Growth Hormone, Insulin-like Growth Factor-1 Insulin-like Growth Factor Binding Protein-3

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1 6 1 2 : Growth Hormone, Insulin-like Growth Factor-1Insulin-like Growth Factor Binding Protein-3 Abstract Clinical Significance of Growth Hormone, Insulin-like Growth Factor-1, and Insulin-like Growth Factor Binding Protein-3 in Patients With Posthepatitic Liver Cirrhosis Jae Hyeon Moon, M.D., Do Hoon Kim, M.D., Jin Kwang An, M.D. Jun Hong Lee, M.D., Dae Hwan Kang, MD.,Geun Am Song, M.D. Mong Cho, M.D. and Ung Suk Yang, M.D. Department of Internal Medicine, College of Medicine, Pusan National University, Pusan, Korea Background/ Aims: Although an Insulin- like growth factor- 1(IGF- 1) and an Insulin- like growth factor binding protein- 3(IGFBP- 3) have been reported to be valuable indices of nutritional state in cirrhotic patients, there is still a dispute. T he controversy may be caused by the fact that most studies included heterogeneous groups of patients such as alcoholic and posthepatitic cirrhosis. T he aim of this study was two fold: to evaluate whether the Growth hormone(gh), IGF- 1, and the IGFBP- 3 are significant or not as valuable indices of hepatic function as well as the nutritional state in hepatitis B or C associated cirrhotic patients. Methods: T his study consisted of 36 patients with liver cirrhosis associated with hepatitis B or C. Patients with alcoholic cirrhosis were excluded. T he serum GH, IGF- 1, and IGFBP- 3 were measured while patients were fasting. T he variables of liver function and nutritional state included Child- Pugh score, serum bilirubin, albumin, prothrombin time, triceps skinfold thickness(t SF), and midarm muscle circumference (MAMC). T he correlation between the variables of liver function or nutritional state and the serum GH, IGF- 1, or IGFBP- 3 was evaluated. Res ults: T he IGF- 1 correlated very well with IGFBP- 3 (P<.1). Both the IGF- 1 and IGFBP- 3 correlated inversely with Child- Pugh score (P<.1, P<.1 respectively). IGFBP- 3 correlated very well with the serum bilirubin level as well as the albumin level (P<.1). Neither the IGF- 1 nor IGFBP- 3 showed any correlation with T SF or MAMC. Conclus ions: Both IGF- 1 and IGFBP- 3 were clinically significant as indices of hepatic function in the patients with hepatitic B or C associated cirrhosis but neither of them were significant as indices of nutritional state.(korean J Hepatol 2;6:52-58) Key Words : Grow th hormone, Insulin- like growth factor- 1, Insulin- like growth factor binding protein- 3, Liver cirrhosis 224; 231; 2314 Abbreviations: GH, grow th hormone; IGF- 1, insulin- like grow th factor- 1; IGFBP- 3, insulin- like grow th factor binding protein- 3; INR, international normalization ratio; MAC, midarm circumference; MAMC, midarm muscle circumference; T SF, triceps skinfold thickness :, 11,, () Phone: 51) ,7516; FAX: 51) ; E- mail: mc1128@hyow on.pusan.ac.kr

2 Jae Hyeon Moon, et al. Clinical Significance of Growth Hormone, Insulin- like Growth Factor- 1, and Insulin- like Growth Fa ctor Binding Protein- 3 in Patients With Posthepa titic Liver Cirrhosis 53 Insulin- like growth growth factor- 1 (IGF- 1)Insulin- like factor binding protein- 3 (IGFBP- 3) (anthropometry),1 growth hormone (GH). IGFBP- 3,, triceps skinfold thickeness IGF- 1IGF- 1 (T SF)midarm circumference (MAC), IGF- 1 midarm muscle circumference (MAMC), IGF- 1. IGFBP IGF IGF- 1 GH (feedback mechanism) (RIA)Child- Pugh GHGH score, (prothrombin time),.6,, T SF, MAMC,. 7,8., 9. GH, IGF- 1, IGFBP- 3.. GH, IGF- 1, IGFBP- 3.. Child- Pugh A, B, C 12. MAMC (cm) = MAC (cm)-.314tsf (mm) GH, IGF- 1, IGFBP- 3 SPSS/PC+ Spearman, Child- Pugh Kruskal- Wallis MAMC,.,,.269, -.299, -.16, (), (),. (.361, p<.1) (2).,,,,,.1.584,.385 (, p<.1, p<.5), Child- Pugh,,, 2 2. Serum GH GH Child- Pugh score, T SF 3. Serum IGF-1 IGF- 1 IGFBP- 3, score(-.448), (INR)(-.415)

