Horm Metab Res 2013; 45(10): 748-753
DOI: 10.1055/s-0033-1347243
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Body Fat Mass is a Strong and Negative Predictor of Peak Stimulated Growth Hormone and Bone Mineral Density in Healthy Adolescents During Transition Period

M. Perotti
1   Clinica Medica, Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
,
S. Perra
1   Clinica Medica, Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
,
A. Saluzzi
1   Clinica Medica, Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
,
G. Grassi
1   Clinica Medica, Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
2   IRCCS Multimedica, Sesto San Giovanni, Milan, Italy
,
A. I. Pincelli
1   Clinica Medica, Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
› Author Affiliations
Further Information

Publication History

received 03 March 2013

accepted 07 May 2013

Publication Date:
02 August 2013 (online)

Abstract

The adipose tissue has detrimental effects on growth hormone secretion, even in the absence of obesity. The majority of previous studies have shown an inverse relationship between fat mass and the growth hormone response to several stimulation tests in adults and in children. The contribution of body fat mass on growth hormone response to provocative tests during the transition age is not known. We analyzed the GH-IGF1 axis by GHRH-arginine test in 30 healthy adolescents with normal stature during the transition period from 14 to 18 years. All subjects underwent body composition analysis by dual-energy X-ray absorptiometry (DXA). We found that total body fat mass was inversely correlated with peak GH to provocative test (r=−0.6, p=0.004). GH deficiency was shown in 2 of our healthy patients if diagnosis was based on GH peak below 19 μg/l. Both children who failed the GHRH-arginine were overweight (BMI for age above 85th percentile). However, their GH status was normal when assessed by insulin tolerance test. Multivariate analysis demonstrated strong correlation between peak stimulated GH and measures of body adiposity, including body mass index and fat mass index, with the latter showing the most important effect on GH secretion. Fat mass index alone explained 34.5% of the variability in peak GH. This study has shown for the first time that during the transition period, GH response to GHRH-arginine test is strongly influenced by body composition, and cutoff values appropriate for overweight and obese adolescents are needed.

