Skip to main content

Advertisement

SpringerLink
Log in

The association between Takotsubo cardiomyopathy and thyrotoxicosis: A systematic review

  • Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

This study aims to review all published cases on the association between thyrotoxicosis and Takutsubo Syndrome by describing clinical characteristics, diagnostic work-up, treatment, and outcome.

Methods

We searched PubMed and Embase databases from inception to the 17th of February 2022 for case reports or series reporting the above-mentioned association. We extracted data on demographic characteristics, clinical features, diagnostic work-up, treatment, and clinical outcomes. Cases were stratified into groups based on the presumed cause of the thyrotoxicosis (iatrogenic vs non-iatrogenic and Graves’ diseases vs non-Graves’ disease, respectively).

Results

We identified 25 cases from 24 articles. The mean age was 61.7 years (+/− SD 14.5). Most patients were women (88%). Graves’ disease (52%) was the leading cause of thyrotoxicosis. Previous cancer was significantly more common in patients with iatrogenic thyrotoxicosis (P = 0.03). The most common symptoms were respiratory symptoms (68%), chest pain (56%), and palpitations (40%). The most common ECG characteristics were T-wave abnormalities (48%) and ST-elevations (36%). Elevated troponin levels were found in 92% of the cases. Patients with Graves’s disease and Takutsubo Syndrome had higher plasma levels of serum thyroxine (P = 0.03) and were more often treated with beta-blockers (P = 0.01) compared to patients with thyrotoxicosis of other origins. Notably, 40% of cases experienced in-hospital complications. No deaths were reported. All patients had improved cardiac function within a median follow-up of 42 days.

Conclusion

Evidence-based on current case reports suggests an increased risk of Takutsubo Syndrome and subsequently increased risk of in-hospital complications in patients with thyrotoxicosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. H. Sato, H. Taiteishi, T. Uchida, Takotsubo-type cardiomyopathy due to multivessel spasm. Clinical aspect of myocardial injury: from ischemia to heart failure: From Ischemia to Heart Failure, Kagakuhyouronsya, Tokyo, 56–64 (1990)

  2. K. Dote, H. Sato, H. Tateishi, T. Uchida, et al. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases. J. Cardiol. 21, 203–214 (1991)

    CAS  PubMed  Google Scholar 

  3. J.-R. Ghadri, I.S. Wittstein, A. Prasad, S. Sharkey, et al. International expert consensus document on Takotsubo Syndrome (Part I): Clinical characteristics, diagnostic criteria, and pathophysiology. Eur. Heart J. 39, 2032–2046 (2018). https://doi.org/10.1093/eurheartj/ehy076

    Article  PubMed  PubMed Central  Google Scholar 

  4. D.C. Scantlebury, A. Prasad, Diagnosis of Takotsubo Cardiomyopathy:—Mayo Clinic Criteria. Circ. J. 78, 2129–2139 (2014). https://doi.org/10.1253/circj.CJ-14-0859

    Article  PubMed  Google Scholar 

  5. A. Garmendia Madariaga, S. Santos Palacios, F. Guillén-Grima, J.C. Galofré, The incidence and prevalence of thyroid dysfunction in Europe: A meta-analysis. J. Clin. Endocrinol. Metab. 99, 923–931 (2014). https://doi.org/10.1210/jc.2013-2409

    Article  CAS  PubMed  Google Scholar 

  6. J.G. Hollowell, N.W. Staehling, W.D. Flanders, W.H. Hannon, et al. 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. 87, 489–499 (2002). https://doi.org/10.1210/jcem.87.2.8182

    Article  CAS  PubMed  Google Scholar 

  7. S.W. Bahouth, Thyroid hormones transcriptionally regulate the beta 1-adrenergic receptor gene in cultured ventricular myocytes. J. Biol. Chem. 266, 15863–15869 (1991). https://doi.org/10.1016/S0021-9258(18)98488-7

    Article  CAS  PubMed  Google Scholar 

  8. S.W. Bahouth, X. Cui, M.J. Beauchamp, E.A. Park, Thyroid hormone Inducesβ1-adrenergic receptor gene transcription through a direct repeat separated by five nucleotides. J. Mol. Cell. Cardiol. 29, 3223–3237 (1997). https://doi.org/10.1006/jmcc.1997.0549

    Article  CAS  PubMed  Google Scholar 

  9. S. Gupta, P. Goyal, S. Idrees, S. Aggarwal, et al. Association of endocrine conditions with takotsubo cardiomyopathy: a comprehensive review. J. Am. Heart Assoc. 7, e009003 (2018). https://doi.org/10.1161/JAHA.118.009003

    Article  PubMed  PubMed Central  Google Scholar 

  10. M.J. Page, J.E. McKenzie, P.M. Bossuyt, I. Boutron, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. n71 (2021). https://doi.org/10.1136/bmj.n71

  11. Z. Munn, T.H. Barker, S. Moola, C. Tufanaru, et al. Methodological quality of case series studies: an introduction to the JBI critical appraisal tool. JBI Evid. Synth. 18, 2127–2133 (2020). https://doi.org/10.11124/JBISRIR-D-19-00099

    Article  PubMed  Google Scholar 

  12. A.S.M. Zuhdi, Z.H. Yaakob, M.A. Sadiq, M.D. Ismail, A.W. Undok, W.A.W. Ahmad, Takotsubo cardiomyopathy in association with hyperthyroidism. Medicine 47, 219–221 (2011)

    Google Scholar 

  13. N.W.C.J. van de Donk, Y.G.C.J. America, P.M.J. Zelissen, B.J.B. Hamer, Takotsubo cardiomyopathy following radioiodine therapy for toxic multinodular goitre. Neth. J. Med. 67, 350–352 (2009)

    PubMed  Google Scholar 

  14. M. Ugurlucan, Y. Zorman, G. Ates, A. Arslan, Y. Yildiz, A. Zor, S. Cicek, Takotsubo cardiomyopathy in a patient with multiple autoimmune disorders and hyperthyroidism. Res. Cardiovasc. Med. 2, 145 (2013). https://doi.org/10.5812/cardiovascmed.10023

    Article  PubMed  PubMed Central  Google Scholar 

  15. A.M. Saleh, S. Kramer, C. Kleinecke, M. Duecker, et al. Tako-tsubo cardiomyopathy during a thyroid storm; a critical intersection. Clinical cases from the ESC Cardiologists of Tomorrow, 1218 (2015)

  16. T. Sakaki, Y. Fujioka, T. Akagami, M. Masai, et al. Cardiac wall motion abnormalities observed in a patient with transient hyperthyroidism. Jpn Heart J. 45, 1071–1077 (2004). https://doi.org/10.1536/jhj.45.1071

    Article  PubMed  Google Scholar 

  17. D. Rueda, R. Aguirre, D. Contardo, P. Finocchietto, et al. Takotsubo myocardiopathy and hyperthyroidism: a case report and literature review. Am. J. Case Rep. 18, 865–870 (2017). https://doi.org/10.12659/AJCR.905121

    Article  PubMed  PubMed Central  Google Scholar 

  18. A.M. Rossor, S.H.S. Pearce, P.C. Adams, Left ventricular apical ballooning (Takotsubo Cardiomyopathy) in Thyrotoxicosis. Thyroid 17, 181–182 (2007). https://doi.org/10.1089/thy.2006.0102

    Article  PubMed  Google Scholar 

  19. A. Radhakrishnan, J.E. Granato, An association between Takotsubo cardiomyopathy and thyroid storm. Postgrad. Med. 121, 126–130 (2009). https://doi.org/10.3810/pgm.2009.05.2012

    Article  PubMed  Google Scholar 

  20. M.J. Perkins, D.T. Schachter, Biventricular Takotsubo cardiomyopathy in Graves hyperthyroidism. J. Invasive Cardiol. 26, E35–E36 (2014)

    PubMed  Google Scholar 

  21. K. Patel, G.T. Griffing, P.J. Hauptman, J.M. Stolker, Recurrent Takotsubo cardiomyopathy related to recurrent thyrotoxicosis. Tex. Heart Inst. J. 43, 152–155 (2016). https://doi.org/10.14503/THIJ-15-5046

    Article  PubMed  PubMed Central  Google Scholar 

  22. S. Omar, E. Ali, H. Mazek, T. Mahmood, et al. Takotsubo Cardiomyopathy associated with hyperthyroidism treated with thyroidectomy. Bayl. Univ. Med. Cent. Proc. 28, 194–195 (2015). https://doi.org/10.1080/08998280.2015.11929227

    Article  Google Scholar 

  23. D. Murdoch, W. O’Callaghan, E. Reda, S. Niranjan, Takotsubo Cardiomyopathy associated with primary hyperthyroidism secondary to toxic multinodular goiter. Int J. Angiol. 25, e121–e122 (2015). https://doi.org/10.1055/s-0035-1548548

    Article  PubMed  PubMed Central  Google Scholar 

  24. S. Miyazaki, T. Kamiishi, N. Hosokawa, M. Komura, et al. Reversible left ventricular dysfunction “takotsubo” cardiomyopathy associated with hyperthyroidism. Jpn Heart J. 45, 889–894 (2004). https://doi.org/10.1536/jhj.45.889

    Article  PubMed  Google Scholar 

  25. C.S. Martin, L.N. Ionescu, C.G. Barbu, A.E. Sirbu, et al. Takotsubo cardiomyopathy and transient thyrotoxicosis during combination therapy with interferon-alpha and ribavirin for chronic hepatitis C. BMC Endocr. Disord. 14, 10 (2014). https://doi.org/10.1186/1472-6823-14-10

    Article  PubMed  PubMed Central  Google Scholar 

  26. S.-A. Kwon, J.H. Yang, M.-K. Kim, S.W. Park, et al. A case of Takotsubo cardiomyopathy in a patient with Iatrogenic thyrotoxicosis. Int. J. Cardiol. 145, e111–e113 (2010). https://doi.org/10.1016/j.ijcard.2009.06.040

    Article  PubMed  Google Scholar 

  27. O. Kuboyama, T. Tokunaga, K. Kobayashi, T. Iwai, et al. A case of asymptomatic patient with hyperthyroidism documented the onset of Takotsubo cardiomyopathy by holter monitoring. Int. J. Cardiol. 151, e82–e84 (2011). https://doi.org/10.1016/j.ijcard.2010.05.055

    Article  PubMed  Google Scholar 

  28. D.C. Hutchings, D. Adlam, V. Ferreira, T.D. Karamitsos, et al. Takotsubo cardiomyopathy in association with endogenous and exogenous thyrotoxicosis. QJM 104, 433–435 (2011). https://doi.org/10.1093/qjmed/hcq099

    Article  CAS  PubMed  Google Scholar 

  29. J.S. Gundara, J.C. Lee, J. Ip, S.B. Sidhu, Takotsubo cardiomyopathy complicating thyroidectomy for graves’ disease. Thyroid 22, 975–976 (2012). https://doi.org/10.1089/thy.2012.0101

    Article  PubMed  Google Scholar 

  30. M. Eliades, D. El-Maouche, C. Choudhary, B. Zinsmeister, et al. Takotsubo cardiomyopathy associated with thyrotoxicosis: a case report and review of the literature. Thyroid 24, 383–389 (2014). https://doi.org/10.1089/thy.2012.0384

    Article  PubMed  PubMed Central  Google Scholar 

  31. A. Dimakopoulou, K. Vithian, D. Gannon, A. Harkness, Stress cardiomyopathy (Takotsubo) following radioactive iodine therapy. Endocrinology, Diabetes & Metabolism Case Reports. 2015, (2015). https://doi.org/10.1530/EDM-15-0053

  32. E. Cervilla-Muñoz, M. Bringas-Beranek, P. Demelo-Rodríguez, Iatrogenic hyperthyroidism can be a triggering factor for takotsubo cardiomyopathy. Med. Clínica 155, 42–43 (2020). https://doi.org/10.1016/j.medcli.2019.02.014

    Article  Google Scholar 

  33. I. Capel, E. Tasa-Vinyals, A. Cano-Palomares, I. Bergés-Raso, et al. Takotsubo cardiomyopathy in amiodarone-induced hyperthyroidism. Endocrinology, Diabetes & Metabolism Case Reports. 2017, (2017). https://doi.org/10.1530/EDM-16-0116

  34. E. Bird-Lake, Severe transient left ventricular dysfunction induced by thyrotoxicosis. Neth. Heart J. 19, 352–354 (2011). https://doi.org/10.1007/s12471-011-0113-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. F. Alidjan, M. Ezzhati, W. Bruggeling, C. van Guldener, Takotsubo cardiomyopathy precipitated by thyrotoxicosis. Thyroid 20, 1427–1428 (2010). https://doi.org/10.1089/thy.2009.0444

    Article  PubMed  Google Scholar 

  36. A. Al-Salameh, J. Allain, P. Meimoun, T. Benali, et al. Takotsubo cardiomyopathy can occur in patients with apathetic hyperthyroidism. Thyroid 24, 400–401 (2014). https://doi.org/10.1089/thy.2013.0354

    Article  PubMed  Google Scholar 

  37. S. Aggarwal, R. Papani, V. Gupta, Can thyroid break your heart? Role of thyroid in Takotsubo cardiomyopathy: A single center retrospective study. Int. J. Cardiol. 184, 545–546 (2015). https://doi.org/10.1016/j.ijcard.2015.02.058

    Article  PubMed  Google Scholar 

  38. A. Aweimer, I. El‐Battrawy, I. Akin, M. Borggrefe, et al. Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study. J. Intern. Med. 289, 675–687 (2021). https://doi.org/10.1111/joim.13189

    Article  CAS  PubMed  Google Scholar 

  39. Y.J. Akashi, K. Nakazawa, M. Sakakibara, F. Miyake, et al. 123I-MIBG myocardial scintigraphy in patients with “takotsubo” cardiomyopathy. J. Nucl. Med. 45, 1121–1127 (2004)

    PubMed  Google Scholar 

  40. G.S. Levey, I. Klein, Catecholamine-thyroid hormone interactions and the cardiovascular manifestations of hyperthyroidism. Am. J. Med. 88, 642–646 (1990). https://doi.org/10.1016/0002-9343(90)90533-J

    Article  CAS  PubMed  Google Scholar 

  41. R. Vassy, Y.L. Yin, G.Y. Perret, Acute effect of T3 on beta-Adrenoceptors of Cultured Chick Cardiac Myocyte. In: Braverman LE, Eber O, Langsteger W, eds. Heart and Thyroid. Wien: Blackwell-MZV, 165–168 (1994)

  42. B.D. Hoit, S.F. Khoury, Y. Shao, M. Gabel, et al. Effects of thyroid hormone on cardiac β-adrenergic responsiveness in conscious baboons. Circulation 96, 592–598 (1997). https://doi.org/10.1161/01.CIR.96.2.592

    Article  CAS  PubMed  Google Scholar 

  43. H. Mori, S. Ishikawa, S. Kojima, J. Hayashi, et al. Increased responsiveness of left ventricular apical myocardium to adrenergic stimuli. Cardiovasc. Res. 27, 192–198 (1993). https://doi.org/10.1093/cvr/27.2.192

    Article  CAS  PubMed  Google Scholar 

  44. A.R. Lyon, P.S. Rees, S. Prasad, P.A. Poole-Wilson, S.E. Harding, Stress (Takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat. Rev. Cardiol. 5, 22–29 (2008). https://doi.org/10.1038/ncpcardio1066

    Article  CAS  Google Scholar 

  45. E.S. Bachman, T.G. Hampton, H. Dhillon, I. Amende, et al. The metabolic and cardiovascular effects of hyperthyroidism are largely independent of β-adrenergic stimulation. Endocrinology 145, 2767–2774 (2004). https://doi.org/10.1210/en.2003-1670

    Article  CAS  PubMed  Google Scholar 

  46. M. Cakir, Takotsubo cardiomyopathy in thyrotoxicosis. Int. J. Cardiol. 145, 499–500 (2010). https://doi.org/10.1016/j.ijcard.2009.10.041

    Article  PubMed  Google Scholar 

  47. J. Brenes-Salazar, Takotsubo cardiomyopathy associated with severe hypothyroidism in an elderly female. Heart Views 17, 72 (2016). https://doi.org/10.4103/1995-705X.185119

    Article  PubMed  PubMed Central  Google Scholar 

  48. T. Micallef, M. Gruppetta, A. Cassar, S. Fava, Takotsubo cardiomyopathy and severe hypothyroidism. J. Cardiovasc. Med. 12, 824–827 (2011). https://doi.org/10.2459/JCM.0b013e3283403454

    Article  Google Scholar 

  49. J.-R. Ghadri, I.S. Wittstein, A. Prasad, S. Sharkey, et al. International expert consensus document on Takotsubo Syndrome (Part II): diagnostic workup, outcome, and management. Eur. Heart J. 39, 2047–2062 (2018). https://doi.org/10.1093/eurheartj/ehy077

    Article  PubMed  PubMed Central  Google Scholar 

  50. D.S. Ross, H.B. Burch, D.S. Cooper, M.C. Greenlee, et al. 2016 American Thyroid Association Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26, 1343–1421 (2016). https://doi.org/10.1089/thy.2016.0229

    Article  PubMed  Google Scholar 

  51. G.J. Kahaly, L. Bartalena, L. Hegedüs, L. Leenhardt, K. Poppe, S.H. Pearce, 2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism. Eur. Thyroid J. 7, 167–186 (2018). https://doi.org/10.1159/000490384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. T.A. McDonagh, M. Metra, M. Adamo, R.S. Gardner, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. ehab368 (2021). https://doi.org/10.1093/eurheartj/ehab368

  53. C. Templin, J.R. Ghadri, J. Diekmann, L.C. Napp, et al. Clinical features and outcomes of Takotsubo (Stress) Cardiomyopathy. N. Engl. J. Med. 373, 929–938 (2015). https://doi.org/10.1056/NEJMoa1406761

    Article  CAS  PubMed  Google Scholar 

Download references

Author contributions

A.M.: conceptualization(lead), methodology (lead), investigation (lead), formal analysis (lead), writing-original draft (lead), writing-review and editing (equal), final approval of manuscript (equal), project administration (lead). T.B.: conceptualization(lead), methodology (lead), investigation (lead), formal analysis (lead), writing-original draft (lead), writing-review and editing (equal), final approval of manuscript (equal), project administration (lead). M.O.: writing-review and editing (equal), final approval of manuscript (equal). N.A.: writing-review and editing (equal), final approval of manuscript (equal). S.B.: conceptualization (supporting), writing-review and editing (equal), final approval of manuscript (equal), supervision (lead).

Funding

A.M.: no funding to declare. T.B.: no funding to declare. M.O.: no funding to declare. N.A.: no funding to declare. S.J.B.: received grant from Desirée and Niels Ydes Foundation.

Author information

Author notes

  1. These authors contributed equally: Abdullahi Ahmed Mohamed, Tayfun Basaran.

Authors and Affiliations

  1. Department of Cardiology, Region Hospital West Jutland, Herning, Denmark

    Abdullahi Ahmed Mohamed

  2. Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen, Denmark

    Tayfun Basaran

  3. Department of Neurology, Rigshospitalet, Copenhagen, Denmark

    Marwan Hassan Othman

  4. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark

    Niels Holmark Andersen

  5. Department of Endocrinology, Odense University Hospital, Odense, Denmark

    Steen Joop Bonnema

Authors
  1. Abdullahi Ahmed Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tayfun Basaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marwan Hassan Othman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Niels Holmark Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Steen Joop Bonnema
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abdullahi Ahmed Mohamed.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohamed, A.A., Basaran, T., Othman, M.H. et al. The association between Takotsubo cardiomyopathy and thyrotoxicosis: A systematic review. Endocrine 78, 418–428 (2022). https://doi.org/10.1007/s12020-022-03174-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-022-03174-w

Keywords

Search

Navigation