Metabolic Syndrome, Thyroid Function and Autoimmunity - The PORMETS Study

Author(s): Luís Raposo*, Sandra Martins, Daniela Ferreira, João Tiago Guimarães, Ana Cristina Santos

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 19 , Issue 1 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: The prevalence of thyroid dysfunction and autoimmunity in the Portuguese population has not yet been estimated. However, the national prevalence of the metabolic syndrome remains high. The association of thyroid pathology with cardiovascular risk has been addressed but is still unclear. Our study aimed to evaluate the prevalence of thyroid dysfunction and autoimmunity and to assess the associations of thyroid-stimulating hormone and thyroid hormones and antibodies with metabolic syndrome, its components, and other possible determinants in a national sample.

Material and Methods: The present study included a subsample of 486 randomly selected participants from a nationwide cross-sectional study sample of 4095 adults. A structured questionnaire was administered on past medical history and socio-demographic and behavioural characteristics. Blood pressure and anthropometric measurements were collected, and the serum lipid profile, glucose, insulin, hs- CRP, TSH, FT4, FT3 and thyroid antibodies were measured.

Results: In our sample, the prevalence of hypothyroidism, hyperthyroidism and undiagnosed dysfunction was 4.9%, 2.5% and 72.2%, respectively. Overall, the prevalence of positivity for the thyroid peroxidase and thyroglobulin antibodies was 11.9% and 15.0%, respectively. A positive association was found between free triiodothyronine and metabolic syndrome (OR: 2.019; 95% CI: 1.196, 3.410). Additionally, thyroid peroxidase antibodies had a negative association with metabolic syndrome (OR: 0.465; 95% CI: 0.236, 0.917) and its triglyceride component (OR: 0.321; 95% CI: 0.124, 0.836).

Conclusion: The prevalence of undiagnosed thyroid dysfunction and autoimmunity was high. Thyroid peroxidase antibodies were negatively associated with metabolic syndrome and its triglyceride component, whereas the free triiodothyronine level was positively associated with metabolic syndrome.

Keywords: Metabolic syndrome, cardiovascular disease, thyroid antibodies, hypothyroidism, hyperthyroidism, thyroiditis, prevalence, portugal.

Garmendia, M.A.; Santos, P.S.; Guillén-Grima, F.; Galofré, J.C. The incidence and prevalence of thyroid dysfunction in Europe: A meta-analysis. J. Clin. Endocrinol. Metab., 2014, 99(3), 923-931.
Vanderpump, M.P. The epidemiology of thyroid disease. Br. Med. Bull., 2011, 99, 39-51.
van Tienhoven-Wind, L.J.; Dullaart, R.P. Low-normal thyroid function and the pathogenesis of common cardio-metabolic disorders. Eur. J. Clin. Invest., 2015, 45(5), 494-503.
Razvi, S.; Shakoor, A.; Vanderpump, M.; Weaver, J.U.; Pearce, S.H. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: A metaanalysis. J. Clin. Endocrinol. Metab., 2008, 93(8), 2998-3007.
Gencer, B.; Collet, T.H.; Virgini, V.; Auer, R.; Rodondi, N. Subclinical thyroid dysfunction and cardiovascular outcomes among prospective cohort studies. Endocr. Metab. Immune Disord. Drug Targets, 2013, 13(1), 4-12.
Aho, K.; Gordin, A.; Palosuo, T.; Punsar, S.; Valkeila, E.; Karvonen, M.; Inkovaara, J.; Pasternack, A. Thyroid autoimmunity and cardiovascular diseases. Eur. Heart J., 1984, 5(1), 43-46.
Chen, W.H.; Chen, Y.K.; Lin, C.L.; Yeh, J.H.; Kao, C.H. Hashimoto’s thyroiditis, risk of coronary heart disease, and L-thyroxine treatment: a nationwide cohort study. J. Clin. Endocrinol. Metab., 2015, 100(1), 109-114.
Raposo, L.; Severo, M.; Barros, H.; Santos, A.C. The prevalence of the metabolic syndrome in Portugal: The PORMETS study. BMC Public Health, 2017, 17(1), 555.
Iwen, K.A.; Schröder, E.; Brabant, G. Thyroid hormones and the metabolic syndrome. Eur. Thyroid J., 2013, 2(2), 83-92.
Delitala, A.P.; Fanciulli, G.; Pes, G.M.; Maioli, M.; Delitala, G. Thyroid hormones, metabolic syndrome and its components. Endocr. Metab. Immune Disord. Drug Targets, 2017, 17(1), 56-62.
Raposo, L.; Martins, S.; Ferreira, D.; Guimarães, J.T.; Santos, A.C. Vitamin D, parathyroid hormone and metabolic syndrome -The PORMETS study. BMC Endocr. Disord., 2017, 17(1), 71.
W.H.O, Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet, 2004, 363(9403), 157-163.
Friedewald, W.T.; Levy, R.I.; Fredrickson, D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem., 1972, 18, 499-502.
Matthews, D.R.; Hosker, J.P.; Rudenski, A.S.; Naylor, B.A.; Treacher, D.F.; Turner, R.C. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 1985, 28(7), 412-419.
Alberti, K.G.; Eckel, R.H.; Grundy, S.M.; Zimmet, P.Z.; Cleeman, J.I.; Donato, K.A.; Fruchart, J.C.; James, W.P.; Loria, C.M.; Smith, S.C. Jr. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation, 2009, 120(16), 1640-1645.
Pearce, S.H.S.; Brabant, G.; Duntas, L.H.; Monzani, F.; Peeters, R.P.; Razvi, S.; Wemeau, J-L. 2013 ETA guideline: Management of subclinical hypothyroidism. Eur. Thyroid J., 2013, 2(4), 215-228.
Biondi, B.; Bartalena, L.; Cooper, D.S.; Hegedüs, L.; Laurberg, P.; Kahaly, G.J. The 2015 European Thyroid Association guidelines on diagnosis and treatment of endogenous subclinical hyperthyroidism. Eur. Thyroid J., 2015, 4(3), 149-163.
Hollowell, J.G.; Staehling, N.W.; Flanders, W.D.; Hannon, W.H.; Gunter, E.W.; Spencer, C.A.; Braverman, L.E. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health And Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab., 2002, 87(2), 489-499.
Limbert, E.; Prazeres, S.; São Pedro, M.; Madureira, D.; Miranda, A.; Ribeiro, M.; Jacome de Castro, J.; Carrilho, F.; Oliveira, M.J.; Reguengo, H.; Borges, F. Thyroid Study Group of the Portuguese Endocrine Society. Iodine intake in Portuguese pregnant women: Results of a countrywide study. Eur. J. Endocrinol., 2010, 163(4), 631-635.
Pedersen, I.B.; Knudsen, N.; Jørgensen, T.; Perrild, H.; Ovesen, L.; Laurberg, P. Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: A prospective comparative register-based population survey. J. Clin. Endocrinol. Metab., 2002, 87(10), 4462-4469.
Soria, M.; Anson, M.; Escanero, J.F. Correlation analysis of exercise-induced changes in plasma trace element and hormone levels during incremental exercise in well-trained athletes. Biol. Trace Elem. Res., 2016, 170(1), 55-64.
Aggarwal, N.; Razvi, S. Thyroid and aging or the aging thyroid? An evidence-based analysis of the literature. J. Thyroid Res., 2013, 2013, 481287.
De Pergola, G.; Giorgino, F.; Benigno, R.; Guida, P.; Giorgino, R. Independent influence of insulin, catecholamines, and thyroid hormones on metabolic syndrome. Obesity (Silver Spring), 2008, 16(11), 2405-2411.
McGrogan, A.; Seaman, H.E.; Wright, J.W.; de Vries, C.S. The incidence of autoimmune thyroid disease: A systematic review of the literature. Clin. Endocrinol. (Oxf.), 2008, 69(5), 687-696.
McLeod, D.S.; Cooper, D.S. The incidence and prevalence of thyroid autoimmunity. Endocrine, 2012, 42(2), 252-265.
Merrill, S.J.; Mu, Y. Thyroid autoimmunity as a window to autoimmunity: an explanation for sex differences in the prevalence of thyroid autoimmunity. J. Theor. Biol., 2015, 375, 95-100.
Yang, L.; Lv, X.; Yue, F.; Wei, D.; Zhang, T. Subclinical hypothyroidism and the risk of metabolic syndrome: A meta-analysis of observational studies. Endocr. Res., 2016, 41(2), 158-165.
Eftekharzadeh, A.; Khamseh, M.E.; Farshchi, A.; Malek, M. The association between subclinical hypothyroidism and metabolic syndrome as defined by the ATP III Criteria. Metab. Syndr. Relat. Disord., 2016, 14(3), 137-144.
Åsvold, B.O.; Vatten, L.J.; Bjøro, T.; Bauer, D.C.; Bremner, A.; Cappola, A.R.; Ceresini, G.; den Elzen, W.P.; Ferrucci, L.; Franco, O.H.; Franklyn, J.A.; Gussekloo, J.; Iervasi, G.; Imaizumi, M.; Kearney, P.M.; Khaw, K.T.; Maciel, R.M.; Newman, A.B.; Peeters, R.P.; Psaty, B.M.; Razvi, S.; Sgarbi, J.A.; Stott, D.J.; Trompet, S.; Vanderpump, M.P.; Völzke, H.; Walsh, J.P.; Westendorp, R.G.; Rodondi, N. Thyroid Studies Collaboration. Thyroid function within the normal range and risk of coronary heart disease: An individual participant data analysis of 14 cohorts. JAMA Intern. Med., 2015, 175(6), 1037-1047.
Kim, B.J.; Kim, T.Y.; Koh, J.M.; Kim, H.K.; Park, J.Y.; Lee, K.U.; Shong, Y.K.; Kim, W.B. Relationship between serum free T4 (FT4) and metabolic syndrome (MS) and its components in healthy euthyroid subjects. Clin. Endocrinol. (Oxf.), 2009, 70(1), 152-160.
Wolffenbuttel, B.H.R.; Wouters, H.J.C.M.; Slagter, S.N.; van Waateringe, R.P.; Kobold, A.C.M.; van Vliet-Ostaptchouk, J.V.; Links, T.P.; van der Klauw, M.M. Thyroid function and metabolic syndrome in the population-based LifeLines cohort study. BMC Endocr. Disord., 2017, 7, 65.
Mehran, L.; Amouzegar, A.; Tohidi, M.; Moayedi, M.; Azizi, F. Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects. Thyroid, 2014, 24(11), 1566-1574.
Park, S.B.; Choi, H.C.; Joo, N.S. The relation of thyroid function to components of the metabolic syndrome in Korean men and women. J. Korean Med. Sci., 2011, 26, 540-545.
Roef, G.; Rietzschel, E.R.; Van Daele, C.M.; Taes, Y.E.; De Buyzere, M.L.; Gillebert, T.C.; Kaufman, J.M. Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects. Thyroid, 2014, 24(2), 223-231.
Kim, H.J.; Bae, J.C.; Park, H.K.; Byun, D.W.; Suh, K.; Yoo, M.H.; Kim, J.H.; Min, Y.; Kim, S.W.; Chung, J.H. Triiodothyronine levels are independently associated with metabolic syndrome in euthyroid middle-aged subjects. Endocrinol. Metab. (Seoul), 2016, 31(2), 311-319.
Dimitriadis, G.; Baker, B.; Marsh, H.; Mandarino, L.; Rizza, R.; Bergman, R.; Haymond, M. Gerich. Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans. Am. J. Physiol. Endocrinol. Metab., 1985, 248, E593-E601.
Rezzonico, J.; Niepomniszcze, H.; Rezzonico, M.; Pusiol, E.; Alberto, M.; Brenta, G. The association of insulin resistance with subclinical thyrotoxicosis. Thyroid, 2011, 21(9), 945-949.
Ferrannini, E.; Iervasi, G.; Cobb, J.; Ndreu, R.; Nannipieri, M. Insulin resistance and normal thyroid hormone levels: Prospective study and metabolomics analysis. Am. J. Physiol. Endocrinol. Metab., 2017, 312(5), E429-E436.
Reinehr, T. Obesity and thyroid function. Mol. Cell. Endocrinol., 2010, 316(2), 165-171.
Aydogan, B.İ.; Sahin, M. Adipocytokines in thyroid dysfunction. ISRN Inflamm., 2013, 2013, 646271.
Mullur, R.; Liu, Y-Y.; Brent, G.A. Thyroid hormone regulation of metabolism. Physiol. Rev., 2014, 94, 355-382.
Peixoto de Miranda, É.J.; Bittencourt, M.S.; Santos, I.S.; Lotufo, P.A.; Benseñor, I.M. Thyroid function and high-sensitivity C-reactive protein in cross-sectional results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil): Effect of adiposity and insulin resistance. Eur. Thyroid J., 2016, 5(4), 240-246.
