Non-specific rheumatic manifestations in patients with Hashimoto’s thyroiditis: a pilot cross-sectional study
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Hashimoto’s thyroiditis (HT) is often associated with rheumatic disorders (arthritis, etc.), but many HT patients report non-specific rheumatic signs and symptoms in the absence of clinically evident rheumatic diseases. Aim of this study was to evaluate the prevalence of non-specific rheumatic manifestations (RMs) in HT subjects without classified autoimmune comorbidities.
500 HT patients (467 F, 33 M; median age 41 years, range 14–69) and 310 age- and sex-matched controls, consecutively referred to the Endocrine Unit of Messina University Hospital, were evaluated for non-specific RMs. None took l-thyroxine. Exclusion criteria: autoimmune comorbidities, infectious, and/or inflammatory diseases, history of neoplasia, BMI > 30 kg/m2.
In our HT cohort, 100 patients (20%) complained of one or more RMs, vs 21 controls (6.8%; P < 0.001). There were minimal differences between the manifestations recorded in the two groups, the most common being polyarthralgias and myalgias/fibromyalgia, but non-specific RMs occurred threefold more in HT patients. Comparing HT patients with RMs (96 F and 4 M) with those affected by HT alone, female sex was prevalent (F:M ratio 24:1 vs 5:1) with higher age at diagnosis (median 43 vs 37 years; P < 0.001). HT patients with RMs (62%) were mostly euthyroid (median TSH 2.0 µIU/L) and only 7% overtly hypothyroid, discouraging a possible causal relationship between thyroid dysfunction per se and RMs.
A significant percentage of HT patients complains of non-specific rheumatic signs and symptoms, in the absence of other diagnosed systemic comorbidities and regardless of thyroid functional status, deserving careful evaluation and prolonged follow-up.
KeywordsAutoimmune diseases Hashimoto’s thyroiditis Thyroid autoimmunity Rheumatic manifestations Connective tissue diseases
This work was not supported by any grant.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent from each subject and Ethics Committee approval were obtained.
No animals were used for this study.
- 1.McLeod DS, Cooper DS (2012) The incidence and prevalence of thyroid autoimmunity. Endocrine 42(2):252–265Google Scholar
- 2.Ruggeri RM, Giuffrida G, Campennì A (2018) Autoimmune endocrine diseases. Minerva Endocrinol 43(3):305–322Google Scholar
- 3.Ajjan RA, Weetman AP (2015) The pathogenesis of Hashimoto’s thyroiditis: further developments in our understanding. Horm Metab Res 47(10):702–710Google Scholar
- 4.Effraimidis G, Wiersinga WM (2014) Mechanisms in endocrinology: autoimmune thyroid disease: old and new players. Eur J Endocrinol 170(6):241–252Google Scholar
- 5.Giovinazzo S, Vicchio TM, Certo R, Alibrandi A, Palmieri O, Campenni A, Cannavò S, Trimarchi F, Ruggeri RM (2017) Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in Hashimoto’s thyroiditis. Endocrine 55(2):599–606Google Scholar
- 6.Ruggeri RM, Vicchio TM, Cristani M, Certo R, Caccamo D, Giovinazzo Alibrandi A, Saija SA, Campennì A, Trimarchi F et al (2016) Oxidative stress and advanced glycation end products in Hashimoto’s thyroiditis. Thyroid 26(4):504–511Google Scholar
- 7.Rosser EC, Mauri C (2016) A clinical update on the significance of the gut microbiota in systemic autoimmunity. J Autoimmun 74:85–93Google Scholar
- 8.de Carvalho JF, Pereira RM, Shoenfeld Y (2009) The mosaic of autoimmunity: the role of environmental factors. Front Biosci (Elite Ed) 1:501–509Google Scholar
- 9.Weetman AP (2011) Diseases associated with thyroid autoimmunity: explanations for the expanding spectrum. Clin Endocrinol (Oxf) 74(4):411–418Google Scholar
- 10.Jabrocka-Hybel A, Skalniak A, Piątkowski J, Turek-Jabrocka R, Vyhouskaya P, Ludwig-Słomczyńska A, Machlowska J, Kapusta P, Maecki M, Pach D et al (2018) How much of the predisposition to Hashimoto’s thyroiditis can be explained based on previously reported associations? J Endocrinol Invest 41:1409–1416Google Scholar
- 11.Boelaert K, Newby PR, Simmonds MJ, Holder RL, Carr-Smith JD, Heward JM, Manji N, Allahabadia A, Armitage M, Chatterjee KV et al (2010) Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med 123(2):183 e1–9Google Scholar
- 12.Biro E, Szekanecz Z, Czirjak L, Danko K, Kiss E, Szabo NA, Szucs G, Zeher M, Bodolay E, Szegedi G et al (2006) Association of systemic and thyroid autoimmune diseases. Clin Rheumatol 25(2):240–245Google Scholar
- 13.Ruggeri RM, Trimarchi F, Giuffrida G, Certo R, Cama E, Campenni A, Alibrandi A, De Luca F, Wasniewska M (2017) Autoimmune comorbidities in Hashimoto’s thyroiditis: different patterns of association in adulthood and childhood/adolescence. Eur J Endocrinol 176(2):133–141Google Scholar
- 14.Utiyama SRR, De Bem RS, Skare TL, De Carvalho GA, Teixeira LM, Bertolazo M, Ioshii SO, Nisihara R (2018) Anti-parietal cell antibodies in patients with autoimmune thyroid diseases. J Endocrinol Invest 41(5):523–529Google Scholar
- 15.Acay A, Ulu MS, Ahsen A, Eroglu S, Ozuguz U, Yuksel S, Acarturk G (2014) Assessment of thyroid disorders and autoimmunity in patients with rheumatic diseases. Endocr Metab Immune Disord Drug Targets 14(3):182–186Google Scholar
- 16.Soy M, Guldiken S, Arikan E, Altun BU, Tugrul A (2007) Frequency of rheumatic diseases in patients with autoimmune thyroid disease. Rheumatol Int 27(6):575–577Google Scholar
- 17.Tektonidou MG, Anapliotou M, Vlachoyiannopoulos P, Moutsopoulos HM (2004) Presence of systemic autoimmune disorders in patients with autoimmune thyroid diseases. Ann Rheum Dis 63(9):1159–1161Google Scholar
- 18.Bagnato GL, Roberts WN, Fiorenza A, Arcuri C, Certo R, Trimarchi F, Ruggeri RM, Bagnato GF (2016) Skin fibrosis correlates with circulating thyrotropin levels in systemic sclerosis: translational association with Hashimoto’s thyroiditis. Endocrine 51:291–297Google Scholar
- 19.Yavne Y, Tiosano S, Watad A, Comaneshter D, Shoenfeld Y, Cohen AD, Amital H (2017) Association between giant cell arteritis and thyroid dysfunction in a “real life” population. Endocrine 57(2):241–246Google Scholar
- 20.Watad A, Mahroum N, Whitby A, Gertel S, Comaneshter D, Cohen AD, Amital H (2016) Hypothyroidism among SLE patients: case-control study. Autoimmun Rev 15(5):484–486Google Scholar
- 21.Liu YC, Lin WY, Tsai MC, Fu LS (2017) Systemic lupus erythematosus and thyroid disease—experience in a single medical center in Taiwan. J Microbiol Immunol Infect 52(3):480–486Google Scholar
- 22.Punzi L, Ostuni PA, Betterle C, De Sandre P, Botsios C, Gambari PF (1996) Thyroid gland disorders in primary Sjögren’s syndrome. Rev Rhum Engl Ed 63(11):809–814Google Scholar
- 23.Punzi L, Michelotto M, Pianon M, Bertazzolo N, Fagiolo U, Betterle C, Vettor R, Todesco S (1997) Clinical, laboratory and immunogenetic aspects of arthritis associated with chronic lymphocytic thyroiditis. Clin Exp Rheumatol 15(4):373–380Google Scholar
- 24.Becker KL, Ferguson RH, McConahey WM (1963) The connective-tissue diseases and symptoms associated with Hashimoto’s thyroiditis. N Engl J Med 268:277–280Google Scholar
- 25.Golding DN (1993) Rheumatism and the thyroid. J R Soc Med 86(3):130–132Google Scholar
- 26.Chakravarty SD, Markerson JA (2013) Rheumatic manifestations of endocrine disease. Curr Opin Rheumatol 25:37–43Google Scholar
