Insulin like growth factor 1 dependence in patients with metabolic syndrome of nodular pathology of the thyroid gland

Meri Rekvava, Lali Javashvili, Elene Giorgadze


Metabolic syndrome and nodular pathology of the thyroid gland is a widespread problem nowadays. Recently there has been a notable coincidence between metabolic syndrome and nodular pathology of thyroid gland. Hence, it is interesting to reveal the possible pathogenetic connection between these two diseases.
During the reviewing of articles in the Pubmed and Google Scholar database, the attention was attracted on the insulin-like growth factor system, which activates the cell growth and proliferation. Insulin-like growth factor system is activated during hyperinsulinemia, which alongside with insulin resistance and obesity forms basis for the development of metabolic syndrome.
Consequently, formed an idea to reveal the correlation between IGF 1 and thyroid nodular disease  in patients with metabolic syndrome.


Metabolic syndrome; Insulin like Growth Factor 1; Thyroid gland

Full Text:



Giorgadze ER, Goderidze TN, Asatiani KA. Intensity of metabolic syndrome in patients with different degrees of obesity. Georgian Med News. 2006 Jun;(135):99-101

J.Larry Jameson. Harrisons Endocrinology, second edition, 2010. chapter:4,17,18. ISBN: 978-0-07-174147-7, MHID: 0-07-174147-X.

Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595-607.

Rexford S. Ahima. Metabolic Basis of Obesity. Springer Science+Business Media. 2011 , Chapter 10. ISBN 978-1-4419-1606-8 e-ISBN 978-1-4419-1607-5, DOI 10.1007/978-1-4419-1607-5

Дедов ИИ, Мельниченко ГА, Фадеев ВВ. Эндокринология, издание второе, 2008:265-272, 414-415. ISBN:978-5-9704-0823-0.

Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med. 2003 Feb 24;163(4):427-36.

Henning Beck-Nielsen. The metabolic Syndrome, pharmacology and clinical aspects.Springer-Verlag Wien 2013. chapter 3. ISBN 978-3-7091-1330-1. ISBN 978-3-7091-1331-8 (eBook) DOI 10.1007/978-3-7091-1331-8.

Steiner DF, James DE. Cellular and molecular biology of the beta cell. Diabetologia. 1992 Dec;35 Suppl 2:S41-8.

Horwitz DL, Starr JI, Mako ME, Blackard WG, Rubenstein AH. Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. Journal of Clinical Investigation. 1975 Jun;55(6):1278-83.


Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. Journal of Clinical Investigation. 1988 Feb;81(2):442-8.

Ebina Y, Ellis L, Jarnagin K,et al. The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling., Cell. 1985 Apr;40(4):747-58.

Seino S, Seino M, Nishi S, Bell GI. Structure of the human insulin receptor gene and characterization of its promoter. Proceedings of the National Academy of Sciences of USA. 1989 Jan;86(1):114-8

Rosen OM. Banting lecture 1989. Structure and function of insulin receptors. Diabetes. 1989 Dec;38(12):1508-11

Kasuga M, Fujita-Yamaguchi Y, Blithe DL, Kahn CR. Tyrosine-specific protein kinase activity is associated with the purified insulin receptor. Proceedings of the National Academy of Sciences of USA. 1983 Apr;80(8):2137-41.

Vantaggiato C, Formentini I, Bondanza A, Bonini C, Naldini L, Brambilla R. ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially. Journal of biology. 2006 Jun 28;5(5):1.

Moller DE, Cohen O, Yamaguchi Y, Assiz R, Grigorescu F, Eberle A, Morrow LA, Moses AC, Flier JS. Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance. Diabetes. 1994 Feb 1;43(2):247-55.

Arioglu E, Andewelt A, Diabo C, Bell M, Taylor SI, Gorden P. Clinical course of the syndrome of autoantibodies to the insulin receptor (type B insulin resistance): a 28-year perspective. Medicine (Baltimore). 2002 Mar;81(2):87-100.

Pamela L. Lutsey, Lyn M. Steffen, June Stevens. Dietary Intake and the Development of the Metabolic Syndrome:The Atherosclerosis Risk in Communities Study.Circulation. 2008 Feb 12;117(6):754-61.

Oakes ND, Cooney GJ, Camilleri S, Chisholm DJ, Kraegen EW. Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding. Diabetes. 1997 Nov 1;46(11):1768-74.

Turner N, Cooney GJ, Kraegen EW, Bruce CR. Fatty acid metabolism, energy expenditure and insulin resistance in muscle. Journal of Endocrinology. 2014 Feb 1;220(2):T61-79.

Radziuk J. Homeostastic model assessment and insulin sensitivity/resistance. Diabetes. 2014 Jun 1;63(6):1850-4.

Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes care. 1998 Dec 1;21(12):2191-2

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.. Diabetologia. 1985 Jul;28(7):412-9.

Shanik MH, Xu Y, Škrha J, Dankner R, Zick Y, Roth J. Insulin Resistance and Hyperinsulinemia Is hyperinsulinemia the cart or the horse?. Diabetes care. 2008 Feb 1;31(Supplement 2):S262-8.

Jiali Wang, Silvana Obici, Kimyata Morgan, Nir Barzilai, Zhaohui Feng and Luciano Rossetti. Overfeeding Rapidly Induces Leptin and Insulin Resistance. Diabetes. 2001 Dec;50(12):2786-91.

Marceau P, Biron S, Hould FS, Marceau S, Simard S, Thung SN, Kral JG. Liver pathology and the metabolic syndrome X in severe obesity. Journal of Clinical Endocrinoly and Metabolism. 1999 May;84(5):1513-7.

Hanley AJ, Williams K, Festa A, Wagenknecht LE, D'Agostino RB Jr, Haffner SM. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes. 2005 Nov;54(11):3140-7.

Pasquali R, Gambineri A, Anconetani B, et al. The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen-progestagen treatment. Clinal Endocrinoly (Oxf). 1999 Apr;50(4):517-27.

Christian-Alexandre Castellano , Jean-Patrice Baillargeon, Scott Nugent, et al. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance. PLoS One. 2015 Dec 9;10(12):e0144116. doi: 10.1371/journal.pone.0144116.

Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. The Journal of Clinical Endocrinology & Metabolism. 2000 Mar;85(3):1151-8.

Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis and Rheumatism. 2007 Feb 15;57(1):109-15.

Zheng L, Yan W, Kong Y, Liang P, Mu Y. An epidemiological study of risk factors of thyroid nodule and goiter in Chinese women. International Journal of Clinical and Experimental Medicine. 2015 Jul 15;8(7):11379-87.

Cheserek M, Wu G, Shen L, Shi Y, Le G. Evaluation of the relationship between subclinical hypothyroidism and metabolic syndrome components among workers. International journal of occupational medicine and environmental health. 2014 Apr 1;27(2):175-87.

Waring AC, Rodondi N, Harrison S, Kanaya AM, Simonsick EM, Miljkovic I, Satterfield S, Newman AB, Bauer DC. Thyroid function and prevalent and incident metabolic syndrome in older adults: the Health, Ageing and Body Composition Study. Clinical endocrinology. 2012 Jun 1;76(6):911-8.

Lai Y, Wang J, Jiang F, Wang B, Chen Y, Li M, Liu H, Li C, Xue H, Li N, Yu J. The relationship between serum thyrotropin and components of metabolic syndrome. Endocrine journal. 2011;58(1):23-30.

Marc A. Fritz and Leon Speroff. Clinical Gynecolologic Endocrinology and Infertility, eight edition, 2011 by Lippincott Willians & Wilkins, a Wolters Kluwer business RG159.S62 2011 618.1--dc22.

D. LeRoith, Walter Zumkeller and Robert C. Baxter.Insulin Like Growth Factors. Kluwer academic/Plenum Publishers, ISBN: 0-306-47846-3 New York, U.S.A 2003

Jones JI, Clemmons DR. Insulin-Like Growth Factors and Their Binding Proteins: Biological Actions*. Endocrine reviews. 1995 Feb;16(1):3-4.

Rechler M.M. and Nissley S.P, Receptros for insulin –like growth factors . In Polypeptide hormone receptors, Posner, B.I., Ed., Marcel Dekker, New York, 1985, chap 9.

Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. The EMBO journal. 1986 Oct;5(10):2503.

Derek LeRoith, Mohan K. Raizada. Molecular and cellular biology of insulin like growth factors and their receptors, ISBN -13:978-1-4684-5687-5; e-ISBN-13:978-1-4684-5685-1; DOI:10.1007/978-1-4684-5685-1; 1989 Plenum Press, New York.

