title: Growth hormone deficiency after childhood bone marrow transplantation with total body irradiation: interaction with adiposity and age.
abstract: OBJECTIVE
  Bone marrow transplantation with total body irradiation (BMT/TBI) has adverse effects on growth, growth hormone status and adiposity. We investigated the GH-IGF-I axis in relation to adiposity.
  
  
  METHODS
  Cross-sectional case control study.
  
  
  METHODS
  BMT/TBI survivors (n = 22) and short stature control participants (n = 19), all GH-naïve or off GH treatment >3 months.
  
  
  METHODS
  Auxology, DEXA scans and GH-IGF-I axis investigation: (i) 12-h overnight GH profiles; (ii) insulin tolerance test (ITT); and (iii) IGF-I generation test.
  
  
  METHODS
  auto-deconvolution of GH profile data and comparison of quantitative parameters using ANOVA.
  
  
  RESULTS
  Eighty-two percent of BMT/TBI survivors had growth hormone deficiency (GHD) using ITT. GH profile area-under-the-curve (GH-AUC) was reduced in BMT/TBI survivors vs short stature control participants [geometric mean (range) 209 (21-825) vs 428 (64-1400) mcg/l/12 h, respectively, P = 0·007]. GHD was more marked in those who had additional cranial irradiation (CRT) [ITT peak 1·4 (0·2-3·0) vs TBI only 4·1 (1·1-14·8) mcg/l, P = 0·036]. GHD was more marked at the end of growth in BMT/TBI survivors vs short stature control participants (GH-AUC 551 (64-2474) vs 1369 (192-4197) mcg/l/12 h, respectively, P = 0·011) and more prevalent (9/11 vs 1/9, respectively, P = 0·005). GH profile data were consistent with ITT results in 80% of participants. IGF-I generation tests were normal. BMT/TBI survivors still demonstrated lower GH levels after adjustment for adiposity (fat-adjusted mean difference for GH-AUC 90·9 mcg/l/12 h, P = 0·025).
  
  
  CONCLUSIONS
  GHD was more prevalent in BMT/TBI survivors than expected for the CRT dose in TBI, worsened with time and persisted into adulthood. GHD could not be explained by adiposity. There was no evidence of GH neurosecretory dysfunction or resistance after BMT/TBI.
authors: Department of Paediatric Endocrinology and Diabetes, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors: N L
authors: NL
authors: Davis
authors: Department of Stem Cells, Ageing and Molecular Physiology Unit, Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Liverpool, UK.
authors: C E
authors: CE
authors: Stewart
authors: Department of Exercise and Sport Science, Manchester Metropolitan University, Crewe, Cheshire, UK.
authors: A D
authors: AD
authors: Moss
authors: Department of Paediatric Endocrinology and Diabetes, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors: W W W
authors: WW
authors: Woltersdorf
authors: School of Clinical Sciences, University of Bristol, Bristol, UK.
authors: L P
authors: LP
authors: Hunt
authors: Department of Paediatric Endocrinology and Diabetes, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors: R A
authors: RA
authors: Elson
authors: Department of Paediatric Oncology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors: J M
authors: JM
authors: Cornish
authors: School of Clinical Sciences, University of Bristol, Bristol, UK.
authors: M C G
authors: MC
authors: Stevens
authors: Department of Paediatric Endocrinology and Diabetes, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors: E C
authors: EC
authors: Crowne
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D008297:Male; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone