Metabolic Parameters and Nonalcoholic Fatty Liver Disease in Hypopituitary Men

Abstract

Patients with hypopituitarism have the feature of metabolic syndrome, including central obesity, insulin resistance, and dyslipidemia. Because metabolic syndrome, including insulin resistance, is the main pathogenesis of the development of nonalcoholic fatty liver disease (NAFLD), we considered that patients diagnosed with hypopituitarism have an increased risk of developing NAFLD. We compared control subjects and hypopituitary men in metabolic parameters and the frequency of fatty liver on abdominal ultrasonography, and analyzed associating factors with the severity of the fatty liver in patients with hypopituitarism. 34 male patients with hypopituitarism and 40 age and sex-matched control subjects were included. The frequency of fatty liver on abdominal ultrasonography was significantly higher in hypopituitary men compared to control subjects (32.5% vs. 70.6%, p=0.001). Ln CRP and free fatty acids were significantly elevated in hypopituitary patients with fatty liver compared to patients without fatty liver. Ln GH was significantly lower in hypopituitary patients with fatty liver. The severity of fatty liver on abdominal ultrasonography correlated with negatively Ln GH, after adjusting for the BMI effect (p=0.020). There is a difference only between the severe fatty liver group and normal liver group in the analysis of the mean Ln GH level between 4 groups according to the severity of fatty liver (p=0.036). In conclusion, NAFLD is more common in hypopituitary patients than control subject. Severe growth hormone deficiency in hypopituitarism was associated with the severe degree of hepatic steatosis in NAFLD.

Key words

hypopituitarism - fatty liver - hepatic steatosis - nonalcoholic steatohepatitis - metabolic syndrome - growth hormone