Chitnis MM, Yuen JS, Protheroe AS, Pollak M, Macaulay VM. The type 1 insulin-like growth factor receptor pathway. Clinical Cancer Research. 2008 Oct 15;14(20):6364-70.

LeRoith D, Werner H, Beitner-Johnson D, ROBERTS JR AT. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocrine reviews. 1995 Apr;16(2):143-63.

Kim JJ, Accili D. Signalling through IGF-I and insulin receptors: where is the specificity?. Growth Hormone & IGF Research. 2002 Apr 30;12(2):84-90.

Lee CY, Rechler MM. Purified rat acid-labile subunit and recombinant human insulin-like growth factor (IGF)-binding protein-3 can form a 150-kilodalton binary complex in vitro in the absence of IGFs. Endocrinology. 1995 Nov;136(11):4982-9.

Lee CY, Rechler MM. A major portion of the 150-kilodalton insulin-like growth factor-binding protein (IGFBP) complex in adult rat serum contains unoccupied, proteolytically nicked IGFBP-3 that binds IGF-II preferentially.

Endocrinology. 1995 Feb;136(2):668-78.

Lee CY, Rechler MM. Formation of 150-kDa binary complexes on insulin-like growth factor binding protein-3 and the acid-labile subunit in vitro and in vivo. Progress in growth factor research. 1995 Dec 31;6(2):241-51.

Baxter RC, Dai J. Purification and characterization of the acid-labile subunit of rat serum insulin-like growth factor binding protein complex. Endocrinology. 1994 Feb;134(2):848-52.

Cox GN, McDermott MJ, Merkel E,et al. Recombinant human insulin-like growth factor

Clemmons DR. Role of insulin-like growth factor binding proteins in controlling IGF actions. Molecular and cellular endocrinology. 1998 May 25;140(1):19-24.

Rajpathak SN, Gunter MJ, Wylie‐Rosett J, Ho GY, Kaplan RC, Muzumdar R, Rohan TE, Strickler HD. The role of insulin‐like growth factor‐I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes/metabolism research and reviews. 2009 Jan 1;25(1):3-12.

Rosenfeld RG, Hwa V, Wilson L, Lopez-Bermejo A, Buckway C, Burren C, Choi WK, Devi G, Ingermann A, Graham D, Minniti G. The insulin-like growth factor binding protein superfamily: new perspectives. Pediatrics. 1999 Oct 1;104(Supplement 5):1018-21.

Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. Journal of Biological Chemistry. 1978 Apr 25;253(8):2769-76.

Le Roith D. Insulin-like growth factors. New England Journal of Medicine. 1997 Feb 27;336(9):633-40.

Pérez R, García-Fernández M, Díaz-Sánchez M, Puche JE, Delgado G, Conchillo M, Muntané J, Castilla-Cortázar I. Mitochondrial protection by low doses of insulin-like growth factor-Ⅰin experimental cirrhosis. World J Gastroenterol. 2008 May 7;14(17):2731-9.

Puche JE, Garcia-Fernandez M, Muntane J, Rioja J, Gonzalez-Baron S, Castilla Cortazar I. Low doses of insulin-like growth factor-I induce mitochondrial protection in aging rats. Endocrinology. 2008 May;149(5):2620-7.

Garcia-Fernandez M, Delgado G, Puche JE, Gonzalez-Baron S, Castilla Cortazar I. Low doses of insulin-like growth factor I improve insulin resistance, lipid metabolism, and oxidative damage in aging rats. Endocrinology. 2008 May;149(5):2433-42.

García-Fernández M, Castilla-Cortázar I, Díaz-Sanchez M, Navarro I, Puche JE, Castilla A, Casares AD, Clavijo E, González-Barón S. Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis. BMC gastroenterology. 2005 Mar 3;5(1):7.

Castilla-Cortázar I, Pascual M, Urdaneta E, Pardo J, Puche JE, Vivas B, Díaz-Casares A, García M, Díaz-Sánchez M, Varela-Nieto I, Castilla A. Jejunal microvilli atrophy and reduced nutrient transport in rats with advanced liver cirrhosis: improvement by Insulin-like Growth Factor I. BMC gastroenterology. 2004 Jun 14;4(1):1.

Mirpuri E, Garcı́a-Trevijano ER, Castilla-Cortazar I, Berasain C, Quiroga J, Rodriguez-Ortigosa C, Mato JM, Prieto J, Avila MA. Altered liver gene expression in CCl 4-cirrhotic rats is partially normalized by insulin-like growth factor-I. The international journal of biochemistry & cell biology. 2002 Mar 31;34(3):242-52.

Muguerza B, Castilla-Cortázar I, Garcı́a M, Quiroga J, Santidrián S, Prieto J. Antifibrogenic effect in vivo of low doses of insulin-like growth factor-I in cirrhotic rats. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2001 May 31;1536(2):185-95.

Pascual M, Castilla-Cortazar I, Urdaneta E, Quiroga J, Garcia M, Picardi A, Prieto J. Altered intestinal transport of amino acids in cirrhotic rats: the effect of insulin-like growth factor-I. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2000 Aug 1;279(2):G319-24.

Castilla‐Cortazar I, Garcia M, Quiroga J, Diez N, Diez‐Caballero F, Calvo A, Diaz M, Prieto J. Insulin‐like growth factor‐I reverts testicular atrophy in rats with advanced cirrhosis. Hepatology. 2000 Mar 1;31(3):592-600.

Castilla-Cortazar IN, Garcia MA, Muguerza BE, Quiroga JO, Perez RA, Santidrian SA, Prieto JE. Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis. Gastroenterology. 1997 Nov 30;113(5):1682-91.

Clemmons DR. Involvement of insulin-like growth factor-I in the control of glucose homeostasis. Current opinion in pharmacology. 2006 Dec 31;6(6):620-5.

David R. Clemmons. The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J Clin Invest. 2004 Jan 1; 113(1): 25–27

D'Ercole AJ, Stiles AD, Underwood LE. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proceedings of the National Academy of Sciences. 1984 Feb 1;81(3):935-9.

Moses AC, Young SC, Morrow LA, O'Brien M, Clemmons DR. Recombinant human insulin-like growth factor I increases insulin sensitivity and improves glycemic control in type II diabetes. Diabetes. 1996 Jan 1;45(1):91-100.

Ueki K, Okada T, Hu J, Liew CW, Assmann A, Dahlgren GM, Peters JL,

Shackman JG, Zhang M, Artner I, Satin LS. Total insulin and IGF-I resistance in pancreatic β cells causes overt diabetes. Nature genetics. 2006 May 1;38(5):583-8.

Federici M, Porzio O, Lauro D, Borboni P, Giovannone B, Zucaro L, Hribal ML, Sesti G. Increased Abundance of Insulin/Insulin-Like Growth Factor-I Hybrid Receptors in Skeletal Muscle of Obese Subjects Is Correlated with In Vivo Insulin Sensitivity 1. The Journal of Clinical Endocrinology & Metabolism. 1998 Aug 1;83(8):2911-5.

Kulkarni RN, Brüning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR. Tissue-specific knockout of the insulin receptor in pancreatic β cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell. 1999 Feb 5;96(3):329-39.

Kulkarni RN, Holzenberger M, Shih DQ, Ozcan U, Stoffel M, Magnuson MA, Kahn CR. β-cell–specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter β-cell mass. Nature genetics. 2002 May 1;31(1):111-5.

Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC. Relationship between β-cell mass and fasting blood glucose concentration in humans. Diabetes care. 2006 Mar 1;29(3):717-8.

Holly JM, Amiel SA, Sandhu RR, Rees LH, Wass JA. The role of growth hormone in diabetes mellitus. Journal of Endocrinology. 1988 Sep 1;118(3):353-64.

Aguirre GA, Ita JR, Garza RG, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. Journal of translational medicine. 2016 Jan 6;14(1):1.

Speakman JR. Body size, energy metabolism and lifespan. Journal of Experimental Biology. 2005 May 1;208(9):1717-30.

Геннадиник АГ, Нелаева АА. Роль инсулиноподобного фактора роста-I в метаболизме, регуляции клеточного обновления и процессах старения. Ожирение и метаболизм. 2010(2).

Janket SJ, Manson JE, Sesso H, Buring JE, Liu S. A prospective study of sugar intake and risk of type 2 diabetes in women. Diabetes care. 2003 Apr 1;26(4):1008-15.

Saydah SH, Loria CM, Eberhardt MS, Brancati FL. Abnormal glucose tolerance and the risk of cancer death in the United States. American journal of epidemiology. 2003 Jun 15;157(12):1092-100.

BERSTEIN LM, TSYRLINA EV, VASILYEV DA, POROSHINA TE, KOVALENKO RG. The Phenomenon of the Switching of Estrogen Effects and Joker Function of Glucose: Similarities and Relation to Age‐Associated Pathology and Approaches to Correction. Annals of the New York Academy of Sciences. 2005 Dec 1;1057(1):235-46.

von Zglinicki T. Oxidative stress shortens telomeres. Trends in biochemical sciences. 2002 Jul 1;27(7):339-44.

Engin Basturk, metin kement, Dilek Yavuzer. The role of insulin-like growth factor 1 in development of benign and malignant thyroid nodules, Balkan medical journal 2012 jun; 29(2): 133-138.

Wasko R, Michalek K, Pacholska J, Obrepalska-Steplowska A, Gozdzicka-Jozefiak A, Sowinski J. Clinical significance of the insulin-likegrowth factor I gene promoter (P1) polymorphism in thyroid nodular disease. Neuroendocrinology Letters. 2005 Dec 1;26(6):699-703.

Modric T, Rajkumar K, Murphy LJ. Thyroid gland function and growth in IGF binding protein-1 transgenic mice. European journal of endocrinology. 1999 Aug 1;141(2):149-59.

Liu YJ, Qiang W, Liu XJ, Xu L, Guo H, Wu LP, Shi B. Association of insulin-like growth factor-1 with thyroid nodules. Oncology letters. 2011 Nov 1;2(6):1297-301.

Kimura T, Van Keymeulen A, Golstein J, Fusco A, Dumont JE, Roger PP. Regulation of thyroid cell proliferation by TSH and other factors: a critical evaluation of in vitro models. Endocrine reviews. 2001 Oct;22(5):631-56.

Welker MJ, Orlov D. Thyroid nodules. Am Fam Physician. 2003;67:559–566

Koh KB, Chang KW. Carcinoma in multinodular goitre. British journal of surgery. 1992 Mar 1;79(3):266-7.

Bradly DP, Reddy V, Prinz RA, Gattuso P. Incidental papillary carcinoma in patients treated surgically for benign thyroid diseases. Surgery. 2009 Dec 31;146(6):1099-104.

VAN DER LAAN BF, Freeman JL, Asa SL. Expression of growth factors and growth factor receptors in normal and tumorous human thyroid tissues. Thyroid. 1995 Feb;5(1):67-73.

Bechtner G, Schopohl D, Rafferzeder M, Gärtner R, Welsch U. Stimulation of thyroid cell proliferation by epidermal growth factor is different from cell growth induced by thyrotropin or insulin-like growth factor I. European journal of endocrinology. 1996 May 1;134(5):639-48.

Nakahashi K, Kitahori Y, Konishi N, Ohnishi T, Sugimura M, Hiasa Y. Establishment of a rat thyroid carcinoma cell line in vitro demonstrating high DNA synthesis in response to insulin-like growth factor I. Cancer letters. 1996 Mar 29;101(2):247-55.

Hsiao PJ, Tsai JH. Increased insulin-like growth factor-1 receptors in thyroid tissues of Graves' disease. Journal of the Formosan Medical Association= Taiwan yi zhi. 1993 Dec;93(11-12):925-32.

Chakravarty G, Santillan AA, Galer C, Adams HP, El-Naggar AK, Jasser SA, Mohsin S, Mondal D, Clayman GL, Myers JN. Phosphorylated insulin like growth factor-I receptor expression and its clinico-pathological significance in histologic subtypes of human thyroid cancer. Experimental Biology and Medicine. 2009 Apr 1;234(4):372-86.

Kimura T, Van Keymeulen A, Golstein J, Fusco A, Dumont JE, Roger PP.Regulation of thyroid cell proliferation by TSH and other factors: a critical evaluation of in vitro models. Endocrine reviews. 2001 Oct;22(5):631-56.

Gullu BE, Celik O, Gazioglu N, Kadioglu P. Thyroid cancer is the most common cancer associated with acromegaly. Pituitary. 2010 Sep 1;13(3):242-8.


  • There are currently no refbacks.


Become a REVIEWER 


ISSN: 2346-8491 (online)