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Stress triggers the onset and the recurrences of hyperthyroidism in patients with Graves’ disease

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Abstract

The aim of this study was to evaluate the relationship of stressful events (SE) with the onset and outcome of Graves’ disease (GD). Over a period of 21 years, we enrolled 58 consecutive patients in whom at least one SE had occurred ≤12 months before the onset of GD. Patients were treated with antithyroid drugs (ATD) for ≥12 months and followed up for ≥5 years after ATD withdrawal. We divided patients in three groups: REM (who reached remission; 25.9 %); EXA (who experienced ≥1 exacerbation during ATD; 10.3 %); and REL (who experienced ≥1 relapse after ATD withdrawal; 63.8 %). The average age at onset was similar in the three groups. All males aged ≤25 years at GD onset relapsed at least once; no patient aged ≥51 years at GD onset relapsed ≥2 times. All patients who exacerbated or relapsed had at least one SE preceding each exacerbation or relapse. The time lag between SE and onset of GD (19.3 ± 11.9 weeks) correlated with the age at onset (r = 0.292, P = 0.0002), particularly in the REL group (r = 0.346, P = 0.001). Overall, EXA and REL patients experienced more SE than REM patients (P = 0.0002 and P = 0.003, respectively). In the REL group, the overall number of SE was correlated with the number of relapses (r = 0.486, P < 0.0001). There exist GD patients who are prone to develop hyperthyroidism and its recurrences when exposed to SE. They are relatively young; the younger these patients are, the shorter is the time lag between SE and the onset of hyperthyroidism.

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References

  1. D.S. McLeod, D.S. Cooper, The incidence and prevalence of thyroid autoimmunity. Endocrine 42, 252–265 (2012)

    Article  CAS  PubMed  Google Scholar 

  2. F. Guarneri, S. Benvenga, Environmental factors and genetic background that interact to cause autoimmune thyroid disease. Curr. Opin. Endocrinol. Diabetes Obes. 14, 398–409 (2007)

    Article  CAS  PubMed  Google Scholar 

  3. T. Mizokami, A. Wu Li, S. El-Kaissi, J.R. Wall, Stress and thyroid autoimmunity. Thyroid 14, 1047–1055 (2004)

    Article  CAS  PubMed  Google Scholar 

  4. Y. Tomer, Genetic susceptibility to autoimmune thyroid disease: past, present, and future. Thyroid 20, 715–725 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. L. Chiovato, M. Marinò, G. Perugi, E. Fiore, L. Montanelli, P. Lapi, R. Cavaliere, M. Ciampi, A. Patronelli, G. Placidi, G.F. Placidi, G.B. Cassano, A. Pinchera, Chronic recurrent stress due to panic disorder does not precipitate Graves’ disease. J. Endocrinol. Invest. 21, 758–764 (1998)

    Article  CAS  PubMed  Google Scholar 

  6. G. Effraimidis, J.G. Tijssen, J.F. Brosschot, W.M. Wiersinga, Involvement of stress in the pathogenesis of autoimmune thyroid disease: a prospective study. Psychoneuroendocrinology 37, 1191–1198 (2012)

    Article  CAS  PubMed  Google Scholar 

  7. C.H. Parry, Collected works. London 1, 478–480 (1825)

    Google Scholar 

  8. C.A. Gorman, A critical review of the role of stress in hyperthyroidism, in The thyroid gland, environment and autoimmunity, ed. by H.A. Drexhage, J.T.M. de Vijlder, W.M. Wiersinga (Elsevier Science Publishers, Amsterdam, 1990), pp. 191–200

    Google Scholar 

  9. N. Paunkovic, J. Paunkovic, O. Pavlovic, Z. Paunovic, The significant increase in incidence of Graves’ disease in eastern Serbia during the civil war in the former Yugoslavia (1992 to 1995). Thyroid 8, 37–41 (1998)

    Article  CAS  PubMed  Google Scholar 

  10. B. Winsa, A. Karlsson, R. Bergstrom, H.O. Adami, A. Gamstedt, R. Jansson, U. Adamson, P.A. Dahlberg, Stressful life events and Graves’ disease. Lancet 338, 1475–1479 (1991)

    Article  CAS  PubMed  Google Scholar 

  11. N. Sonino, M.E. Girelli, M. Boscaro, F. Fallo, B. Busnardo, G.A. Fava, Life events in the pathogenesis of Graves’ disease. A controlled study. Acta Endocrinol. (Copenh) 128, 293–296 (1993)

    CAS  Google Scholar 

  12. A.W. Kung, Life events, daily stresses and coping in patients with Graves’ disease. Clin. Endocrinol. (Oxf) 42, 303–308 (1995)

    Article  CAS  Google Scholar 

  13. V.R. Radosavljević, S.M. Janković, J.M. Marinković, Stressful life events in the pathogenesis of Graves’ disease. Eur. J. Endocrinol. 134, 699–701 (1996)

    Article  PubMed  Google Scholar 

  14. K. Yoshiuchi, H. Kumano, S. Nomura, H. Yoshimura, K. Ito, Y. Kanaji, Y. Ohashi, T. Kuboki, H. Suematsu, Stressful life events and smoking were associated with Graves’ disease in women, but not in men. Psychosom. Med. 60, 182–185 (1998)

    Article  CAS  PubMed  Google Scholar 

  15. R.C. Martin-du Pan, Triggering role of emotional stress and childbirth. Unexpected occurrence of Graves’ disease compared to 96 cases of Hashimoto thyroiditis and 97 cases of thyroid nodules. Ann. Endocrinol. (Paris) 59, 107–112 (1998)

    CAS  Google Scholar 

  16. A. Matos-Santos, E.L. Nobre, J.G.E. Costa, P.J. Nogueira, A. Macedo, A. Galvão-Teles, J.J. De Castro, Relationship between the number and impact of stressful life events and the onset of Graves’ disease and toxic nodular goitre. Clin. Endocrinol. (Oxf) 55, 15–19 (2001)

    Article  CAS  Google Scholar 

  17. M. Bagnasco, I. Bossert, G. Pesce, Stress and autoimmune thyroid diseases. NeuroImmunoModulation 13, 309–317 (2006)

    Article  CAS  PubMed  Google Scholar 

  18. C.B. Topcu, O. Celik, E. Tasan, Effect of stressful life events on the initiation of Graves’ disease. Int. J. Psychiatry Clin. Pract. 16, 307–311 (2012)

    Article  PubMed  Google Scholar 

  19. X.G. Vos, N. Smit, E. Endert, J.F. Brosschot, J.G.P. Tijssen, W.M. Wiersinga, Age and stress as determinants of the severity of hyperthyroidism caused by Graves’ disease in newly diagnosed patients. Eur. J. Endocrinol. 160, 193–199 (2009)

    Article  CAS  PubMed  Google Scholar 

  20. T.G. Strieder, M.F. Prummel, J.G. Tijssen, J.F. Brosschot, W.M. Wiersinga, Stress is not associated with thyroid peroxidase autoantibodies in euthyroid women. Brain Behav. Immun. 19, 203–206 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. G. Effraimidis, T.G. Strieder, J.G. Tijssen, W.M. Wiersinga, Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study. Eur. J. Endocrinol. 164, 107–113 (2011)

    Article  CAS  PubMed  Google Scholar 

  22. K. Yoshiuchi, H. Kumano, S. Nomura, H. Yoshimura, K. Ito, Y. Kanaji, T. Kuboki, H. Suematsu, Psychosocial factors influencing the short-term outcome of antithyroid drug therapy in Graves’ disease. Psychosom. Med. 60, 592–596 (1998)

    Article  CAS  PubMed  Google Scholar 

  23. T. Stewart, J. Rochon, R. Lenfestey, P. Wise, Correlation of stress with outcome of radioiodine therapy for Graves’ disease. J. Nucl. Med. 26, 592–599 (1985)

    CAS  PubMed  Google Scholar 

  24. S. Benvenga, Benzodiazepine and remission of Graves’ disease. Thyroid 6, 659–660 (1996)

    Article  CAS  PubMed  Google Scholar 

  25. R. Vita, D. Lapa, G. Vita, F. Trimarchi, S. Benvenga, A patient with stress-related onset and exacerbations of Graves’ disease. Nat. Clin. Pract. Endocrinol. Metab. 5, 55–61 (2009)

    Article  CAS  PubMed  Google Scholar 

  26. G. Falgarone, H.M. Heshmati, R. Cohen, G. Reach, Mechanisms in endocrinology. Role of emotional stress in the pathophysiology of Graves’ disease. Eur. J. Endocrinol. 168, R13–R18 (2012)

    Article  PubMed  Google Scholar 

  27. A. Tsatsoulis, The role of stress in the clinical expression of thyroid autoimmunity. Ann. N. Y. Acad. Sci. 1088, 382–395 (2006)

    Article  CAS  PubMed  Google Scholar 

  28. T. Nanba, M. Watanabe, N. Inoue, Y. Iwatani, Increases of the Th1/Th2 cell ratio in severe Hashimoto’s disease and in the proportion of Th17 cells in intractable Graves’ disease. Thyroid 19, 495–501 (2009)

    Article  CAS  PubMed  Google Scholar 

  29. C. Mao, S. Wang, Y. Xiao, J. Xu, Q. Jiang, M. Jin, X. Jiang, H. Guo, G. Ning, Y. Zhang, Impairment of regulatory capacity of CD4+ CD25+ regulatory T cells mediated by dendritic cell polarization and hyperthyroidism in Graves’ disease. J. Immunol. 186, 4734–4743 (2011)

    Article  CAS  PubMed  Google Scholar 

  30. A.P. Weetman, Immunity, thyroid function and pregnancy: molecular mechanisms. Nat. Rev. Endocrinol. 6, 311–318 (2010)

    Article  CAS  PubMed  Google Scholar 

  31. M. Rotondi, C. Cappelli, B. Pirali, I. Pirola, F. Magri, R. Fonte, M. Castellano, E.A. Rosei, L. Chiovato, The effect of pregnancy on subsequent relapse from Graves’ disease after a successful course of antithyroid drug therapy. J. Clin. Endocrinol. Metab. 93, 3985–3988 (2008)

    Article  CAS  PubMed  Google Scholar 

  32. J.K. Kiecolt-Glaser, K.J. Preacher, R.C. MacCallum, C. Atkinson, W.B. Malarkey, R. Glaser, Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc. Natl. Acad. Sci. USA 100, 9090–9095 (2003)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. K. Agbaht, S. Gullu, Adrenocortical reserves in hyperthyroidism. Endocrine 45, 136–143 (2014)

    Article  CAS  PubMed  Google Scholar 

  34. M.E. Forteza, Precipitating factors in hyperthyroidism. Geriatrics 28, 123–126 (1973)

    CAS  PubMed  Google Scholar 

  35. P. Vitti, T. Rago, L. Chiovato, S. Pallini, F. Santini, E. Fiore, R. Rocchi, E. Martino, A. Pinchera, Clinical features of patients with Graves’ disease undergoing remission after antithyroid drug treatment. Thyroid 7, 369–375 (1997)

    Article  CAS  PubMed  Google Scholar 

  36. A. Allahabadia, J. Daykin, R.L. Holder, M.C. Sheppard, S.C. Gough, J.A. Franklyn, Age and gender predict the outcome of treatment for Graves’ hyperthyroidism. J. Clin. Endocrinol. Metab. 85, 1038–1042 (2000)

    CAS  PubMed  Google Scholar 

  37. A. Fukao, J. Takamatsu, Y. Murakami, S. Sakane, A. Miyauchi, K. Kuma, S. Hayashi, T. Hanafusa, The relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug-treated patients with Graves’ disease. Clin. Endocrinol. (Oxf) 58, 550–555 (2003)

    Article  Google Scholar 

  38. T. Lidz, Emotional factors in the etiology of hyperthyroidism. Psychosom. Med. 11, 2–8 (1949)

    Article  CAS  PubMed  Google Scholar 

  39. E. Morillo, L.I. Gardner, Bereavement as an antecedent factor in thyrotoxicosis of childhood: four case studies with survey of possible metabolic pathways. Psychosom. Med. 41, 545–555 (1979)

    Article  CAS  PubMed  Google Scholar 

  40. S.M. Ferguson-Rayport, The relation of emotional stress factors to recurrence of thyrotoxicosis. Can. Med. Assoc. J. 75, 993–1000 (1956)

    PubMed Central  CAS  PubMed  Google Scholar 

  41. Y. Hidaka, M.N. Amino, E. Iwatani, E. Itoh, M. Matsunaga, H. Tamaki, Recurrence of thyrotoxicosis after attack of allergic rhinitis in patients with Graves’ disease. J. Clin. Endocrinol. Metab. 77, 1667–1670 (1993)

    CAS  PubMed  Google Scholar 

  42. K. Kamoi, M. Tanaka, T. Ikarashi, M. Miyakoshi, Effect of the 2004 mid Niigata prefecture earthquake on patients with endocrine disorders. Endocr. J. 53, 511–521 (2006)

    Article  CAS  PubMed  Google Scholar 

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125, Messina, Italy

    Roberto Vita, Daniela Lapa, Francesco Trimarchi & Salvatore Benvenga

  2. Master Program on Childhood, Adolescence and Women’s Endocrine Health, University of Messina, Via Consolare Valeria, 98125, Messina, Italy

    Salvatore Benvenga

  3. Interdepartmental Program of Molecular and Clinical Endocrinology and Women’s Endocrine Health, A.O.U. Policlinico G. Martino, Via Consolare Valeria, 98125, Messina, Italy

    Salvatore Benvenga

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  1. Roberto Vita
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  4. Salvatore Benvenga
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Correspondence to Roberto Vita.

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Vita, R., Lapa, D., Trimarchi, F. et al. Stress triggers the onset and the recurrences of hyperthyroidism in patients with Graves’ disease. Endocrine 48, 254–263 (2015). https://doi.org/10.1007/s12020-014-0289-8

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