title: Blunted response to a growth hormone stimulation test is associated with unfavorable cardiovascular risk factor profile in childhood cancer survivors.
abstract: BACKGROUND
  Childhood cancer survivors (CCS) are at risk for growth hormone (GH) deficiency. CCS are also at increased risk for early mortality from cardiovascular (CV) disease, but the association between GH levels and CV risk remains poorly understood. The goal of this study was to examine the cross-sectional association between stimulated GH levels and CV risk factors in CCS younger than 18 years.
  
  
  METHODS
  A total of 276 CCS (147 males, 14.4 ± 2.6 years) ≥5 years after cancer diagnosis, and 208 sibling controls (112 males, 13.6 ± 2.4 years) participated in this cross-sectional study, which included anthropometry, body composition, and metabolic studies. Blunted response (BR) was defined as peak GH level <7 µg/L after clonidine and arginine. Insulin sensitivity (M(lbm) ) was measured by euglycemic hyperinsulinemic clamp. Statistical analyses used linear and logistic regression accounting for sibling clustering, adjusted for age, sex, Tanner stage, and adiposity.
  
  
  RESULTS
  Thirty-four (12%) CCS showed BR to GH stimulation. BR CCS were shorter and had a lower IGF-1 than controls; only 6 of 34 received cranial radiation therapy. CCS with normal stimulated GH response were similar to controls for CV risk factors. Conversely, BR CCS had greater adiposity, higher lipids, and lower M(lbm) than controls. Differences in lipids and M(lbm) between BR CCS and controls remained significant after adjustment for BMI or visceral fat.
  
  
  CONCLUSIONS
  BR to GH stimulation is prevalent in CCS youth and is associated with an unfavorable CV risk factor profile. Further studies are needed to establish the mechanisms of these associations.
authors.affiliation: Pediatric Endocrinology, University of Minnesota Amplatz Children's Hospital, Minneapolis, Minnesota 55454, USA. petry005@umn.edu
authors.forename: Anna
authors.initials: A
authors.lastname: Petryk
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
authors.forename: Brigitte
authors.initials: B
authors.lastname: Frohnert
authors.forename: Antoinette
authors.initials: A
authors.lastname: Moran
authors.forename: Lisa
authors.initials: L
authors.lastname: Chow
authors.forename: Alan R
authors.initials: AR
authors.lastname: Sinaiko
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Steffen
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Perkins
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: James S
authors.initials: JS
authors.lastname: Hodges
authors.forename: Julia
authors.initials: J
authors.lastname: Steinberger
mesh_terms: D050154:Adiposity / Q000502:physiology; D000293:Adolescent; D002318:Cardiovascular Diseases / Q000150:complications* / Q000378:metabolism; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D009369:Neoplasms / Q000150:complications*; D012307:Risk Factors; D017741:Survivors
chemical_list: D019382:Human Growth Hormone