References

• 1 Angulo P. Nonalcoholic fatty liver disease.  N Engl J Med. 2002;  346 1221-1231
• 2 Jou J, Choi S, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease.  Semin Liver Dis. 2008;  28 370-379
• 3 Lewis JR, Mohanty SR. Nonalcoholic fatty liver disease: a review and update.  Dig Dis Sci;. 2010;  55 560-578
• 4 Day CP. Natural history of NAFLD: remarkably benign in the absence of cirrhosis.  Gastroenterology. 2005;  129 375-378
• 5 Tarantino G, Conca P, Riccio A, Tarantino M, Di Minno MN, Chianese D, Pasanisi F, Contaldo F, Scopacasa F, Capone D. Enhanced serum concentrations of transforming growth factor-beta1 in simple fatty liver: is it really benign?.  J Transl Med. 2008;  6 72
• 6 Sesmilo G, Miller KK, Hayden D, Klibanski A. Inflammatory cardiovascular risk markers in women with hypopituitarism.  J Clin Endocrinol Metab. 2001;  86 5774-5781
• 7 Bohdanowicz-Pawlak A, Szymczak J, Bladowska J, Bednarek-Tupikowska G, Bidzińska B, Milewicz A. Risk factors of cardiovascular disease in GH-deficient adults with hypopituitarism: a preliminary report.  Med Sci Monit. 2006;  12 CR75-CR80
• 8 Attanasio AF, Mo D, Erfurth EM, Tan M, Ho KY, Kleinberg D, Zimmermann AG, Chanson P. Prevalence of metabolic syndrome in adult hypopituitary growth hormone (GH)-deficient patients before and after GH replacement.  J Clin Endocrinol Metab. 2010;  95 74-81
• 9 Abs R, Feldt-Rasmussen U, Mattsson AF, Monson JP, Bengtsson B, Gth MI, Wilton P, Koltowska-Hggstrm M. Determinants of cardiovascular risk in 2 589 hypopituitary GH-deficient adults – a KIMS database analysis.  Europ J Endocrinol. 2006;  155 79-90
• 10 Beshyah SA, Johnston DG. Cardiovascular disease and risk factors in adults with hypopituitarism.  Clin Endocrinol. 1999;  50 1-15
• 11 Nyenwe EA, Williamson-Baddorf S, Waters B, Wan JY, Solomon S. Nonalcoholic Fatty liver disease and metabolic syndrome in hypopituitary patients.  Am J Med Sci. 2009;  338 190-195
• 12 Adams LA, Feldstein A, Lindor KD, Angulo P. Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction.  Hepatology. 2004;  39 909-914
• 13 Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis.  Br Med J (Clinical research ed. 1981). 1986;  292 13-15
• 14 Ma X, Holalkere NS, Kambadakone RA, Mino-Kenudson M, Hahn PF, Sahani DV. Imaging-based quantification of hepatic fat: methods and clinical applications.  Radiographics. 2009;  29 1253-1277
• 15 Fan J, Peng Y. Metabolic syndrome and non-alcoholic fatty liver disease: Asian definitions and Asian studies.  Hepatobiliary Pancreat Dis Int. 2007;  6 572-578
• 16 Boppidi H, Daram SR. Nonalcoholic fatty liver disease: hepatic manifestation of obesity and the metabolic syndrome.  Postgrad Med. 2008;  120 E01-E07
• 17 Abdu TA, Neary R, Elhadd TA, Akber M, Clayton RN. Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities.  Clin Endocrinol. 2001;  55 209-216
• 18 Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Tani S, Goto M. Prevalence of fatty liver in a general population of Okinawa, Japan.  Jap J Med. 1988;  27 142-149
• 19 Arun J, Clements RH, Lazenby AJ, Leeth R, Abrams GA. The prevalence of nonalcoholic steatohepatitis is greater in morbidly obese men compared to women.  Obes Surg. 2006;  16 1351-1358
• 20 Weston SR, Leyden W, Murphy R, Bass NM, Bell BP, Manos MM, Terrault NA. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease.  Hepatology. 2005;  41 372-379
• 21 Parini P, Angelin B, Rudling M. Cholesterol and lipoprotein metabolism in aging: reversal of hypercholesterolemia by growth hormone treatment in old rats.  Arterioscler Thromb Vasc Biol. 1999;  19 832-839
• 22 Seki S, Kitada T, Sakaguchi H. Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases.  Hepatol Res. 2005;  33 132-134
• 23 Tamura S, Shimomura I. Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease.  J Clin Invest. 2005;  115 1139-1142
• 24 de Almeida IT, Cortez-Pinto H, Fidalgo G, Rodrigues D, Camilo ME. Plasma total and free fatty acids composition in human non-alcoholic steatohepatitis.  Clin Nut. 2002;  21 219-223
• 25 Videla LA, Tapia G, Rodrigo R, Pettinelli P, Haim D, Santibaez C, Araya AV, Smok G, Csendes A, Gutierrez L, Rojas J, Castillo J, Korn O, Maluenda F, Daz JC, Rencoret G, Poniachik J. Liver NF-kappaB and AP-1 DNA binding in obese patients.  Obesity. 2009;  17 973-979
• 26 Crespo J, Cayn A, Fernndez-Gil P, Hernndez-Guerra M, Mayorga M, Domnguez-Dez A, Fernndez-Escalante JC, Pons-Romero F. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients.  Hepatology. 2001;  34 1158-1163
• 27 Park SH, Kim BI, Yun JW, Kim JW, Park DI, Cho YK, Sung IK, Park CY, Sohn CI, Jeon WK, Kim H, Rhee EJ, Lee WY, Kim SW. Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men.  J Gastroenterol Hepatol. 2004;  19 694-698
• 28 Riquelme A, Arrese M, Soza A, Morales A, Baudrand R, Prez-Ayuso RM, Gonzlez R, Alvarez M, Hernndez V, Garca-Zattera MJ, Otarola F, Medina B, Rigotti A, Miquel JF, Marshall G, Nervi F. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-reactive protein in Hispanics.  Liver Int. 2009;  29 82-88
• 29 McConnell EM, Atkinson AB, Ennis C, Hadden DR, McCance DR, Sheridan B, Bell PM. The effects on insulin action in adult hypopituitarism of recombinant human GH therapy individually titrated for six months.  J Clin Endocrinol Metab. 2001;  86 5342-5347
• 30 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

1 These authors contributed equally to this work and should both be considered as first authors.

Correspondence