Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusions
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.
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References
McLeod DS, Cooper DS (2012) The incidence and prevalence of thyroid autoimmunity. Endocrine 42(2):252–265
Ruggeri RM, Giuffrida G, Campennì A (2018) Autoimmune endocrine diseases. Minerva Endocrinol 43(3):305–322
Ajjan RA, Weetman AP (2015) The pathogenesis of Hashimoto’s thyroiditis: further developments in our understanding. Horm Metab Res 47(10):702–710
Effraimidis G, Wiersinga WM (2014) Mechanisms in endocrinology: autoimmune thyroid disease: old and new players. Eur J Endocrinol 170(6):241–252
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):599–606
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):504–511
Rosser EC, Mauri C (2016) A clinical update on the significance of the gut microbiota in systemic autoimmunity. J Autoimmun 74:85–93
de Carvalho JF, Pereira RM, Shoenfeld Y (2009) The mosaic of autoimmunity: the role of environmental factors. Front Biosci (Elite Ed) 1:501–509
Weetman AP (2011) Diseases associated with thyroid autoimmunity: explanations for the expanding spectrum. Clin Endocrinol (Oxf) 74(4):411–418
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 41:1409–1416
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 e1–9
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):240–245
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):133–141
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):523–529
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):182–186
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):575–577
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):1159–1161
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 51:291–297
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):241–246
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):484–486
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):480–486
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):809–814
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):373–380
Becker KL, Ferguson RH, McConahey WM (1963) The connective-tissue diseases and symptoms associated with Hashimoto’s thyroiditis. N Engl J Med 268:277–280
Golding DN (1993) Rheumatism and the thyroid. J R Soc Med 86(3):130–132
Chakravarty SD, Markerson JA (2013) Rheumatic manifestations of endocrine disease. Curr Opin Rheumatol 25:37–43
Punzi L, Betterle C (2004) Chronic autoimmune thyroiditis and rheumatic manifestations. Jt Bone Spine 71(4):275–283
Tagoe CE (2015) Rheumatic symptoms in autoimmune thyroiditis. Curr Rheumatol Rep 17(2):5
Tagoe CE, Zezon A, Khattri S, Castellanos P (2013) Rheumatic manifestations of euthyroid, anti-thyroid antibody-positive patients. Rheumatol Int 33(7):1745–1752
Caturegli P, De Remigis A, Rose NR (2014) Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev 13(4–5):391–397
Peeters RP (2017) Subclinical hypothyroidism. N Engl J Med 377(14):1404
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):41–49
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):67–74
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):125
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):2569–2581
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):1747–1755
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):137–156
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):978–991
Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725
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):2665–2673
Alarcón-Segovia D (1994) Mixed connective tissue disease and overlap syndromes. Clin Dermatol 12(2):309–316
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):1911–1930
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 61:1312–1321
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) 64:1708–1714
Morita S, Arima T, Matsuda M (1995) Prevalence of nonthyroid specific autoantibodies in autoimmune thyroid diseases. J Clin Endocrinol Metab 80(4):1203–1206
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:e4336
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Giuffrida, G., Bagnato, G., Campennì, A. et al. Non-specific rheumatic manifestations in patients with Hashimoto’s thyroiditis: a pilot cross-sectional study. J Endocrinol Invest 43, 87–94 (2020). https://doi.org/10.1007/s40618-019-01083-w
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DOI: https://doi.org/10.1007/s40618-019-01083-w