Supporting Information

 
  • References

  • 1 Corneli G, Di Somma C, Prodam F, Bellone J, Bellone S, Gasco V, Baldelli R, Rovere S, Schneider HJ, Gargantini L, Gastaldi R, Ghizzoni L, Valle D, Salerno M, Colao A, Bona G, Ghigo E, Maghnie M, Aimaretti G. Cut-off limits of the GH response to GHRH plus arginine test and IGF-I levels for the diagnosis of GH deficiency in late adolescents and young adults. Eur J Endocrinol 2007; 157: 701-708
  • 2 Maghnie M, Aimaretti G, Bellone S, Bona G, Bellone J, Baldelli R, de Sanctis C, Gargantini L, Gastaldi R, Ghizzoni L, Secco A, Tinelli C, Ghigo E. Diagnosis of GH deficiency in the transitino period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement. Eur J Endocrinol 2005; 152: 589-596
  • 3 Biller BM, Samuels MH, Zagar A, Cook DM, Arafah BM, Bonert V, Stavrou S, Kleinberg DL, Chipman JJ, Hartman ML. Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2002 87. 2067-2079
  • 4 Maccario M, Gauna C, Procopio M, Di Vito L, Rossetto R, Oleandri SE, Grottoli S, Ganzaroli C, Aimaretti G, Ghigo E. Assessment of GH/IGF-I axis in obesity by evaluation of IGF-I levels and the GH response to GHRH+arginine test. J Endocrinol Invest 1999; 22: 424-429
  • 5 Maccario M, Valetto MR, Savio P, Aimaretti G, Baffoni C, Procopio M, Grottoli S, Oleandri SE, Arvat E, Ghigo E. Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency. Int J Obes Relat Metab Disord 1997; 21: 27-32
  • 6 Scacchi M, Pincelli AI, Cavagnini F. Growth hormone in obesity. Int J Obes Relat Metab Disord 1999; 23: 260-271
  • 7 Corneli G, Di Somma C, Baldelli R, Rovere S, Gasco V, Croce CG, Grottoli S, Maccario M, Colao A, Lombardi G, Ghigo E, Camanni F, Aimaretti G. The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Eur J Endocrinol 2005; 153: 257-264
  • 8 Bonert VS, Elashoff JD, Barnett P, Melmed S. Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: diagnostic caveat for adult GH deficiency. J Clin Endocrinol Metab 2004; 89: 3397-3401
  • 9 Makimura H, Stanley T, Mun D, You SM, Grinspoo S. The effects of central adiposity on growth hormone (GH) response to GH-releasing hormonearginine stimulation testing in men. J Clin Endocrinol Metab 93: 4254-4260
  • 10 Stanley TL, Levitsky LL, Grinspoon SK, Misra M. Effect of body mass index on peak growth hormone response to provocative testing in children with short stature. J Clin Endocrinol Metab 2009; 94: 4875-4881
  • 11 Loche S, Guzzetti C, Pilia S, Ibba A, Civolani P, Porcu M, Minerba L, Casini MR. Effect of body mass index on the growth hormone response to clonidine stimulation testing in children with short stature. Clin Endocrinol 2011; 74: 726-731
  • 12 Loche S, Cappa M, Borrelli P, Faedda A, Crinò A, Cella SG, Corda R, Müller EE, Pintor C. Reduced growth hormone response to growth hormone-releasing hormone in children with simple obesity: evidence for somatomedin-C mediated inhibition. Clin Endocrinol 1987; 27: 145-153
  • 13 Perotti M, Caumo A, Brunani A, Cambiaghi N, Casati M, Scacchi M, Perra S, Rocco C, Mancia G, Grassi G, Cavagnini F, Pincelli AI. Postprandial triglyceride profile after a standardized oral fat load is altered in growth hormone (GH)-deficient adult patients and is not improved after short-term GH replacement therapy. Clin Endocrinol 2012; 77: 721-727
  • 14 Pritchard JE, Nowson CA, Strauss BJ, Carlson JS, Kaymakci B, Wark JD. Evaluation of dual energy X-ray absorptiometry as a method of measurement of body fat. Eur J Clin Nutr 1993; 47: 216-228
  • 15 Schutz Y, Kyle UU, Pichard C. Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98 y. Int J Obes Relat Metab Disord 2002; 26: 953-960
  • 16 Growth Hormone Research Society . Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab 2000; 85: 3990-3993
  • 17 American Cook DM, Yuen KC, Biller BM, Kemp SF, Vance ML. American Association of Clinical Endocrinologists. Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients – 2009 update. Endocr Pract 2009; 15: 1-29
  • 18 Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE, Hilsted J, Skakkebae NE. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab 1995; 80: 1407-1415
  • 19 Bengtsson BA, Eden S, Lonn L, Kvist H, Stokland A, Lindstedt G, Bosaeus I, Tolli J, Sjostrom L, Isaksson OG. Treatment of adults with growth hormone deficiency with recombinant human GH. J Clin Endocrinol Metab 1993; 76: 309-317
  • 20 Binnerts A, Swart GR, Wilson JH, Hoogerbrugge N, Pols HA, Birkenhager JC, Lamberts SW. The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol 1992; 37: 79-87
  • 21 Shadid S, Jensen MD. Effects of growth hormone administration in human obesity. Obes Res 2003; 11: 170-175
  • 22 Albert SG, Mooradian AD. Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity. J Clin Endocrinol Metab 2004; 89: 695-701
  • 23 Rasmussen MH. Obesity, growth hormone and weight loss. Mol Cell Endocrinol 2010; 316: 147-153
  • 24 Roemmich JN, Clark PA, Weltman A, Veldhuis JD, Rogol AD. Pubertal alterations in growth and body composition: IX. Altered spontaneous secretion and metabolic clearance of growth hormone in overweight youth. Metabolism 2005; 54: 1374-1383
  • 25 Müller EE, Locatelli V, Cocchi D. Neuroendocrine control of growth hormone secretion. Physiol Rev 1999; 79: 511-607
  • 26 Misra M, Bredella MA, Tsai P, Mendes N, Miller KK, Klibanski A. Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol Endocrinol Metab 2008; 295: E385-E392
  • 27 Jessup SK, Dimaraki EV, Symons KV, Barkan AL. Sexual dimorphism of growth hormone (GH) regulation in humans: endogenous GH-releasing hormone maintains basal GH in women but not in men. J Clin Endocrinol Metab 2003; 88: 4776-4780
  • 28 Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML. Endocrine Society’s Clinical Guidelines Subcommittee, Stephens PA. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2006; 91: 1621-1634
  • 29 Juul A. Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Horm IGF Res 2003; 13: 113-170
  • 30 Perrini S, Laviola L, Carreira MC, Cignarelli A, Natalicchio A, Giorgino F. The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J Endocrinol 2010; 205: 201-210
  • 31 Vijayakumar A, Yakar S, Leroith D. The intricate role of growth hormone in metabolism. Front Endocrinol 2011; 2: 32
  • 32 Perrini S, Laviola L, Carreira MC, Cignarelli A, Natalicchio A, Giorgino F. The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J Endocrinol 2010; 205: 201-210
  • 33 Glynn N, Agha A. Diagnosing growth hormone deficiency in adults. Int J Endocrinol. 2012 2012. 972-617
  • 34 Wells JC, Coward WA, Cole TJ, Davies PS. The contribution of fat and fat-free tissue to body mass index in contemporary children and the reference child. Int J Obes Relat Metab Disord 2002; 26: 1323-1328
  • 35 Conway GS, Szarras-Czapnik M, Racz K, Keller A, Chanson P, Tauber M, Zacharin M. 1369 GHD to GHDA Transition Study Group. Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency. Eur J Endocrinol 2009; 160: 899-907
  • 36 Dimitri P, Bishop N, Walsh JS, Eastell R. Obesity is a risk factor for fracture in children but is protective against fracture in adults: a paradox. Bone 2012; 50: 457-466
  • 37 Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: an update. Clin Endocrinol 2006; 64: 355-365
  • 38 Van Loan MD, Johnson HL, Barbieri TF. Effect of weight loss on bone mineral content and bone mineral density in obese women. Am J Clin Nutr 1998; 67: 734-738