- 27.Punzi L, Betterle C (2004) Chronic autoimmune thyroiditis and rheumatic manifestations. Jt Bone Spine 71(4):275–283Google Scholar
- 28.Tagoe CE (2015) Rheumatic symptoms in autoimmune thyroiditis. Curr Rheumatol Rep 17(2):5Google Scholar
- 29.Tagoe CE, Zezon A, Khattri S, Castellanos P (2013) Rheumatic manifestations of euthyroid, anti-thyroid antibody-positive patients. Rheumatol Int 33(7):1745–1752Google Scholar
- 30.Caturegli P, De Remigis A, Rose NR (2014) Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev 13(4–5):391–397Google Scholar
- 31.Peeters RP (2017) Subclinical hypothyroidism. N Engl J Med 377(14):1404Google Scholar
- 32.Salaffi F, Franchignoni F, Giordano A, Ciapetti A, Sarzi-Puttini P, Ottonello M (2013) Psychometric characteristics of the Italian version of the revised Fibromyalgia Impact Questionnaire using classical test theory and Rasch analysis. Clin Exp Rheumatol 31(6):41–49Google Scholar
- 33.Salaffi F, Sarzi-Puttini P, Girolimetti R, Atzeni F, Gasparini S, Grassi W (2009) Health-related quality of life in fibromyalgia patients: a comparison with rheumatoid arthritis patients and the general population using the SF-36 health survey. Clin Exp Rheumatol 27(5):67–74Google Scholar
- 34.Salaffi F, Sarzi-Puttini P, Girolimetti R, Gasparini S, Atzeni F, Grassi W (2009) Development and validation of the self-administered fibromyalgia assessment status: a disease-specific composite measure for evaluating treatment effect. Arthritis Res Ther 11(4):125Google Scholar
- 35.Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581Google Scholar
- 36.van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE et al (2013) 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis 72(11):1747–1755Google Scholar
- 37.Brito-Zeron P, Theander E, Baldini C, Seror R, Retamozo S, Quartuccio L, Bootsma H, Bowman SJ, Dörner T, Gottenberg JE et al (2016) Early diagnosis of primary Sjogren’s syndrome: EULAR-SS task force clinical recommendations. Expert Rev Clin Immunol 12(2):137–156Google Scholar
- 38.van der Heijde D, Ramiro S, Landewe R, Baraliakos X, Van den Bosch F, Sepriano A, Regel A, Ciurea A, Dagfinrud H, Dougados M et al (2017) 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 76(6):978–991Google Scholar
- 39.Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725Google Scholar
- 40.Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H, CASPAR Study Group (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54(8):2665–2673Google Scholar
- 41.Alarcón-Segovia D (1994) Mixed connective tissue disease and overlap syndromes. Clin Dermatol 12(2):309–316Google Scholar
- 42.Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Heaney RP, Murad MH, Weaver CM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1930Google Scholar
- 43.Busija L, Buchbinder R, Osborne RH (2009) Quantifying the impact of transient joint symptoms, chronic joint symptoms, and arthritis: a population-based approach. Arthritis Rheum 61:1312–1321Google Scholar
- 44.Canizares M, Badley EM (2012) Comparison of health-related outcomes for arthritis, chronic joint symptoms, and sporadic joint symptoms: a population-based study. Arthritis Care Res (Hoboken) 64:1708–1714Google Scholar
- 45.Morita S, Arima T, Matsuda M (1995) Prevalence of nonthyroid specific autoantibodies in autoimmune thyroid diseases. J Clin Endocrinol Metab 80(4):1203–1206Google Scholar
- 46.Elnady BM, Kamal NM, Shaker RH, Soliman AF, Hasan WA, Alghamdi HA, Algethami MM, Jajah MB (2016) Prevalence and clinical significance of non-organ specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases. Medicine 95:e4336Google Scholar