growth hormone deficiency (IGHD) type IB. The use of gonadotropin-releasing hormone (GnRH) analogues has been advocated as a tool to delay puberty in patients with isolated GH deficiency (IGHD), allowing longer time for the beneficial effect of exogenous human GH (hGH) treatment on growth. We describe two male siblings with IGHD due to a homozygous missense GHRHR mutation who, because they were started on hGH therapy at different ages, presented with different height SDS at the onset of puberty and therefore had different predicted target heights. The shorter brother was treated with GnRH analogue plus hGH for 3 years, whereas the other brother received only hGH. Despite different predicted heights at the onset of puberty, they attained similar final heights. We conclude that in patients with IGHD, GnRH analogue treatment should be considered to delay puberty and obtain a maximal growth response if hGH treatment is started in late childhood and the predicted height at puberty onset is below the genetic target.
authors.affiliation: Pediatric Endocrinology Unit, Virgen de las Nieves Hospital, Granada, Spain. respigares@wanadoo.es
authors.forename: R
authors.initials: R
authors.lastname: Espigares
authors.forename: I
authors.initials: I
authors.lastname: Martín de Lara
authors.forename: F
authors.initials: F
authors.lastname: Ruiz-Cabello
authors.forename: L
authors.initials: L
authors.lastname: Ortega
authors.forename: A
authors.initials: A
authors.lastname: Ferrández Longás
authors.forename: J
authors.initials: J
authors.lastname: Argente
authors.forename: R
authors.initials: R
authors.lastname: Salvatori
mesh_terms: D000293:Adolescent; D001827:Body Height / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D035781:Siblings; D016896:Treatment Outcome
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor