Skip to main content
SpringerLink
Log in

Amiodarone-induced thyroid dysfunction in Taiwan: a retrospective cohort study

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background The incidence and risk factors of amiodarone-induced thyroid dysfunction are variable in the literature. Objective The aim of this study was to investigate the clinical and biochemical features and risk factors of amiodarone-induced thyroid dysfunction in Taiwan. Setting This study was conducted at a tertiary referral center for arrhythmia. Method Retrospective analysis of patients treated with amiodarone during the years 2008–2009 was performed. Main outcome measure Incidence and risk factors of amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH) were assessed. Results Of the 527 patients, 437 (82.9 %) remained euthyroid, 21 (4.0 %) developed AIT, and 69 (13.1 %) were affected with AIH. In univariate analysis, AIT was associated with younger age, and the risk factors for AIH included older age, higher baseline thyroid stimulating hormone (TSH) titer, lower baseline free T4 level, lower cumulative amiodarone dosage, and shorter amiodarone treatment duration. Cox regression analysis was performed to determine the different risk categories in the elderly population of age 65–74 (young-old), 75–84 (old-old), and ≥85 years old (oldest-old). Additionally increased risk of AIH was found in the groups of old-old (HR 2.09, 95 % CI 1.11–3.96) and oldest-old (HR 2.57, 95 % CI 1.21–4.75). In the multivariate analysis of risk factors for AIH, baseline TSH level (HR 1.38, 95 % CI 1.12–1.70) and cumulative amiodarone dosage (HR 0.95, 95 % CI 0.93–0.97) remained statistically significant. Conclusion AIH was much more common than AIT in Taiwan, an area with sufficient iodine intake. Higher baseline TSH level was the predominant independent risk factor for the development of AIH.

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

Similar content being viewed by others

References

  1. Vorperian VR, Havighurst TC, Miller S, January CT. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol. 1997;30:791–8.

    Article  PubMed  CAS  Google Scholar 

  2. Han TS, Williams GR, Vanderpump MP. Benzofuran derivatives and the thyroid. Clin Endocrinol. 2009;70:2–13.

    Article  CAS  Google Scholar 

  3. Cohen-Lehman J, Dahl P, Danzi S, Klein I. Effects of amiodarone therapy on thyroid function. Nat Rev Endocrinol. 2010;6:34–41.

    Article  PubMed  CAS  Google Scholar 

  4. Sidhu J, Jenkins D. Men are at increased risk of amiodarone-associated thyrotoxicosis in the UK. QJM. 2003;96:949–50.

    Article  PubMed  CAS  Google Scholar 

  5. Schaan BD, Cunha CP, Francisconi A, Zottis B, Brum G, Bruch RS, et al. Amiodarone-induced thyroid dysfunction in a tertiary center in south Brazil. Arq Bras Endocrinol Metabol. 2005;49:916–22.

    Article  PubMed  Google Scholar 

  6. Lee KF, Lee KM, Fung TT. Amiodarone-induced thyroid dysfunction in the Hong Kong Chinese population. Hong Kong Med J. 2010;16:434–9.

    PubMed  CAS  Google Scholar 

  7. Ahmed S, Van Gelder IC, Wiesfeld AC, Van Veldhuisen DJ, Links TP. Determinants and outcome of amiodarone-associated thyroid dysfunction. Clin Endocrinol. 2011;75:388–94.

    Article  CAS  Google Scholar 

  8. Stan MN, Ammash NM, Warnes CA, Brennan MD, Thapa P, Nannenga MR, et al. Body mass index and the development of amiodarone-induced thyrotoxicosis in adults with congenital heart disease-A cohort study. Int J Cardiol. 2013;167:821–6.

    Article  PubMed  Google Scholar 

  9. Zosin I, Balas M. Amiodarone-induced thyroid dysfunction in an iodine-replete area: epidemiological and clinical data. Endokrynol Pol. 2012;63:2–9.

    PubMed  Google Scholar 

  10. Martino E, Aghini-Lombardi F, Mariotti S, Bartalena L, Lenziardi M, Ceccarelli C, et al. Amiodarone iodine-induced hypothyroidism: risk factors and follow-up in 28 cases. Clin Endocrinol. 1987;26:227–37.

    Article  CAS  Google Scholar 

  11. Trip MD, Wiersinga W, Plomp TA. Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. Am J Med. 1991;91:507–11.

    Article  PubMed  CAS  Google Scholar 

  12. Aleksic Z, Aleksic A. Incidence of amiodarone-induced thyroid dysfunction and predictive factors for their occurrence. Med Pregl. 2011;64:533–8.

    Article  PubMed  Google Scholar 

  13. Martino E, Aghini-Lombardi F, Bartalena L, Grasso L, Loviselli A, Velluzzi F, et al. Enhanced susceptibility to amiodarone-induced hypothyroidism in patients with thyroid autoimmune disease. Arch Intern Med. 1994;154:2722–6.

    Article  PubMed  CAS  Google Scholar 

  14. Martino E, Safran M, Aghini-Lombardi F, Rajatanavin R, Lenziardi M, Fay M, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med. 1984;101:28–34.

    Article  PubMed  CAS  Google Scholar 

  15. Thorne SA, Barnes I, Cullinan P, Somerville J. Amiodarone-associated thyroid dysfunction: risk factors in adults with congenital heart disease. Circulation. 1999;100:149–54.

    Article  PubMed  CAS  Google Scholar 

  16. Bouvy ML, Heerdink ER, Hoes AW, Leufkens HG. Amiodarone-induced thyroid dysfunction associated with cumulative dose. Pharmacoepidemiol Drug Saf. 2002;11:601–6.

    Article  PubMed  CAS  Google Scholar 

  17. Lin HD, Lo JG, Ching KN. Amount of urinary iodine excretion in residents of Taipei City: a hospital-based study. J Chin Med Assoc. 1991;48:20–4.

    CAS  Google Scholar 

  18. Hofmann A, Nawara C, Ofluoglu S, Holzmannhofer J, Strohmer B, Pirich C. Incidence and predictability of amiodarone-induced thyrotoxicosis and hypothyroidism. Wien Klin Wochenschr. 2008;120:493–8.

    Article  PubMed  CAS  Google Scholar 

  19. Diehl LA, Romaldini JH, Graf H, Bartalena L, Martino E, Albino CC, et al. Management of amiodarone-induced thyrotoxicosis in Latin America: an electronic survey. Clin Endocrinol. 2006;65:433–8.

    Article  CAS  Google Scholar 

  20. Tanda ML, Piantanida E, Lai A, Liparulo L, Sassi L, Bogazzi F, et al. Diagnosis and management of amiodarone-induced thyrotoxicosis: similarities and differences between North American and European thyroidologists. Clin Endocrinol. 2008;69:812–8.

    Article  Google Scholar 

  21. Bartalena L, Wiersinga WM, Tanda ML, Bogazzi F, Piantanida E, Lai A, et al. Diagnosis and management of amiodarone-induced thyrotoxicosis in Europe: results of an international survey among members of the European Thyroid Association. Clin Endocrinol. 2004;61:494–502.

    Article  Google Scholar 

  22. Bogazzi F, Bartalena L, Gasperi M, Braverman LE, Martino E. The various effects of amiodarone on thyroid function. Thyroid. 2001;11:511–9.

    Article  PubMed  CAS  Google Scholar 

  23. Bongard V, Marc D, Philippe V, Jean-Louis M, Maryse LM. Incidence rate of adverse drug reactions during long-term follow-up of patients newly treated with amiodarone. Am J Ther. 2006;13:315–9.

    Article  PubMed  Google Scholar 

  24. Batcher EL, Tang XC, Singh BN, Singh SN, Reda DJ, Hershman JM, et al. Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation. Am J Med. 2007;120:880–5.

    Article  PubMed  CAS  Google Scholar 

  25. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol. 1995;43:55–68.

    Article  CAS  Google Scholar 

  26. Walsh JP, Bremner AP, Feddema P, Leedman PJ, Brown SJ, O’Leary P. Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques. J Clin Endocrinol Metab. 2010;95:1095–104.

    Article  PubMed  CAS  Google Scholar 

  27. Asvold BO, Vatten LJ, Midthjell K, Bjoro T. Serum TSH within the reference range as a predictor of future hypothyroidism and hyperthyroidism: 11-year follow-up of the HUNT Study in Norway. J Clin Endocrinol Metab. 2012;97:93–9.

    Article  PubMed  CAS  Google Scholar 

  28. Huang CC, Chen YC, Chen LK, Hwang SJ, Lin HD. Relationship between age and serum thyrotropin among asymptomatic older people in Taiwan. Arch Gerontol Geriatr. 2010;51:117–20.

    Article  PubMed  CAS  Google Scholar 

  29. Gheri RG, Pucci P, Falsetti C, Luisi ML, Cerisano GP, Gheri CF, et al. Clinical, biochemical and therapeutical aspects of amiodarone-induced hypothyroidism (AIH) in geriatric patients with cardiac arrhythmias. Arch Gerontol Geriatr. 2004;38:27–36.

    Article  PubMed  CAS  Google Scholar 

  30. Maselli M, Inelmen EM, Giantin V, Manzato E. Hypothyroidism in the elderly: diagnostic pitfalls illustrated by a case report. Arch Gerontol Geriatr. 2012;55:82–4.

    Article  PubMed  Google Scholar 

  31. Burgess C, Blaikie A, Ingham T, Robinson G, Narasimhan S. Monitoring the use of amiodarone: compliance with guidelines. Intern Med J. 2006;36:289–93.

    Article  PubMed  CAS  Google Scholar 

  32. Raebel MA, Carroll NM, Simon SR, Andrade SE, Feldstein AC, Lafata JE, et al. Liver and thyroid monitoring in ambulatory patients prescribed amiodarone in 10 HMOs. J Manag Care Pharm. 2006;12:656–64.

    PubMed  Google Scholar 

Download references

Funding

This study was partly supported by research Grants V100B-039, V101B-023, V102B-048 to L.Y.L. and V100A-013 to P.J.C from Taipei Veterans General Hospital, Taipei, Taiwan.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan

    Chun-Jui Huang, Po-Ju Chen, Tjin-Shing Jap & Liang-Yu Lin

  2. Faculty of Medicine, National Yang-Ming University, Taipei City, Taiwan

    Chun-Jui Huang, De-Feng Huang, Shih-Lin Chang, Shih-Ann Chen, Tjin-Shing Jap & Liang-Yu Lin

  3. Department of Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan

    Jing-Wen Chang

  4. Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan

    De-Feng Huang

  5. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan

    Shih-Lin Chang & Shih-Ann Chen

  6. Institute of Pharmacology, National Yang-Ming University, Taipei City, Taiwan

    Liang-Yu Lin

Authors
  1. Chun-Jui Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Po-Ju Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing-Wen Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. De-Feng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shih-Lin Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shih-Ann Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tjin-Shing Jap
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Liang-Yu Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liang-Yu Lin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, CJ., Chen, PJ., Chang, JW. et al. Amiodarone-induced thyroid dysfunction in Taiwan: a retrospective cohort study. Int J Clin Pharm 36, 405–411 (2014). https://doi.org/10.1007/s11096-013-9910-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-013-9910-9

Keywords

Search

Navigation