Czarnywojtek, A.; Owecki, M.; Zgorzalewicz-Stachowiak, M.; Woliński, K.; Szczepanek-Parulska, E.; Budny, B.; Florek, E.; Waligórska-Stachura, J.; Miechowicz, I.; Baczyk, M.; Sawicka, N.; Dhir, S.; Ruchala, M. The role of serum C-reactive protein measured by high-sensitive method in thyroid disease. Arch. Immunol. Ther. Exp. (Warsz.), 2014, 62, 501-509.
Amouzegar, A.; Kazemian, E.; Gharibzadeh, S.; Mehran, L.; Tohidi, M.; Azizi, F. Association between thyroid hormones, thyroid antibodies and insulin resistance in euthyroid individuals: A population-based cohort. Diabetes Metab., 2015, 41(6), 480-488.
Agbaht, K.; Mercan, Y.; Kutlu, S.; Alpdemir, M.F.; Sezgin, T. Obesity with and without metabolic syndrome: Do vitamin D and thyroid autoimmunity have a role? Diabetes Res. Clin. Pract., 2014, 106(1), 27-34.
Siemińska, L.; Wojciechowska, C.; Walczak, K.; Borowski, A.; Marek, B.; Nowak, M.; Kajdaniuk, D.; Foltyn, W.; Kos-Kudla, B. Associations between metabolic syndrome, serum thyrotropin, and thyroid antibodies status in postmenopausal women, and the role of interleukin-6. Endokrynol. Pol., 2015, 66(5), 394-403.
Chen, W.H.; Chen, Y.K.; Lin, C.L.; Yeh, J.H.; Kao, C.H. Hashimoto’s thyroiditis, risk of coronary heart disease, and L-thyroxine treatment: a nationwide cohort study. J. Clin. Endocrinol. Metab., 2015, 100(1), 109-114.
Aho, K.; Gordin, A.; Palosuo, T.; Punsar, S.; Valkeila, E.; Karvonen, M.; Inkovaara, J.; Pasternack, A. Thyroid autoimmunity and cardiovascular diseases. Eur. Heart J., 1984, 5(1), 43-46.
Karch, A.; Thomas, S.L. Autoimmune thyroiditis as a risk factor for stroke. A historical cohort study. Neurology, 2014, 82(18), 1643-1652.
Wells, B.J.; Hueston, W.J. Are thyroid peroxidase antibodies associated with cardiovascular disease risk in patients with subclinical hypothyroidism? Clin. Endocrinol. (Oxf.), 2005, 62(5), 580-584.
Collet, T.H.; Bauer, D.C.; Cappola, A.R.; Asvold, B.O.; Weiler, S.; Vittinghoff, E.; Gussekloo, J.; Bremner, A.; den Elzen, W.P.; Maciel, R.M.; Vanderpump, M.P.; Cornuz, J.; Dörr, M.; Wallaschofski, H.; Newman, A.B.; Sgarbi, J.A.; Razvi, S.; Völzke, H.; Walsh, J.P.; Aujesky, D.; Rodondi, N. Thyroid Studies Collaboration. Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: An individual participant data analysis. J. Clin. Endocrinol. Metab., 2014, 99(9), 3353-3362.
Vanderpump, M.P.; Tunbridge, W.M.; French, J.M.; Appleton, D.; Bates, D.; Clark, F.; Grimley Evans, J.; Rodgers, H.; Tunbridge, F.; Young, E.T. The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community. Thyroid, 1996, 6(3), 155-160.
Iannello, S.; Cavaleri, A.; Milazzo, P.; Cantarella, S.; Belfiore, F. Low fasting serum triglyceride level as a precocious marker of autoimmune disorders. MedGenMed, 2003, 5(3), 20.
Prodam, F.; Filigheddu, N. Ghrelin gene products in acute and chronic inflammation. Arch. Immunol. Ther. Exp., 2014, 62(5), 369-384.
Altinova, A.E.; Toruner, F. KaraKoc, A.; Yetkin, I.; Ayvaz, G.; Cakir, N.; Arslan, M. Serum Ghrelin levels in patients with Hashimoto’s thyroiditis. Thyroid, 2006, 16(12), 1259-1264.
Biyikli, H.H.; Arduc, A.; Isik, S.; Ozuguz, U.; Caner, S.; Dogru, F.; Shorbagi, A.I.; Erden, G.; Berker, D.; Guler, S. Assessing the relationship between serum Ghrelin levels and metabolic parameters and autoimmunity in patients with euthyroid Hashimoto’s thyroiditis. Endocr. Pract., 2014, 20(8), 818-824.
Li, Z.; Xu, G.; Qin, Y.; Zhang, C.; Tang, H.; Yin, Y.; Xiang, X.; Li, Y.; Zhao, J.; Mulholland, M.; Zhang, W. Ghrelin promotes hepatic lipogenesis by activation of mTOR-PPARγ signaling pathway. PNAS., 2014, 111(36), 13163-13168.
Fröhlich, E.; Wahl, R. Thyroid Autoimmunity: Role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front. Immunol., 2017, 8, 521.
Stefanska, A.; Bergmann, K.; Sypniewska, G. Metabolic syndrome and menopause: Pathophysiology, clinical and diagnostic significance. Adv. Clin. Chem., 2015, 72, 1-75.

open access plus

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 01 August, 2018
Page: [75 - 83]
Pages: 9
DOI: 10.2174/1871530318666180801125258

Article Metrics

PDF: 40