3 ( p<.1, p<.5)., (T SF.47, MAMC -.422,.548,.412; p<.5)( 1)..11) (, ( r,t S F -.75, M A M C 2). Child- Pugh A B, B C 2). IGF- 1 Child- Pugh A A C B, B C (p<.5)(3). 4. Serum IGFBP-3 IGFBP- 3 Child- Pugh score (r,-.67; p<.1), (INR),,, (r,-.588,.79) ( A C (p<.5)(3). Child- Pugh A CGH T able 1. Clinical and Biochemical Profiles of Cirrhotic Patients Child- Pugh A Child- Pugh B Child- Pugh C Patients Numbers Male/ Female Age(years)* Child- Pugh scores* Prothrombin time(inr) Bilirubin(mg/dl) Albumin(g/dl) Ascites Encephalopathy grade3 12 8/4 51(4-61) 5.58(5-6) /4 58(4-74) 8.33(7-9) /9 51(37-62) 11.5(1-14) *median(range), meansd T able 2. Correlation Coefficients between GH, IGF- 1, IGFBP- 3 and Liver Function Profiles, Anthropometric Parameters GH IGF- 1 IGFBP- 3 Child- Pugh scores Prothrombin time(inr) Bilirubin Albumin T SF MAMC Lymphocyte counts GH IGF- 1 IGFBP * -.488* * -.67* -.588* * *p<.5, p<.1

4 7. Growth Hormone, Insulin- like Growth Factor- 1Insulin- like Growth Factor Binding Protein T able 3. Comparison of GH, IGF- 1, IGFBP- 3 among Child- Pugh Groups Child- Pug h A m edian(range) Child- Pugh B m edian(range) Child- Pug h C m edian(rang e) P v alue (A v s B) P value (B vs C) P value (A vs C) GH(ng/ m l) IGF - 1(ng/ m l) IGF BP- 3(ng/ m l) 1.3(.2-.7) 4.3( ) ( ) 4.2( ) 2.7( ) ( ) 5.1(.1-29.) 15.( ) 735.9( ) <.5 <.5 : not significant IGF- 1. GH IGF IGF- 1 (INR)Child- IGF- 1 Pugh AC GH GH. GH,13 (anorexia nervosa)14. (critical illness),15 IGFBP- 35 IGF- 198% IGF IGF, IGF- 1. GH.2,21 Zapf 22Donaghy 5 IGFBP- 3, Child- Pugh score.16 IGFBP- 3 IGF- 1. IGFBP Child- Pugh.18 (,, ).. 19 IGF- 1 IGF- 1. IGF- 1. IGF- 1 2,3 IGF- 1 (lean body mass). IGF- 1 IGFBP- 3 IGF- 1.

5 56 The Korean Journal of Hepatology : Vol. 6. No Figure 1. Scatter plot of serum IGFBP- 3 and the variables of liver function profiles and Child-Pugh scores. r:correlation coefficient. : IGF- 1IGFBP- 3 (anthropometry)gh, IGF- 1, IGFBP- 3, (prothrombin. time),,, : GH, IGF- 1, IGFBP- 3 IGF- 1. IGFBP- 3 GH, IGF- 1, IGFBP- 3 (p<.1),. : 36Child- Pugh,. IGF- 1 IGFBP- 3 Child- Pugh, score ( p<.1,

