title: Association between decreased klotho blood levels and organic growth hormone deficiency in children with growth impairment.
abstract: OBJECTIVE
  Klotho is an aging-modulating protein expressed mainly in the kidneys and choroid plexus, which can also be shed, released into the circulation and act as a hormone. Klotho deficient mice are smaller compared to their wild-type counterparts and their somatotropes show marked atrophy and reduced number of secretory granules. Recent data also indicated an association between klotho levels and growth hormone (GH) levels in acromegaly. We aimed to study the association between klotho levels and GH deficiency (GHD) in children with growth impairment.
  
  
  METHODS
  Prospective study comprising 99 children and adolescents (aged 9.0 ± 3.7 years, 49 male) undergoing GH stimulation tests for short stature (height-SDS = -2.1 ± 0.6). Klotho serum levels were measured using an α-klotho ELISA kit.
  
  
  RESULTS
  Klotho levels were significantly lower (p<0.001) among children with organic GHD (n = 11, 727 ± 273 pg/ml) compared to both GH sufficient participants (n = 59, 1497 ± 754 pg/ml) and those with idiopathic GHD (n = 29, 1645 ± 778 pg/ml). The difference between GHS children and children with idiopathic GHD was not significant. Klotho levels positively correlated with IGF-1- standard deviation scores (SDS) (R = 0.45, p<0.001), but were not associated with gender, pubertal status, age or anthropometric measurements.
  
  
  CONCLUSIONS
  We have shown, for the first time, an association between low serum klotho levels and organic GHD. If validated by additional studies, serum klotho may serve as novel biomarker of organic GHD.
authors.affiliation: Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Wolf
authors.affiliation: Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shiri
authors.initials: S
authors.lastname: Shahmoon
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Ben Ami
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Levy-Shraga
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: Kineret
authors.initials: K
authors.lastname: Mazor-Aronovitch
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Pinhas-Hamiel
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Yeshayahu
authors.affiliation: Institute of Endocrinology, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: Rina
authors.initials: R
authors.lastname: Hemi
authors.affiliation: Institute of Endocrinology, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: Hannah
authors.initials: H
authors.lastname: Kanety
authors.affiliation: Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Tami
authors.initials: T
authors.lastname: Rubinek
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: Dalit
authors.initials: D
authors.lastname: Modan-Moses
mesh_terms: D000293:Adolescent; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D005260:Female; D005966:Glucuronidase / Q000097:blood*; D048788:Growth and Development; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male
chemical_list: D019382:Human Growth Hormone; D005966:Glucuronidase; D000090265:Klotho Proteins