Effect of Short-Term Administration of Growth Hormone on Serum IGF-1 and Nutritional Status in Patients after Gastrointestinal Surgery_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Mingming , ZHOU Yong , WU Xiaoting

*Surgery Center of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Growth hormone; Insulin-like growth factor; Nutrition support; Gastrointestinal surgery

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Objective To investigate the effect of short-term administration of growth hormone (GH) on serum insulin-like growth factor-1 (IGF-1) level and nutritional status in patients after gastrointestinal operation, and evaluate whether postoperative application of GH rise the risk of tumor recurrence. Methods Forty-eight patients undergoing major gastrointestinal operation were randomly divided into two groups: GH group （n=24） and control group （n=24）. The two groups received isocaloric isonitrogenous nutrition with daily injection of either GH 0.15 U/kg or placebo for a period of day 3-9 postoperatively. Serum albumin, fibronectin, and IGF-1 were measured before operation as a baseline, and day 3 and 10 after operation using standard laboratory techniques. Nitrogen balance was measured daily from day 3 to day 9 after operation. Postoperative complications and adverse reaction were observed. All cancer patients received regular abdominal B-type ultrasonography and chest X-ray examination during 2 years of follow-up. Results Compared with control group, GH treatment did not influence serum IGF-1 and serum albumin level （P gt;0.05）, but improved significantly the rise from day 3 to day 10 of serum fibronectin level 〔(22.8±5.8) mg/L vs.（9.6±3.6） mg/L， P＜0.05〕 and the cumulative nitrogen balance 〔（11.37±16.82） g vs.（－9.11±17.52） g， P＜0.01〕 postoperatively. There was no severe adverse effects and complications during GH treatment. The tumor-recurrence rates were not statistically different between two groups during follow-up. Conclusions Short-term administration of low-dose GH combined with early nutrition support can improve total nitrogen retention and protein metabolism, but not influence serum IGF-1 level after major abdominal surgery. Short-term administration of low-dose GH may not cause the tumor-recurrence.

Citation： ZHANG Mingming,ZHOU Yong,WU Xiaoting. Effect of Short-Term Administration of Growth Hormone on Serum IGF-1 and Nutritional Status in Patients after Gastrointestinal Surgery. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(12): 968-973. doi: Copy

1.	Kreymann KG. Early nutrition support in critical care: a European perspective [Ｊ]. Curr Opin Clin Nutr Metab Care, 2008; 11(2): 156-159.
2.	Scurlock C, Mechanick JI. Early nutrition support in the intensive care unit: a US perspective [Ｊ]. Curr Opin Clin Nutr Metab Care, 2008; 11(2): 152-155.
3.	罗世成, 郭建辉, 朱军, 等. 胃肠道肿瘤患者术后早期肠内营养与肠外营养支持的随机对照研究 [Ｊ]. 中国普外基础与临床杂志, 2007; 14(3): 324-328.
4.	Kudsk KA. Immunonutrition in surgery and critical care [Ｊ]. Annu Rev Nutr, 2006; 26: 463-479.
5.	张明鸣, 伍晓汀. 肠康复治疗和短肠综合征 [Ｊ]. 中国普外基础与临床杂志, 2007; 14(1): 117-119.
6.	陈先锋, 刘作金, 李旭宏, 等. TPN联合生长激素对胃肠道恶性肿瘤患者术后应激反应的抑制作用 [Ｊ]. 中国普外基础与临床杂志, 2006; 13(1): 45-47.
7.	Akaza H, Matsuki K, Matsushima H, et al. Stimulatory effects of growth hormone on rat bladder carcinogenesis [Ｊ]. Cancer, 1991; 68(11): 2418-2421.
8.	Maneatis T, Baptista J, Connelly K, et al. Growth hormone safety update from the National Cooperative Growth Study [Ｊ]. J Pediatr Endocrinol Metab, 2000; 13 Suppl 2: 1035-1044.
9.	Tacke J, Bolder U, Herrmann A, et al. Long-term risk of gastrointestinal tumor recurrence after postoperative treatment with recombinant human growth hormone [Ｊ]. JPEN J Parenter Enteral Nutr, 2000; 24(3): 140-144.
10.	Lang CH, Frost RA. Role of growth hormone, insulin-like growth factor-Ⅰ, and insulin-like growth factor binding proteins in the catabolic response to injury and infection [Ｊ]. Curr Opin Clin Nutr Metab Care, 2002; 5(3): 271-279.
11.	Mller N, Jrgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects [Ｊ]. Endocr Rev, 2009; 30(2): 152-177.
12.	Luo SM, Liang LJ, Lai JM. Effects of recombinant human growth hormone on remnant liver after hepatectomy in hepatocellular carcinoma with cirrhosis [Ｊ]. World J Gastroenterol, 2004; 10(9): 1292-1296.
13.	Duska F, Fric M, Waldauf P, et al. Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma: effects on nitrogen balance, insulin resistance, and substrate oxidation [Ｊ]. Crit Care Med, 2008; 36(6): 1707-1713.
14.	Hammarqvist F, Sandgren A, Andersson K, et al. Growth hormone together with glutamine-containing total parenteral nutrition maintains muscle glutamine levels and results in a less negative nitrogen balance after surgical trauma [Ｊ]. Surgery, 2001; 129(5): 576-586.
15.	Jensen MB, Kissmeyer-Nielsen P, Laurberg S. Perioperative growth hormone treatment increases nitrogen and fluid balance and results in short-term and long-term conservation of lean tissue mass [Ｊ]. Am J Clin Nutr, 1998; 68(4): 840-846.
16.	Jones CH, Newstead CG, Will EJ, et al. Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure [Ｊ]. Nephrol Dial Transplant, 1997; 12(7): 1406-1413.
17.	Akenami FO, Koskiniemi M, Siimes MA, et al. Assessment of plasma fibronectin in malnourished Nigerian children [Ｊ]. J Pediatr Gastroenterol Nutr, 1997; 24(2): 183-188.
18.	Heemskerk VH, Daemen MA, Buurman WA. Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in immunity and inflammation [Ｊ]. Cytokine Growth Factor Rev, 1999; 10(1): 5-14.
19.	Berneis K, Keller U. Metabolic actions of growth hormone: direct and indirect [Ｊ]. Baillieres Clin Endocrinol Metab, 1996; 10(3): 337-352.
20.	LeRoith D, Yakar S. Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1 [Ｊ]. Nat Clin Pract Endocrinol Metab, 2007; 3(3): 302-310.
21.	Hayes VY, Urban RJ, Jiang J, et al. Recombinant human growth hormone and recombinant human insulin-like growth factor Ⅰ diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects [Ｊ]. J Clin Endocrinol Metab, 2001; 86(5): 2211-2219.
22.	Mauras N, Haymond MW. Are the metabolic effects of GH and IGF-Ⅰ separable ? [Ｊ]. Growth Horm IGF Res, 2005; 15(1): 19-27.
23.	Mauras N, Martinez V, Rini A, et al. Recombinant human insulin-like growth factor Ⅰ has significant anabolic effects in adults with growth hormone receptor deficiency: studies on protein, glucose, and lipid metabolism [Ｊ]. J Clin Endocrinol Metab, 2000; 85(9): 3036-3042.
24.	Shimoda N, Tashiro T, Yamamori H, et al. Effects of gr-owth hormone and insulin-like growth factor-1 on protein metabolism, gut morphology, and cell-mediated immunity in burned rats [Ｊ]. Nutrition, 1997; 13(6): 540-516.
25.	Nakhjavani M, Esteghamati A, Hamidi S, et al. Changes in growth hormone and insulin-like growth factor-Ⅰ levels in the acute stage after open heart surgery and at the time of discharge [Ｊ]. Exp Clin Endocrinol Diabetes, 2009; 117(8): 413-416.
26.	Cao J, Luo SM, Liang L, et al. Effects of parenteral nutrition without and with growth hormone on growth hormone/insulin-like growth factor-1 axis after hepatectomy in hepatocellular carcinoma with liver cirrhosis [Ｊ]. JPEN J Parenter Enteral Nutr, 2007; 31(6): 496-501.
27.	Inaba T, Saito H, Fukushima R, et al. Insulin-like growth factor 1 has beneficial effects, whereas growth hormone has limited effects on postoperative protein metabolism, gut integrity, and splenic weight in rats with chronic mild liver injury [Ｊ]. JPEN J Parenter Enteral Nutr, 1997; 21(2): 55-62.
28.	Sevette A, Smith RC, Aslani A, et al. Does growth hormone allow more efficient nitrogen sparing in postoperative patients requiring parenteral nutrition? A double-blind, placebo-controlled randomised trial [Ｊ]. Clin Nutr, 2005; 24(6): 943-955.
29.	Sánchez-Gómez M, Malmlf K, Mejía W, et al. Insulin-like growth factor-Ⅰ, but not growth hormone, is dependent on a high protein intake to increase nitrogen balance in the rat [Ｊ]. Br J Nutr, 1999; 81(2): 145-152.
30.	Tacke J, Bolder U, Lhlein D. Improved cumulated nitrogen balance after administration of recombinant human growth hormone in patients undergoing gastrointestinal surgery [Ｊ]. Infusionsther Transfusionsmed, 1994; 21(1): 24-29.