6 Jae Hyeon Moon, et al. Clinical Significance of Growth Hormone, Insulin- like Growth Factor- 1, and Insulin- like Growth Fa ctor Binding Protein- 3 in Patients With Posthepa titic Liver Cirrhosis 57 p<.1). IGF- 1IGFBP- 3 T SFMAMC tology. 1995;21: , 6. Isley WL, Underwood LE, Clemmons DR. (INR) Changes in plasma somatomedin- C in ( p<.5), IGFBP- 3 response to ingestion of diets w ith variable (p<.1). protein and energy content. J Parenter : IGF- 1IGFBP- 3 Child- Pugh score enteral Nutr, 1984;8: Untermann TG, Vazquez RM, Slas AJ, Martyn PA, Phillips LS. Nutrition and somatomedin. XIII. Usefulness of somatomedin- C in nutritional. IGF- 1 assessment. Am J Med 1985;78: , IGFBP Burgess EJ. Insulin- like growth factor 1: a valid nutritional indicator during parenteral, feeding of patients suffering an acute phase response. Ann Clin Biochem 1992;29: Caregaro L, Alberino F, Amodio P, et al. Nutritional and prognostic significance of :,,, - 3 insulin- like growth factor- 1 in patients w ith liver cirrhosis. Nutrition 1997;13: Sherlock S, Dooley J. Disease of the liver and biliary system. London: Blackwell 1. Baxter RC. The somatomedins: Insulin- like Scientific, 1997; Frisancho AR. New norm of upper limb fat growth factors. Adv Clin Chem 1986;25: Eriksson S. Insulin- like growth factor- 1 in and muscle areas for assessment of nutritional status. Am J Clin Nutr 1981;34: chronic liver disease. J Intern Med 12. Hattori N, Kurahachi H, Ikekubo K, et al. 1994;235: Serum growth hormone- binding proten, 3. Buzzelli G, Dattolo P, Pinzani M, Brocchi A, insulin- like growth factor- 1, and growth Romano S, Gentilini P. Circulating growth hormone in patients with liver cirrhosis. hormone and insulin- like growth factor- I in Metabolism 1992;41: nonalcoholic liver cirrhosis with or without 13. Cotterill AM, Holly JMP, Wass JAH. T he superimposed hepatocarcinoma: evidence of regulation of insulin- like growth factor an altered circadian rhythm. Am J Gastroenterol binding protein(igfbp)- 1 during prolonged 1993;88: fasting. Clin Endocrinol 1993;39: Shaarawy M, Fikry MA, Massoud BA, 14. Counts DR, Gw irtsman H, Carlsson LM, Lofty S. Insulin- like growth factor binding Lesem M, Cutler GJ. T he effect of protein- 3: A novel biomarker for the anorexia nervosa and refeeding on growth assessment of the synthetic capacity of hormone- binding protein, the insulin- like growth hepatocytes in liver cirrhosis. J Clin factors(igfa), and the IGF- binding proteins. J Endocrinol Metab 1998;83: Donaghy A, Rose R, Gimson A, Hughes SC, Clin Endocrinol Metab 1992;75: Ross R, Miell J, Freeman E, et al. Critically Holly J, Williams R. GH, IGF- 1 and ill patients have high basal growth hormone IGFBP- 3 in chronic liver disease. Hepa- levels with attenuated oscillatory activity

7 associated with low levels of insulin- like growth factor- 1. Clin Endocrinol 1991;35: T avil AS. T he synthesis and degradation of liver produced proteins. Gut 1972;13: T aylor AL, Lipman RL, Salam A, Mintz DH. Hepatic clearance of human growth hormone. J Clin Endoclinol 1972;34: Mendenhall CL, Chernhausek SD, Ray MB, et al. T he interactions of insulin- like growth factor- 1(IGF- 1) with protein- calorie malnutrition in patients with alcoholic liver disease: VA Cooperative study on Alcoholic Hepatitis V1. Alcohol 1989;24: Holly JMP, Wass JAH. Insulin- like growth factors; autocrine, paracrine or endocrine? New perspectives of the somatomedin hypothesis in the light of recent developments. J Endocrinol 1989;122: Bar RS, Harrison LC, Baxter RC, et al. Production of IGF- binding proteins by vascular endothlial cells. Biochem Biophys Res Commun 1987;148: Conover CA. Potentiation of insulin- like growth factor(igf) action by IGF- binding protein- 3: Studies of underlying mechanism. Endocrinology 1992;13: Zapf J, Kiefer M, Merrweather JU, et al. Isolation from adult human serum of four IGFBPs and molecular cloning of one of them. J Biol Chem. 199;265: