Horm Metab Res 2018; 50(03): 250-256
DOI: 10.1055/s-0043-124970
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Reduced Growth Hormone Secretion is Associated with Nonalcoholic Fatty Liver Disease in Obese Children

Shuang Liang
1   Department of Pediatrics, The Second Hospital of Shandong University, Shandong, China
,
Zhen Yu
2   Department of Pediatrics, Shandong University Qilu Hospital, Shandong, China
,
Xiaobo Song
3   Department of Pediatrics, Children’s Hospital of Changchun, Jilin, China
,
Yu Wang
4   Department of Gastroenterology, The Sixth People Hospital of Jinan City, Shandong, China
,
Meng Li
5   Department of Radiology, The Sixth People Hospital of Jinan City, Shandong, China
,
Jiang Xue
1   Department of Pediatrics, The Second Hospital of Shandong University, Shandong, China
› Author Affiliations
Further Information

Publication History

received 24 July 2017

accepted 06 December 2017

Publication Date:
16 January 2018 (online)

Abstract

The purpose of the study was to evaluate the relationship between arginine-levodopa-induced growth hormone (GH) secretion and nonalcoholic fatty liver disease (NAFLD) in obese children. This study includes a total of 84 obese and 43 normal weight children. The obese subjects are divided into two groups based on the presence or absence of NAFLD. Clinical examination, anthropometric and laboratory examinations, and liver ultrasonography are assessed for all participants. The obese group had significantly lower peak stimulated GH (p<0.001) and lower insulin-like growth factor 1 (IGF-1) (p<0.001) compared with the control group. Children with NAFLD had significantly lower peak stimulated GH (p<0.001) and lower IGF-1 (p=0.022) compared with non-NAFLD group. Results from logistic regression model showed that only peak GH after stimulation test was inversely associated with NAFLD (p=0.015), while body mass index (BMI) was positively associated with NAFLD (p=0.03). Among 84 obese children and adolescents, peak stimulated GH was negatively associated with alanine aminotransferase (r=–0.394, p<0.001), BMI (r=–0.571, p<0.001), systolic blood pressure (r=–0.223, p=0.041), diastolic blood pressure (r=–0.272, p=0.012), homeostasis model assessment of insulin resistance (r=–0.369, p=0.001), insulin (r=–0.382, p<0.001), and positively associated with high density lipoprotein cholesterol (r=0.275, p=0.011). Our study confirms a significant inverse relationship between NAFLD and GH response to standard stimulation testing in obese children without known hypothalamic/pituitary disease.

 
  • References

  • 1 Argente J. Multiple Endocrine abnormalities of the growth hormone and insulin-like growth factor axis in prepubertal children with exogenous obesity: Effect of short- and long-term weight reduction. J Clin Endocrinol Metab 1997; 82: 2076-2083
  • 2 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
  • 3 Cordido F, Garcia-Buela J, Sangiao-Alvarellos S, Martinez T, Vidal O. The decreased growth hormone response to growth hormone releasing hormone in obesity is associated to cardiometabolic risk factors. Mediators Inflamm 2010; 434562:
  • 4 Makimura H, Stanley T, Mun D, Chen C, Wei J, Connelly JM, Hemphill LC, Grinspoon SK. Reduced growth hormone secretion is associated with increased carotid intima-media thickness in obesity. J Clin Endocrinol Metab 2009; 94: 5131-5138
  • 5 Rizzo M, Mikhailidis DP. Lipoprotein alterations and reduced growth hormone secretion: Relationships with obesity and cardiovascular risk 1. Clin Endocrinol (Oxf) 2012; 76: 177-178
  • 6 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
  • 7 Utz AL, Yamamoto A, Hemphill L, Miller KK. Growth hormone deficiency by growth hormone releasing hormone-arginine testing criteria predicts increased cardiovascular risk markers in normal young overweight and obese women. J Clin Endocrinol Metab 2008; 93: 2507-2514
  • 8 Manco M, Bottazzo G, DeVito R, Marcellini M, Mingrone G, Nobili V. Nonalcoholic fatty liver disease in children. J Am Coll Nutr 2008; 27: 667-676
  • 9 Gardner CJ, Irwin AJ, Daousi C, McFarlane IA, Joseph F, Bell JD, Thomas EL, Adams VL, Kemp GJ, Cuthbertson DJ. Hepatic steatosis, GH deficiency and the effects of GH replacement: A Liverpool magnetic resonance spectroscopy study. Eur J Endocrinol 2012; 166: 993-1002
  • 10 Nishizawa H, Iguchi G, Murawaki A, Fukuoka H, Hayashi Y, Kaji H, Yamamoto M, Suda K, Takahashi M, Seo Y, Yano Y, Kitazawa R, Kitazawa S, Koga M, Okimura Y, Chihara K, Takahashi Y. Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy. Eur J Endocrinol 2012; 167: 67-74
  • 11 Fusco A, Miele L, D'Uonnolo A, Forgione A, Riccardi L, Cefalo C, Barini A, Bianchi A, Giampietro A, Cimino V, Landolfi R, Grieco A, De Marinis L. Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels. Clin Endocrinol (Oxf) 2012; 77: 531-536
  • 12 Bredella MA, Torriani M, Thomas BJ, Ghomi RH, Brick DJ, Gerweck AV, Miller KK. Peak growth hormone-releasing hormone-arginine-stimulated growth hormone is inversely associated with intramyocellular and intrahepatic lipid content in premenopausal women with obesity. J Clin Endocrinol Metab 2009; 94: 3995-4002
  • 13 Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y, Taura N, Shibata H, Fujimoto M, Toriyama K, Eguchi K. Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatol Int 2007; 1: 287-294
  • 14 Li H, Ji CY, Zong XN, Zhang YQ. Body mass index growth curves for Chinese children and adolescents aged 0 to 18 years. Chin J Pediatrics 2009; 47: 493-498
  • 15 The Chinese National Workshop on Fatty Liver and Alcohol&Liver Diseasefor the Chinese Liver Disease Assocication . Guidelines for management of nonalcoholic fatty liverdisease. Chin J Hepatol 2010; 49: 18-20
  • 16 Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976; 51: 170-179
  • 17 Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  • 18 Vanderschueren-Lodeweyckx M. The effect of simple obesity on growth and growth hormone. Horm Res Paediat 1993; 40: 23-30
  • 19 Ballerini MG, Ropelato MG, Domené HM, Pennisi P, Heinrich JJ, Jasper HG. Differential impact of simple childhood obesity on the components of the growth hormone-insulin-like growth factor (IGF)-IGF binding proteins axis. Journal of Pediatric Endocrinology and Metabolism J Pediatr Endocr Met 2004; 17: 749-758
  • 20 Gleeson HK, Lissett CA, Shalet SM. Insulin-like growth factor-I response to a single bolus of growth hormone is increased in obesity. J Clin Endocrinol Metab 2005; 90: 1061-1067
  • 21 Attia N, Tamborlane WV, Heptulla R, Maggs D, Grozman A, Sherwin RS, Caprio S. The metabolic syndrome and insulin-like growth factor i regulation in adolescent obesity 1. J Clin Endocrinol Metab 1998; 83: 1467-1471
  • 22 Shalitin S, Phillip M. Role of obesity and leptin in the pubertal process and pubertal growth–a review. Int J Obes Relat Metab Disord 2003; 27: 869-874
  • 23 Geffner ME. The growth without growth hormone syndrome. Endocrinol Metab Clin North Am 1996; 25: 649-663
  • 24 Liang S, Cheng X, Hu Y, Song R, Li G. Insulin-like growth factor 1 and metabolic parameters are associated with nonalcoholic fatty liver disease in obese children and adolescents. Acta Paediat 2017; 106: 298-303
  • 25 Utzschneider KM, Kahn SE. Review: The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2006; 91: 4753-4761
  • 26 Melmed S. Insulin suppresses growth hormone secretion by rat pituitary cells. J Clin Invest 1984; 73: 1425
  • 27 Stanković MN, Mladenović DR, Đuričić I, Šobajić SS, Timić J, Jorgačević B, Aleksić V, Vučević DB, Ješić-Vukićević R, Radosavljević TS. Time-dependent changes and association between liver free fatty acids, serum lipid profile and histological features in mice model of nonalcoholic fatty liver disease. Arch Med Res 2014; 45: 116-124
  • 28 Casanueva F, Villanueva L, Dieguez C, Diaz Y, Cabranes J, Szoke B, Scanlon M, Schally AV, Fernandez-Cruz A. Free Fatty Acids Block Growth Hormone (GH) Releasing Hormone-Stimulated GH Secretion in Man Directly at the Pituitary. J Clin Endocrinol Metab 1987; 65: 634-642
  • 29 Tarantino G. Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance. World J Gastroenterol 2010; 16: 4773
  • 30 Kirsz K, Szczesna M, Dudek K, Bartlewski PM, Zieba DA. Influence of season and nutritional status on the direct effects of leptin, orexin-A and ghrelin on luteinizing hormone and growth hormone secretion in the ovine pituitary explant model. Domest Anim Endocrinol 2014; 48: 69-76
  • 31 Eden Engstrom B, Burman P, Holdstock C, Karlsson FA. Effects of growth hormone (GH) on ghrelin, leptin, and adiponectin in GH-deficient patients. J Clin Endocrinol Metab 2003; 88: 5193-5198
  • 32 Savastano S, Di Somma C, Pizza G, De Rosa A, Nedi V, Rossi A, Orio F, Lombardi G, Colao A, Tarantino G. Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females. J Transl Med 2011; 9: 136