Thyroid diseases and risk of non-thyroidal pathology

Cover Page


The review presents generalized epidemiological data on the prevalence of non-neoplastic thyroid pathology in developed and developing countries, in particular in regions with iodine deficiency and the influence of mass iodine prophylaxis on reducing the incidence and prevalence of thyroid diseases in these regions. The data on the prevalence of subclinical hypo- and hyperthyroidism are presented, where according to the averaged data 1 clinical manifestation of thyroid insufficiency accounted for 20 cases of unregistered subclinical hypothyroidism, and 1 case of identified thyroid hyperfunction accounted for 15 cases of subclinical hyperthyroidism. Methodological, clinical and social difficulties in studying the prevalence of thyroid pathology are described. The main nongenomic actions of thyroid hormones, which originated from extracellular domains of cell adhesion protein - integrin αVβ3, resulting in activation of mitogen-activated protein kinase, phosphatidylinositol-3 kinase and serine-threonine-protein kinases, are presented. The ultimate cell and tissue response to this stimulation is the activation of cell proliferation, angiogenesis, cell migration, and increased expression of tissue-specific proinflammatory genes, which ultimately lead to acceleration of the «cancer development and its natural history». Data from epidemiological studies, which established a correlation between thyroid status and incidence (prevalence) of malignant neoplasms, are given. As a result of population-based studies analysis it was demonstrated that long term hyperthyroidism increases the risk of developing malignant neoplasms of different localizations, in particular breast, ovarian, prostate and lung cancer.

R I Glushakov

Author for correspondence.
Military Medical Academy named after S.M. Kirov of Russian Federation Ministry of Defense

E V Kozyrko
Research Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakov; Saint Petersburg State Pediatric Medical University

I V Sobolev
Saint Petersburg Clinical Scientific and Practical Center of Modern Types of Medical Care (Oncology)

S A Ermolova
Military Medical Academy named after S.M. Kirov of Russian Federation Ministry of Defense

O V Vlaseva
Military Medical Academy named after S.M. Kirov of Russian Federation Ministry of Defense

A A Kuzin
Military Medical Academy named after S.M. Kirov of Russian Federation Ministry of Defense

N I Tapilskaya
Saint Petersburg State Pediatric Medical University

  • Глушаков Р.И., Власьева О.В., Соболев И.В. и др. Тиреоидный статус как прогностический маркёр в онкологии. Злокачеств. опухоли. 2015; 2 (13): 13-20.
  • Глушаков Р.И., Прошин С.Н., Тапильская Н.И. Роль тиреоидных гормонов в регуляции ангиогенеза, клеточной пролиферации и миграции. Гены и клетки. 2011; 6 (4): 26-33.
  • Aghini-Lombardi F., Antonangeli L., Martino E. et al. The spectrum of thyroid disorders in an iodinedeficient community: The pescopagano survey. J. Clin. Endocrinol. Metab. 1999; 84: 561-566.
  • Azizi F., Hedayati M., Rahmani M. et al. Reappraisal of the risk of iodineinduced hyperthyroidism: an epidemiological population survey. J. Endocrinol. Invest. 2005; 28: 23-29. doi: 10.1007/BF03345525.
  • Baltisberger B.L., Minder C.E., Bürgi H. Decrease of incidence of toxic nodular goitre in a region of Switzerland after full correction of mild iodine deficiency. Eur. J. Endocrinol. 1995; 132 (5): 546-549. doi: 10.1530/eje.0.1320546.
  • Barbero J.D., Gutiérrez-Zotes A., Montalvo I. et al. Free thyroxine levels are associated with cognitive abilities in subjects with early psychosis. Schizophr. Res. 2015; 166 (1-3): 37-42. doi: 10.1016/j.schres.2015.04.030.
  • Barker D.J., Phillips D.I. Current incidence of thyrotoxicosis and past prevalence of goitre in 12 British towns. Lancet. 1984; 2 (8402): 567-570. doi: 10.1016/S0140-6736(84)90776-1.
  • Belfiore A., Sava L., Runello F. et al. Solitary autonomously functioning thyroid nodules and iodine deficiency. J. Clin. Endocrinol. Metab. 1983; 56 (2): 283-287. doi: 10.1210/jcem-56-2-283.
  • Biondi B., Cooper D.C. The clinical significance of subclinical thyroid dysfunction. Endocr. Rev. 2008; 29: 76-131. doi: 10.1210/er.2006-0043.
  • Boekholdt S.M., Titan S.M., Wiersinga W.M. et al. Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk prospective population study. Clin. Endocrinol. (Oxf.). 2010; 72: 404-410. doi: 10.1111/j.1365-2265.2009.03640.x.
  • Canaris G.J., Manowitz N.R., Mayor G., Ridgway E.C. The Colorado thyroid disease prevalence study. Arch. Intern. Med. 2000; 160: 526-534. doi: 0.1001/archinte.160.4.526
  • Davis P.J., Glinsky G.V., Lin H.Y. et al. Cancer cell gene expression modulated from plasma membrane integrin αvβ3 by thyroid hormone and nanoparticulate tetrac. Front. Endocrinol. (Lausanne). 2015; 5: 240. doi: 10.3389/fendo.2014.00240.
  • Delitala A.P., Pilia M.G., Ferreli L. et al. Prevalence of unknown thyroid disorders in a Sardinian cohort. Eur. J. Endocrinol. 2014; 171 (1): 143-149. doi: 10.1530/EJE-14-0182.
  • Delshad H., Mehran L., Tohidi M. et al. The incidence of thyroid function abnormalities and natural course of subclinical thyroid disorders, Tehran, I.R. Iran. J. Endocrinol. Invest. 2012; 35 (5): 516-521.
  • Faber J., Selmer C. Cardiovascular disease and thyroid function. Front. Horm. Res. 2014; 43: 45-56.
  • Flynn R.V., MacDonald T.M., Morris A.D. et al. The thyroid epidemiology, audit and research study; thyroid dysfunction in the general population. J. Clin. Endocrinol. Metab. 2004; 89: 3879-3884. doi: 10.1210/jc.2003-032089.
  • Glaser N.S., Styne D.M. Predicting the likelihood of remission in children with Graves’ disease: a prospective, multicenter study. Pediatrics. 2008; 121 (3): e481-е488.
  • Goldman M.B., Monson R.R., Maloof F. Cancer mortality in women with thyroid disease. Cancer Res. 1990; 50 (8): 2283-2289.
  • Hellevik A.I., Asvold B.O., Bjøro T. et al. Thyroid function and cancer risk: a prospective population study. Cancer Epidemiol. Biomarkers Prev. 2009; 18 (2): 570-574. doi: 10.1158/1055-9965.EPI-08-0911.
  • Hetzel B.S. The nature and magnitude of the iodine deficiency disorders. In: Towards the global elimination of brain damage due to iodine deficiency. B. Hetzel et al. eds. New Delhi: Oxford University Press. 2004; 1-22.
  • Hollowell J.G., Staehling N.W., Flanders W.D. et al. Serum TSH, T4, 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: 489-499. doi: 10.1210/jcem.87.2.8182.
  • Kasagi K., Takahashi N., Inoue G. et al. Thyroid function in Japanese adults as assessed by a general health checkup system in relation with thyroid-related antibodies and other clinical parameters. Thyroid. 2009; 19 (9): 937-944. doi: 10.1089/thy.2009.0205.
  • Kim Y.A., Park Y.J. Prevalence and risk factors of subclinical thyroid disease. Endocrinol. Metab. (Seoul). 2014; 29 (1): 20-29. doi: 10.3803/EnM.2014.29.1.20.
  • Knudsen N., Jørgensen T., Rasmussen S. et al. The prevalence of thyroid dysfunction in a population with borderline iodine deficiency. Clin. Endocrinol. (Oxf.). 1999; 51: 361-367. doi: 10.1046/j.1365-2265.1999.00816.x.
  • Ko A.H., Wang F., Holly E.A. Pancreatic cancer and medical history in a population-based case-control study in the San Francisco Bay Area, California. Cancer Causes Control. 2007; 18 (8): 809-819. doi: 10.1007/s10552-007-9024-6.
  • Mondul A.M., Weinstein S.J., Bosworth T. et al. Circulating thyroxin, thyroid-stimulating hormone, and hypothyroid status and the risk of prostate cancer. PLoS One. 2012; 7 (10): e47730. doi: 10.1371/journal.pone.0047730.
  • Laurberg P., Pedersen K.M., Vestergaard H., Sigurdsson G. High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves’ disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland. J. Intern. Med. 1991; 229 (5): 415-420. doi: 10.1111/j.1365-2796.1991.tb00368.x.
  • Leese G.P., Flynn R.V., Jung R.T. et al. Increasing prevalence and incidence of thyroid disease in Tayside, Scotland: The Thyroid Epidemiology, Audit and Research Study (TEARS). Clin. Endocrinol. (Oxf.). 2008; 68: 311-316.
  • Li X., Yang X., Wang Y. et al. The prevalence and prognostic effects of subclinical thyroid dysfunction in dilated cardiomyopathy patients: a single-center cohort study. J. Card Fail. 2014; 20 (7): 506-512. doi: 10.1016/j.cardfail.2014.05.002.
  • Lytton S.D., Kahaly G.J. Bioassays for TSH-receptor autoantibodies: an update. Autoimmun. Rev. 2010; 10 (2): 116-122. doi: 10.1016/j.autrev.2010.08.018.
  • 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. 2008; 69: 687-696. doi: 10.1111/j.1365-2265.2008.03338.x.
  • Reinwein D., Benker G., König M.P. et al. The different types of hyperthyroidism in Europe. Results of a prospective survey of 924 patients. J. Endocrinol. Invest. 1988; 11 (3): 193-200. doi: 10.1007/BF03350134.
  • Robles-Osorio M.L., Zacarías-Rangel V., García-Solís P. et al. Prevalence of thyroid function test abnormalities and anti-thyroid antibodies in an open population in Central México. Rev. Invest. Clin. 2014; 66 (2): 113-120.
  • Selmer C., Olesen J.B., Hansen M.L. et al. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ. 2012; 345: e7895. doi: 10.1136/bmj.e7895.
  • Selmer C., Olesen J.B., Hansen M.L. et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J. Clin. Endocrinol. Metab. 2014; 99 (7): 2372-2382. doi: 10.1210/jc.2013-4184.
  • Shu X., Ji J., Li X. et al. Cancer risk in patients hospitalized for Graves’ disease: a population-based cohort study in Sweden. Br. J. Cancer. 2010; 102 (9): 1397-1399. doi: 10.1038/sj.bjc.6605624.
  • Stefan M., Wei C., Lombardi A. et al. Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. Proc. Natl. Acad. Sci. USA. 2014; 111 (34): 12 562-12 567.
  • Smith B.R., Sanders J., Furmaniak J. TSH receptor antibodies. Thyroid. 2007; 17 (10): 923-938. doi: 10.1089/thy.2007.0239.
  • Teng W., Shan Z., Teng X. et al. Effect of iodine intake on thyroid diseases in China. N. Engl. J. Med. 2006; 354: 2783-2793. doi: 10.1056/NEJMoa054022.
  • Tosovic A., Bondeson A.G., Bondeson L. et al. Triiodothyronine levels in relation to mortality from breast cancer and all causes: a population-based prospective cohort study. Eur. J. Endocrinol. 2013; 168 (4): 483-490. doi: 10.1530/EJE-12-0564.
  • Tunbridge W.M.G., Evered D.C., Hall R. et al. The spectrum of thyroid disease in the community: the Whickham survey. Clin. Endocrinol. 1977; 7: 481-493. doi: 10.1111/j.1365-2265.1977.tb01340.x.
  • Vanderpump M.P.J. The epidemiology of thyroid diseases. In: Braverman L.E., Utiger R.D. eds. Werner and Ingbar’s. The thyroid: A fundamental and clinical text. 9-th edn. Philadelphia: J.B. Lippincott-Raven. 2005; 398-406.
  • Wiersinga W.M. Thyroid autoimmunity. Endocr. Dev. 2014; 26: 139-157. doi: 10.1159/000363161.
  • Zimmermann M.B., Jooste P.L., Pandav C.S. Iodine-deficiency disorders. Lancet. 2008; 372: 1251-1262. doi: 10.1016/S0140-6736(08)61005-3.
  • Zhang Y., Chang Y., Ryu S. et al. Thyroid hormones and mortality risk in euthyroid individuals: the Kangbuk Samsung health study. J. Clin. Endocrinol. Metab. 2014; 99 (7): 2467-2476. doi: 10.1210/jc.2013-3832.


Abstract - 226

PDF (Russian) - 104

© 2017 Glushakov R.I., Kozyrko E.V., Sobolev I.V., Ermolova S.A., Vlaseva O.V., Kuzin A.A., Tapilskaya N.I.

Creative Commons License

This work is licensed
under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Свидетельство о регистрации СМИ ЭЛ № ФС 77-70434 от 20 июля 2017 года выдано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор)