Liver Fat Content in People with Pituitary Diseases: Influence of Serum IGF1 Levels

Abstract

Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome, and type 2 diabetes. NAFLD is also seen in patients with endocrinopathies. However, the relationship between endocrine diseases and the development of NAFLD is not well known. In this study, we set out to determine whether liver fat content (LFC) was associated with IGF1 levels in people with pituitary diseases (PD). Eighty-nine patients with pituitary diseases and 74 healthy controls were included in this study. LFC was measured using MRI. Hepatic steatosis was defined as LFC>5.5%. Patients with PD were older, and had a higher BMI than healthy controls. LFC was significantly higher in people with PD than in controls (6.5% vs. 3.2%; p<0.001). LFC was negatively associated with the IGF1 level. The prevalence of steatosis was higher in PD patients than in controls (36.3% vs. 14.8%; p=0.002). In multivariate analysis, which included patients and controls, the predictive variables for steatosis were age, BMI and IGF1 levels, whereas the presence of pituitary diseases and gender were not associated with steatosis. Our data showed that LFC was strongly associated with IGF1 levels. These results suggest that steatosis associated with PD is probably a consequence of a low IGF1 level in these patients.

Key words

steatosis - non-alcoholic fatty liver disease - IGF1 - pituitary diseases

• References

• 1 Cusi K. Nonalcoholic fatty liver disease in type 2 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 2009; 16: 141-149
• 2 Petit JM, Guiu B, Masson D, Duvillard L, Jooste V, Buffier P, Terriat B, Bouillet B, Brindisi MC, Loffroy R, Robin I, Hillon P, Cercueil JP, Verges B. Specifically PNPLA3-mediated accumulation of liver fat in obese patients with type 2 diabetes. J Clin Endocrinol Metab 2010; 95: E430-E436
• 3 Italian Association for the Study of the Liver (AISF) . AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions. Dig Liver Dis 2017; 49: 471-483
• 4 Hazlehurst JM, Tomlinson JW. Non-alcoholic fatty liver disease in common endocrine disorders. Eur J Endocrinol 2013; 169: R27-R37
• 5 Lonardo A, Carani C, Carulli N, Loria P. 'Endocrine NAFLD' a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis. J Hepatol 2006; 44: 1196-1207
• 6 Arturi F, Succurro E, Procopio C, Pedace E, Mannino GC, Lugarà M, Procopio T, Andreozzi F, Sciacqua A, Hribal ML, Perticone F, Sesti G. Nonalcoholic fatty liver disease is associated with low circulating levels of insulin-like growth factor-I. J Clin Endocrinol Metab 2011; 96: E1640-E1644
• 7 Xu L, Xu C, Yu C, Miao M, Zhang X, Zhu Z, Ding X, Li Y. Association between serum growth hormone levels and nonalcoholic fatty liver disease: A cross-sectional study. PLoS One 2012; 7: e44136
• 8 Lonardo A, Loria P, Leonardi F, Ganazzi D, Carulli N. Growth hormone plasma levels in nonalcoholic fatty liver disease. Am J Gastroenterol 2002; 97: 1071-1072
• 9 Hoffmann A, Bootsveld K, Gebhardt U, Daubenbüchel AM, Sterkenburg AS, Müller HL. Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma. Eur J Endocrinol 2015; 173: 389-397
• 10 Guiu B, Petit JM, Loffroy R, Ben Salem D, Aho S, Masson D, Hillon P, Krause D, Cercueil JP. Quantification of liver fat content: Comparison of triple-echo chemical shift gradient-echo imaging and in vivo proton MR spectroscopy. Radiology 2009; 250: 95-102
• 11 Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 1387-1395
• 12 Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL. Magnetic resonance spectroscopy to measure hepatic triglyceride content: Prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 2005; 288: E462-E468
• 13 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
• 14 Meienberg F, Yee M, Johnston D, Cox J, Robinson S, Bell JD, Thomas EL, Taylor-Robinson SD, Godsland I. Liver fat in adults with GH deficiency: Comparison to matched controls and the effect of GH replacement. Clin Endocrinol 2016; 85: 76-84
• 15 Reyes-Vidal CM, Mojahed H, Shen W, Jin Z, Arias-Mendoza F, Fernandez JC, Gallagher D, Bruce JN, Post KD, Freda PU. Adipose tissue redistribution and ectopic lipid deposition in active acromegaly and effects of surgical treatment. J Clin Endocrinol Metab 2015; 100: 2946-2955
• 16 Szendroedi J, Zwettler E, Schmid AI, Chmelik M, Pacini G, Kacerovsky G, Smekal G, Nowotny P, Wagner O, Schnack C, Schernthaner G, Klaushofer K, Roden M. Reduced basal flux of skeletal muscle in patients with previous acromegaly. PLoS One 2008; 3: e3958
• 17 Takahashi Y, Iida K, Takahashi K, Yoshioka S, Fukuoka H, Takeno R, Imanaka M, Nishizawa H, Takahashi M, Seo Y, Hayashi Y, Kondo T, Okimura Y, Kaji H, Kitazawa R, Kitazawa S, Chihara K. Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency. Gastroenterology 2007; 132: 938-943
• 18 Matsumoto R, Fukuoka H, Iguchi G, Nishizawa H, Bando H, Suda K, Takahashi M, Takahashi Y. Long-term effects of growth hormone replacement therapy on liver function in adult patients with growth hormone deficiency. Growth Horm IGF Res 2014; 24: 174-179
• 19 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
• 20 Laron Z, Ginsberg S, Webb M. Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion – preliminary report. Growth Horm IGF Res 2008; 18: 434-438
• 21 Cordoba-Chacon J, Majumdar N, List EO, Diaz-Ruiz A, Frank SJ, Manzano A, Bartrons R, Puchowicz M, Kopchick JJ, Kineman RD. Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice. Diabetes 2015; 64: 3093-3103