Advances in Clinical and Experimental Medicine
2017, vol. 26, nr 2, March-April, p. 281–286
Publication type: original article
Serum leptin levels and GHR-d3/fl gene polymorphism in acromegalic patients with thyroid nodules
1 Department of Endocrinology and Metabolism, Pamukkale University, Denizli, Turkey
2 Department of Physiology, Pamukkale University, Denizli, Turkey
Background. Acromegaly is a rare and serious syndrome that is commonly associated with pituitary neoplasms. Thyroid multinodular disease is a common finding in acromegaly. Leptin is a polypeptide hormone, and studies have shown that it can increase cell proliferation and inhibit apoptosis.
Objectives. The aim of the study was to determine the relationship of serum leptin levels with certain blood parameters and determine if growth hormone receptor (GHR)-d3/fl gene polymorphism is associated with thyroid nodules in acromegalic patients.
Material and Methods. A total of 24 acromegalic patients with or without thyroid nodules were included in the study. Gene polymorphisms and blood parameters were examined.
Results. A marked increase was observed in serum leptin concentration in acromegalic patients with thyroid nodules compared to patients without them (p < 0.05). GH levels were lower in patients without nodules than in patients with nodules (p < 0.05). Blood glucose levels were higher in patients with nodules compared to those without them (p < 0.05), and the presence of thyroid nodules was associated with decreased blood low-density lipoprotein (LDL) levels compared to patients without nodules (p < 0.05). A significant relationship was observed between growth hormone receptor (GHR)-d3/fl gene polymorphism and leptin levels in acromegalic patients with thyroid nodules (p < 0.001).
Conclusion. These data from acromegalic patients indicate that thyroid nodules are associated with increased serum leptin, GH and blood glucose levels and with decreased LDL levels. GHR-d3/fl gene polymorphism status was strongly related to higher leptin levels.
thyroid, gene polymorphism, acromegaly, hormone, endocrinology
- Katznelson L. Alterations in body composition in acromegaly. Pituitary. 2009;12(2):136–142.
- Tunbridge WMG, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: The Whickham Survey. Clin Endocrinol (Oxf). 1977;7(6):481–493.
- Vander JB, Gaston EA, Dawber TR. The significance of nontoxic thyroid nodules. Final report of a 15-year study of the incidence of thyroid malignancy. Ann Intern Med. 1968;69(3):537–540.
- Tan GH, Gharib H. Thyroid incidentalomas: Management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med. 1997;126(3): 226–231.
- Gasperi M, Martino E, Manetti L, et al. Acromegaly study group of Italian Society of Endocrinology: Prevalence of thyroid diseases in patients with acromegaly: Results of an Italian multicenter study. J Endocrinol Invest. 2002;25(3):240–245.
- Herrmann BL, Baumann H, Janssen OE, Gorges R, Schmid KW, Mann K. Impact of disease activity on thyroid diseases in patients with acro-megaly: Basal evaluation and follow-up. Exp Clin Endocrinol Diabetes. 2004;112(5):225–230.
- Miyakawa M, Saji M, Tsushima T, Wakai K, Shizume K. Thyroid volume and serum thyroglobulin levels in patients with acromegaly: Correlation with plasma insulin-like growth factor 1 levels. J Clin Endocrinol Metab. 1988;67(5):973–978.
- Geelhoed-Duijvestijn PH, Bussemaker JK, Roelfsema F. Changes in basal and stimulated TSH and other parameters of thyroid function in acromegaly after transsphenoidal surgery. Acta Endocrinol. 1989;121(2):207–215.
- Roelfsema F, Frolich M. Pulsatile thyrotropin release and thyroid function in acromegalics before and during subcutaneous octreotide infusion. J Clin Endocrinol Metab. 1991;72 (1):77–82.
- Baldys-Waligorska A, Krzentowska A, Golkowski F, Sokolowsk G, Hubalewska-Dydejczyk A. The prevalence of benign and malignant neo-plasms in acromegalic patients. Endokrynol Pol. 2010;61(1): 29–34.
- Rowland NE, Morien A, Li BH. The physiology and brain mechanisms of feeding. Nutrition. 1996;12(9):626–639.
- Licinio J, Negrao AB, Mantzoros C, et al. Sex differences in circulating human leptin pulse amplitude: clinical implications. J Clin Endocrinol Metab. 1998;83(11):4140–4147.
- Lonnqvist F, Wennlund A, Arner P. Relationship between circulating leptin and peripheral fat distribution in obese subjects. Int J Obes Relat Metab Disord. 1997;21(4):255–260.
- EscobarMorreale HF, delRey FE, deEscobar GM. Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology. 1997;138(10);4485–4488.
- Santini F, Marsili A, Mammoli C, et al. Serum concentrations of adiponectin and leptin in patients with thyroid dysfunctions. J Clin Endocrinol Invest. 2004;27(2):RC5–RC7.
- Sesmilo G, Casamitjana R, Halperin I, Gomis R, Vilardell E. Role of thyroid hormones on serum leptin levels. Eur J Endocrinol. 1998;139(4):428–430.
- Sreenan S, Caro JF, Refetoff S. Thyroid dysfunction is not associated with alterations in serum leptin levels. Thyroid. 1997;7(3):407–409.
- Brauner R, Trivin C, Zerah M, et al. Diencephalic syndrome due to hypothalamic tumour: A model of the relationship between weight and puberty onset. J Clin Endocrinol Metab, 2006;91(7):2467–2473.
- Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol. 2006;207(1): 12–22.
- Hoda MR, Keely SJ, Bertelsen LS, Junger WG, Dharmasena D, Barrett KE. Leptin acts as a mitogenic and antiapoptotic factor for colonic cancer cells. Brit J Surg. 2007;94(3):346–354.
- Jaffe T, Schwartz B. Leptin promotes motility and invasiveness in human colon cancer cells by activating multiple signal-transduction path-ways. Int J Cancer. 2008;123(11):2543–2556.
- Li L, Gao Y, Zhang LL, He DL. Concomitant activation of the JAK/STAT3 and ERK1/2 signaling is involved in leptin-mediated proliferation of renal cell carcinoma Caki-2 cells. Cancer Biol Therapy. 2008;7(11):1787–1792.
- O’Brien SN, Welter BH. Price TM. Presence of leptin in breast cell lines and breast tumors. Bioch Bioph Res Co. 1999;259(3):695–698.
- Ribeiro R, Arauj A, Lopes C, Medeiros R. Immunoinflammatory mechanisms in lung cancer development: Is leptin a mediator? J Thorac Oncol. 2007;2(2):105–108.
- Mantzoros CS, Rosen HN, Greenspan SL, Flier JS, Moses AC. Short-term hyperthyroidism has no effect on leptin levels in man. J Clin Endocrinol Metab. 1997;82(2):497–499.
- Uddin S, Bavi P, Siraj AK, et al. Leptin-R and its association with PI3K/AKT signaling pathway in papillary thyroid carcinoma. Endocr Relat Can-cer. 2010;17(1):191–202.
- Valcavi R, Zini M, Peino R, Casanueva FF, Dieguez C. Influence of thyroid status on serum immunoreactive leptin levels. J Clin Endocrinol Metab. 1997;82(5):1632–1634.
- Toyoshiman MT, Castroneves LA, Costalonga EF, et al. Exon 3-deleted genotype of growth hormone receptor (GHRd3) positively influences IGF-1 increase at generation test in children with idiopathic short stature. Clin Endocrinol. 2007;67(4):500–504.
- Cheung NW, Boyages SC. The thyroid gland in acromegaly: An ultrasonographic study. Clin Endocrinol. 1997;46(5):545–549.
- Kasagi K, Shimatsu A, Miyamoto S, Misaki T, Sakahara H, Konishi J. Goiter associated with acromegaly: sonographic and scintigraphic findings of the thyroid gland. Thyroid. 1999;9(8):791–796.
- Freda PU. Current concepts in the biochemical assessment of the patient with acromegaly. Growth Horm IGF Res. 2003;13:171–184.
- Montefusco L, Filopanti M, Ronchi CL, et al. d3-Growth hormone receptor polymorphism in acromegaly: Effects on metabolic phenotype. Clin Endocrinol. 2010;72(5):661–667.
- Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary. 1999;2(1):29–41.
- Marzullo P, Cuocolo A, Ferone D, et al. Cardiac effect of thyrotoxicosis in acromegaly. J Clin Endocrinol Metab. 2000;85(4):1426–1432.
- Spada A, Lania A, Ballare E. G protein abnormalities in pituitary adenomas. Mol Cell Endocrinol. 1998;25(142):1–14.
- Bluher S, Kratzsch J, Kiess W. Insulin-like growth factor I, growth hormone and insulin in white adipose tissue. Best Pract Res Clin Endocrinol Metab. 2005;19(4):577–587.
- Damjanovic SS, Petakov MS, Raicevic S, et al. Serum leptin levels in patients with acromegaly before and after correction of hypersomato-tropism by trans-sphenoidal surgery. J Clin Endocrinol Metab. 2000;85(1):147–154.
- Bolanowski M, Milewicz A, Bidzinska B, Jedrzejuk D, Daroszewski J, Mikulski E. Serum leptin levels in acromegaly – a significant role for adi-pose tissue and fasting insulin/glucose ratio. Med Sci Monit. 2002;8:CR685–CR689.
- Paramo C, Fluiters E, de la Fuente J, Andrade A, Garcia-Mayor RV. Monitoring of treatment success in patients with acromegaly: The value of serum insulin-like growth factor binding protein-3 and serum leptin measurements in comparison to plasma insulin-like growth factor I determination. Metabolism. 2001;50(9):1117–1121.
- Parkinson C, Whatmore AJ, Yates AP, et al. The effect of pegvisomant-induced serum IGF-I normalization on serum leptin levels in patients with acromegaly. Clin Endocrinol (Oxf). 2003;59(2):168–174.
- Tan KC, Tso AW, Lam KS. Effect of Sandostatin LAR on serum leptin levels in patients with acromegaly. Clin Endocrinol (Oxf). 2001; 54(1):31–35.
- Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol. 1998;157(1): 75–79.
- Yoshida T, Momotani N, Hayashi M, Monkawa T, Ito K, Saruta T. Serum leptin concentrations in patients with thyroid disorders. Clin Endo-crinol. 1998;48(3):299–302.
- Bouloume A, Marumo T, Lafontan M, Busse R. Leptin induces oxidative stress in human endothelial cells. FASEB J. 1999;13(10):1231–1238.
- Yamagishi SI, Edelstein D, Du XL, Kaneda Y, Guzman M, Brownlee M. Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase. J Biol Chem. 2001;276(27):25096–25100.
- Holvoet P, Collen D. Oxidized lipoproteins in atherosclerosis and thrombosis. FASEB J. 1994;8(15):1279–1284.