Replacement GH Therapy After Bariatric Surgery in Patients With Very Severe Obesity

Summary

Obesity and obesity-related diseases have reached epidemic proportions in Western countries (1-3). Laparoscopic-adjustable silicone gastric banding (LASGB) is a purely restrictive operation that determine effective weight loss without inducing malabsorption (4-6). However, also after LASGB body weight loss is almost invariably associated with Free Fat Mass (FFM) loss, and the relevance of the FFM contribution to total energy expenditure is well-known (7-8). Different endocrine axes are reported to affect FFM. We previously reported that low levels of DHEA-S, an adrenal steroid with controversial anti-adipogenic and anti-atherogenic effects, are increased after the massive and sustainable weight loss induced by LASGB in severely obese premenopausal women and correlated with the higher post-operative FFM (9-10). It is also well known that GH/IGF-I axis exerts relevant effects on FFM and that reduced GH levels might increase Fat Mass (FM) and reduce FFM (11,12). Morbidly obese patients have a reduced GH secretion, generally reversible after weight loss (13-14). In a recent study currently in press, we reported that a persistent deficiency in the GH/IGF-I axis in very obese females is associated to lower decrease in FM after LASGB. Low IGF-I plasma levels have also been reported to be independent prognostic factors of liver steatosis and non-alcoholic steatohepatitis in morbidly obese patients (15) and ultrasound- measured hepatic left lobe volume might represent a reliable tool for the evaluation of liver involvement in obesity (16). GH deficiency (GHD) in adult patients is associated with an increase in FM and a parallel decrease in FFM (17). The severity of GDH is correlated to cardiovascular risk, body composition abnormalities and bone loss, and decreased left ventricular ejection fraction (18-20). GH therapy has been demonstrated to be effective in normalizing body composition, with beneficial effects up to a 2-years follow-up period (21-24). GH therapy has also been reported to be effective in sparing FFM during weight loss in obese patients and metabolic syndrome (25,26). However, these studies have some limitations due to the duration of the treatment and the lack of a preliminary evaluation of the GH/IGF-I axis secretory status in obese patients before the GH therapy. At present there are no data on the evaluation of the GH/IGF-I status before and after bariatric surgery and the effectiveness of recombinant GH treatment in very severe obese patients.

Timeline

Start

2007-07

Primary completion

2008-01

Completion

2008-03

Publications

• Background Groves T. Pandemic obesity in Europe. BMJ. 2006 Nov 25;333(7578):1081. doi: 10.1136/bmj.39038.449769.BE. Epub 2006 Nov 17.
• Background Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52. doi: 10.1016/S0140-6736(04)17018-9.
• Background Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab. 2006 Oct;17(8):328-36. doi: 10.1016/j.tem.2006.08.006. Epub 2006 Sep 7.
• Background DeMaria EJ. Bariatric surgery for morbid obesity. N Engl J Med. 2007 May 24;356(21):2176-83. doi: 10.1056/NEJMct067019. No abstract available.
• Background Kuzmak LI. A Review of Seven Years' Experience with Silicone Gastric Banding. Obes Surg. 1991 Dec;1(4):403-408. doi: 10.1381/096089291765560809.
• Background Angrisani L, Lorenzo M, Esposito G, Romano G, Puzziello A, Belfiore A, Santoro T, Roina G, Petito A, Falconi C, Tesauro B. Laparoscopic adjustable silicone gastric banding: preliminary results of the University of Naples experience. Obes Surg. 1997 Feb;7(1):19-21. doi: 10.1381/096089297765556178.
• Background Ravussin E, Burnand B, Schutz Y, Jequier E. Energy expenditure before and during energy restriction in obese patients. Am J Clin Nutr. 1985 Apr;41(4):753-9. doi: 10.1093/ajcn/41.4.753.
• Background Sergi G, Lupoli L, Busetto L, Volpato S, Coin A, Bertani R, Calliari I, Berton A, Enzi G. Changes in fluid compartments and body composition in obese women after weight loss induced by gastric banding. Ann Nutr Metab. 2003;47(3-4):152-7. doi: 10.1159/000070038.
• Background Savastano S, Valentino R, Belfiore A, De Luca N, de Alteriis A, Orio F Jr, Palomba S, Villani AM, Falconi C, Lupoli G, Lombardi G. Early carotid atherosclerosis in normotensive severe obese premenopausal women with low DHEA(S). J Endocrinol Invest. 2003 Mar;26(3):236-43. doi: 10.1007/BF03345163.
• Background Savastano S, Belfiore A, Guida B, Angrisani L, Orio F Jr, Cascella T, Milone F, Micanti F, Saldalamacchia G, Lombardi G, Colao A. Role of dehydroepiandrosterone sulfate levels on body composition after laparoscopic adjustable gastric banding in pre-menopausal morbidly obese women. J Endocrinol Invest. 2005 Jun;28(6):509-15. doi: 10.1007/BF03347238.
• Background Richelsen B, Pedersen SB, Kristensen K, Borglum JD, Norrelund H, Christiansen JS, Jorgensen JO. Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients. Metabolism. 2000 Jul;49(7):906-11. doi: 10.1053/meta.2000.6738.
• Background Umpleby AM, Russell-Jones DL. The hormonal control of protein metabolism. Baillieres Clin Endocrinol Metab. 1996 Oct;10(4):551-70. doi: 10.1016/s0950-351x(96)80711-7.
• Background Maccario M, Grottoli S, Procopio M, Oleandri SE, Rossetto R, Gauna C, Arvat E, Ghigo E. The GH/IGF-I axis in obesity: influence of neuro-endocrine and metabolic factors. Int J Obes Relat Metab Disord. 2000 Jun;24 Suppl 2:S96-9. doi: 10.1038/sj.ijo.0801289.
• Background Garcia-Galiano D, Sanchez-Garrido MA, Espejo I, Montero JL, Costan G, Marchal T, Membrives A, Gallardo-Valverde JM, Munoz-Castaneda JR, Arevalo E, De la Mata M, Muntane J. IL-6 and IGF-1 are independent prognostic factors of liver steatosis and non-alcoholic steatohepatitis in morbidly obese patients. Obes Surg. 2007 Apr;17(4):493-503. doi: 10.1007/s11695-007-9087-1.
• Background Santini F, Giannetti M, Mazzeo S, Fierabracci P, Scartabelli G, Marsili A, Valeriano R, Pucci A, Anselmino M, Zampa V, Vitti P, Pinchera A. Ultrasonographic evaluation of liver volume and the metabolic syndrome in obese women. J Endocrinol Invest. 2007 Feb;30(2):104-10. doi: 10.1007/BF03347407.
• Background 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 May;91(5):1621-34. doi: 10.1210/jc.2005-2227. Epub 2006 Apr 24.
• Background Colao A, Cerbone G, Pivonello R, Aimaretti G, Loche S, Di Somma C, Faggiano A, Corneli G, Ghigo E, Lombardi G. The growth hormone (GH) response to the arginine plus GH-releasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency. J Clin Endocrinol Metab. 1999 Apr;84(4):1277-82. doi: 10.1210/jcem.84.4.5605.
• Background Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G, Faggiano A, Corneli G, Ghigo E, Lombardi G. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab. 1999 Jun;84(6):1919-24. doi: 10.1210/jcem.84.6.5742.
• Background Colao A, Di Somma C, Cuocolo A, Filippella M, Rota F, Acampa W, Savastano S, Salvatore M, Lombardi G. The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study. J Clin Endocrinol Metab. 2004 Dec;89(12):5998-6004. doi: 10.1210/jc.2004-1042.
• Background Salomon F, Cuneo RC, Hesp R, Sonksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989 Dec 28;321(26):1797-803. doi: 10.1056/NEJM198912283212605.
• Background Vance ML, Mauras N. Growth hormone therapy in adults and children. N Engl J Med. 1999 Oct 14;341(16):1206-16. doi: 10.1056/NEJM199910143411607. No abstract available.
• Background Amato G, Mazziotti G, Di Somma C, Lalli E, De Felice G, Conte M, Rotondi M, Pietrosante M, Lombardi G, Bellastella A, Carella C, Colao A. Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections. J Clin Endocrinol Metab. 2000 Oct;85(10):3720-5. doi: 10.1210/jcem.85.10.6881.
• Background Johannsson G, Marin P, Lonn L, Ottosson M, Stenlof K, Bjorntorp P, Sjostrom L, Bengtsson BA. Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab. 1997 Mar;82(3):727-34. doi: 10.1210/jcem.82.3.3809.
• Background 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 Feb;89(2):695-701. doi: 10.1210/jc.2003-031264.
• Background NIH conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med. 1991 Dec 15;115(12):956-61.
• Results Savastano S, Di Somma C, Belfiore A, Guida B, Orio F Jr, Rota F, Savanelli MC, Cascella T, Mentone A, Angrisani L, Lombardi G, Colao A. Growth hormone status in morbidly obese subjects and correlation with body composition. J Endocrinol Invest. 2006 Jun;29(6):536-43. doi: 10.1007/BF03344144.
• Savastano S, Di Somma C, Angrisani L, Orio F, Longobardi S, Lombardi G, Colao A. Growth hormone treatment prevents loss of lean mass after bariatric surgery in morbidly obese patients: results of a pilot, open, prospective, randomized, controlled study. J Clin Endocrinol Metab. 2009 Mar;94(3):817-26. doi: 10.1210/jc.2008-1476. Epub 2008 Dec 9.

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