31.	Ng EH, Rock CS, Lazarus D, et al. Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model [Ｊ]. J Surg Res, 1991; 51(2): 99-105.
32.	Wolf RF, Ng B, Weksler B, Burt M, et al. Effect of growth hormone on tumor and host in an animal model [Ｊ]. Ann Surg Oncol, 1994; 1(4): 314-320.
33.	Torosian MH. Growth hormone and prostate cancer growth and metastasis in tumor-bearing animals [Ｊ]. J Pediatr Endocrinol, 1993; 6(1): 93-97.
34.	Bartlett DL, Charland S, Torosian MH. Growth hormone, insulin, and somatostatin therapy of cancer cachexia [Ｊ]. Cancer, 1994; 73(5): 1499-1504.
35.	van Buul-Offers SC, Kooijman R. The role of growth hormone and insulin-like growth factors in the immune system [Ｊ]. Cell Mol Life Sci, 1998; 54(10): 1083-1094.

1. Kreymann KG. Early nutrition support in critical care: a European perspective [Ｊ]. Curr Opin Clin Nutr Metab Care, 2008; 11(2): 156-159.
2. Scurlock C, Mechanick JI. Early nutrition support in the intensive care unit: a US perspective [Ｊ]. Curr Opin Clin Nutr Metab Care, 2008; 11(2): 152-155.
3. 罗世成, 郭建辉, 朱军, 等. 胃肠道肿瘤患者术后早期肠内营养与肠外营养支持的随机对照研究 [Ｊ]. 中国普外基础与临床杂志, 2007; 14(3): 324-328.
4. Kudsk KA. Immunonutrition in surgery and critical care [Ｊ]. Annu Rev Nutr, 2006; 26: 463-479.
5. 张明鸣, 伍晓汀. 肠康复治疗和短肠综合征 [Ｊ]. 中国普外基础与临床杂志, 2007; 14(1): 117-119.
6. 陈先锋, 刘作金, 李旭宏, 等. TPN联合生长激素对胃肠道恶性肿瘤患者术后应激反应的抑制作用 [Ｊ]. 中国普外基础与临床杂志, 2006; 13(1): 45-47.
7. Akaza H, Matsuki K, Matsushima H, et al. Stimulatory effects of growth hormone on rat bladder carcinogenesis [Ｊ]. Cancer, 1991; 68(11): 2418-2421.
8. Maneatis T, Baptista J, Connelly K, et al. Growth hormone safety update from the National Cooperative Growth Study [Ｊ]. J Pediatr Endocrinol Metab, 2000; 13 Suppl 2: 1035-1044.
9. Tacke J, Bolder U, Herrmann A, et al. Long-term risk of gastrointestinal tumor recurrence after postoperative treatment with recombinant human growth hormone [Ｊ]. JPEN J Parenter Enteral Nutr, 2000; 24(3): 140-144.
10. Lang CH, Frost RA. Role of growth hormone, insulin-like growth factor-Ⅰ, and insulin-like growth factor binding proteins in the catabolic response to injury and infection [Ｊ]. Curr Opin Clin Nutr Metab Care, 2002; 5(3): 271-279.
11. Mller N, Jrgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects [Ｊ]. Endocr Rev, 2009; 30(2): 152-177.
12. Luo SM, Liang LJ, Lai JM. Effects of recombinant human growth hormone on remnant liver after hepatectomy in hepatocellular carcinoma with cirrhosis [Ｊ]. World J Gastroenterol, 2004; 10(9): 1292-1296.
13. Duska F, Fric M, Waldauf P, et al. Frequent intravenous pulses of growth hormone together with glutamine supplementation in prolonged critical illness after multiple trauma: effects on nitrogen balance, insulin resistance, and substrate oxidation [Ｊ]. Crit Care Med, 2008; 36(6): 1707-1713.
14. Hammarqvist F, Sandgren A, Andersson K, et al. Growth hormone together with glutamine-containing total parenteral nutrition maintains muscle glutamine levels and results in a less negative nitrogen balance after surgical trauma [Ｊ]. Surgery, 2001; 129(5): 576-586.
15. Jensen MB, Kissmeyer-Nielsen P, Laurberg S. Perioperative growth hormone treatment increases nitrogen and fluid balance and results in short-term and long-term conservation of lean tissue mass [Ｊ]. Am J Clin Nutr, 1998; 68(4): 840-846.
16. Jones CH, Newstead CG, Will EJ, et al. Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure [Ｊ]. Nephrol Dial Transplant, 1997; 12(7): 1406-1413.
17. Akenami FO, Koskiniemi M, Siimes MA, et al. Assessment of plasma fibronectin in malnourished Nigerian children [Ｊ]. J Pediatr Gastroenterol Nutr, 1997; 24(2): 183-188.
18. Heemskerk VH, Daemen MA, Buurman WA. Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in immunity and inflammation [Ｊ]. Cytokine Growth Factor Rev, 1999; 10(1): 5-14.
19. Berneis K, Keller U. Metabolic actions of growth hormone: direct and indirect [Ｊ]. Baillieres Clin Endocrinol Metab, 1996; 10(3): 337-352.
20. LeRoith D, Yakar S. Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1 [Ｊ]. Nat Clin Pract Endocrinol Metab, 2007; 3(3): 302-310.
21. Hayes VY, Urban RJ, Jiang J, et al. Recombinant human growth hormone and recombinant human insulin-like growth factor Ⅰ diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects [Ｊ]. J Clin Endocrinol Metab, 2001; 86(5): 2211-2219.
22. Mauras N, Haymond MW. Are the metabolic effects of GH and IGF-Ⅰ separable ? [Ｊ]. Growth Horm IGF Res, 2005; 15(1): 19-27.
23. Mauras N, Martinez V, Rini A, et al. Recombinant human insulin-like growth factor Ⅰ has significant anabolic effects in adults with growth hormone receptor deficiency: studies on protein, glucose, and lipid metabolism [Ｊ]. J Clin Endocrinol Metab, 2000; 85(9): 3036-3042.
24. Shimoda N, Tashiro T, Yamamori H, et al. Effects of gr-owth hormone and insulin-like growth factor-1 on protein metabolism, gut morphology, and cell-mediated immunity in burned rats [Ｊ]. Nutrition, 1997; 13(6): 540-516.
25. Nakhjavani M, Esteghamati A, Hamidi S, et al. Changes in growth hormone and insulin-like growth factor-Ⅰ levels in the acute stage after open heart surgery and at the time of discharge [Ｊ]. Exp Clin Endocrinol Diabetes, 2009; 117(8): 413-416.
26. Cao J, Luo SM, Liang L, et al. Effects of parenteral nutrition without and with growth hormone on growth hormone/insulin-like growth factor-1 axis after hepatectomy in hepatocellular carcinoma with liver cirrhosis [Ｊ]. JPEN J Parenter Enteral Nutr, 2007; 31(6): 496-501.
27. Inaba T, Saito H, Fukushima R, et al. Insulin-like growth factor 1 has beneficial effects, whereas growth hormone has limited effects on postoperative protein metabolism, gut integrity, and splenic weight in rats with chronic mild liver injury [Ｊ]. JPEN J Parenter Enteral Nutr, 1997; 21(2): 55-62.
28. Sevette A, Smith RC, Aslani A, et al. Does growth hormone allow more efficient nitrogen sparing in postoperative patients requiring parenteral nutrition? A double-blind, placebo-controlled randomised trial [Ｊ]. Clin Nutr, 2005; 24(6): 943-955.
29. Sánchez-Gómez M, Malmlf K, Mejía W, et al. Insulin-like growth factor-Ⅰ, but not growth hormone, is dependent on a high protein intake to increase nitrogen balance in the rat [Ｊ]. Br J Nutr, 1999; 81(2): 145-152.
30. Tacke J, Bolder U, Lhlein D. Improved cumulated nitrogen balance after administration of recombinant human growth hormone in patients undergoing gastrointestinal surgery [Ｊ]. Infusionsther Transfusionsmed, 1994; 21(1): 24-29.
31. Ng EH, Rock CS, Lazarus D, et al. Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model [Ｊ]. J Surg Res, 1991; 51(2): 99-105.
32. Wolf RF, Ng B, Weksler B, Burt M, et al. Effect of growth hormone on tumor and host in an animal model [Ｊ]. Ann Surg Oncol, 1994; 1(4): 314-320.
33. Torosian MH. Growth hormone and prostate cancer growth and metastasis in tumor-bearing animals [Ｊ]. J Pediatr Endocrinol, 1993; 6(1): 93-97.
34. Bartlett DL, Charland S, Torosian MH. Growth hormone, insulin, and somatostatin therapy of cancer cachexia [Ｊ]. Cancer, 1994; 73(5): 1499-1504.
35. van Buul-Offers SC, Kooijman R. The role of growth hormone and insulin-like growth factors in the immune system [Ｊ]. Cell Mol Life Sci, 1998; 54(10): 1083-1094.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Short-Term Administration of Growth Hormone on Serum IGF-1 and Nutritional Status in Patients after Gastrointestinal Surgery

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