Skip to main content
SpringerLink
Log in

Subclinical hypothyroidism and mortality in a large Austrian cohort: a possible impact on treatment?

  • original article
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

Background

Clinical implications of subclinical hypothyroidism (SCH) are still matter of intense debate, resulting in the controversial discussion whether subclinical hypothyroidism should be treated. We performed a cohort study to evaluate the impact of subclinical hypothyroidism on vascular and overall mortality.

Methods

Between 02/1993 and 03/2004, a total of 103,135 persons attending the General Hospital Vienna with baseline serum thyrotropin (TSH, thyroid-stimulating hormone) and free thyroxin (fT4) measurements could be enrolled in a retrospective cohort study. Subclinical hypothyroidism was defined by elevated TSH ranging from 4.5 to 20.0 mIU/L and normal fT4 concentration (0.7–1.7 ng/dL). Overall and vascular mortality as primary endpoints were assessed via record linkage with the Austrian Death Registry.

Results

A total of 80,490 subjects fulfilled inclusion criteria of whom 3934 participants (3.7 %) were classified as SCH (868 males and 3066 females, median age 48 years). The mean follow-up among the 80,490 subjects was 4.1 years yielding an observation period of 373,301 person-years at risk. In a multivariate Cox regression model adjusted for age and gender TSH levels showed a dose-dependent association with all-cause mortality. The association between SCH and overall or vascular mortality was stronger in men below 60 years compared to older males or females.

Conclusion

Our data support the hypothesis that SCH might represent an independent risk factor for overall and vascular mortality, especially in men below 60 years. Whether this group would benefit from replacement therapy should be evaluated in interventional studies.

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. Helfand M. Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive services task force. Ann Intern Med. 2004;140:128–41.

    Article  PubMed  Google Scholar 

  2. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. 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. 2002;87:489–99.

    Article  CAS  PubMed  Google Scholar 

  3. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344:501–9.

    Article  CAS  PubMed  Google Scholar 

  4. Althaus BU, Staub JJ, Ryff-De Leche A, Oberhansli A, Stahelin HB. LDL/HDL-changes in subclinical hypothyroidism: possible risk factors for coronary heart disease. Clin Endocrinol (Oxf). 1988;28:157–63.

    Article  CAS  Google Scholar 

  5. Caron P, Calazel C, Parra HJ, Hoff M, Louvet JP. Decreased HDL cholesterol in subclinical hypothyroidism: the effect of l-thyroxine therapy. Clin Endocrinol (Oxf). 1990;33:519–23.

  6. Muller B, Tsakiris DA, Roth CB, Guglielmetti M, Staub JJ, Marbet GA. Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. Eur J Clin Invest. 2001;31:131–7.

  7. Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A, Soda M, et al. Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab. 2004;89:3365–70.

    Article  CAS  PubMed  Google Scholar 

  8. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam study. Ann Intern Med. 2000;132:270–8.

    Article  CAS  PubMed  Google Scholar 

  9. Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A, et al. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab. 1999;84:2064–7.

    Article  CAS  PubMed  Google Scholar 

  10. Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, Bauer DC. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med. 2005;165:2460–6.

    Article  PubMed  Google Scholar 

  11. Bengel FM, Nekolla SG, Ibrahim T, Weniger C, Ziegler SI, Schwaiger M. Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging. J Clin Endocrinol Metab. 2000;85:1822–7.

    Article  CAS  PubMed  Google Scholar 

  12. Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA. 2006;295:1033–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Walsh JP, Bremner AP, Bulsara MK, O’Leary P, Leedman PJ, Feddema P, Michelangeli V. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med. 2005;165:2467–72.

    Article  PubMed  Google Scholar 

  14. Rodondi N, Bauer DC, Cappola AR, Cornuz J, Robbins J, Fried LP, et al. Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The cardiovascular health study. J Am Coll Cardiol. 2008;52:1152–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291:228–38.

    Article  CAS  PubMed  Google Scholar 

  16. Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab. 2005;90:5483–8.

    Article  CAS  PubMed  Google Scholar 

  17. Endler G, Marsik C, Jilma B, Schickbauer T, Vormittag R, Wagner O, et al. Anti-cardiolipin antibodies and overall survival in a large cohort: preliminary report. Clin Chem. 2006;52:1040–4.

    Article  CAS  PubMed  Google Scholar 

  18. Kazemi-Shirazi L, Endler G, Winkler S, Schickbauer T, Wagner O, Marsik C. Gamma glutamyltransferase and long-term survival: Is it just the liver? Clin Chem. 2007;53:940–6.

    Article  CAS  PubMed  Google Scholar 

  19. Milionis HJ, Tambaki AP, Kanioglou CN, Elisaf MS, Tselepis AD, Tsatsoulis A. Thyroid substitution therapy induces high-density lipoprotein-associated platelet-activating factor-acetylhydrolase in patients with subclinical hypothyroidism: a potential antiatherogenic effect. Thyroid. 2005;15:455–60.

    Article  CAS  PubMed  Google Scholar 

  20. Cikim AS, Oflaz H, Ozbey N, Cikim K, Umman S, Meric M, et al. Evaluation of endothelial function in subclinical hypothyroidism and subclinical hyperthyroidism. Thyroid. 2004;14:605–9.

    Article  PubMed  Google Scholar 

  21. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, et al. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab. 2003;88:3731–7.

    Article  CAS  PubMed  Google Scholar 

  22. Razvi S, Shakoor A, Vanderpump M, Weaver JU, Pearce SH. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a metaanalysis. J Clin Endocrinol Metab. 2008;93:2998–3007.

    Article  CAS  PubMed  Google Scholar 

  23. Singh S, Duggal J, Molnar J, Maldonado F, Barsano CP, Arora R. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: a meta-analysis. Int J Cardiol. 2008;125:41–8.

    Article  PubMed  Google Scholar 

  24. Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, Rodondi N. Meta-analysis: Subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med. 2008;148:832–45.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

I want to give eminent credit to my parents and friends for their unlimited support for my research and when the sun was not shining. I also want to say thank you to the staff of the Department of Laboratory Diagnostics for their easygoing collaboration and workflow during the study period. Special thanks also to I-Fei Fang and Prof. Oswald F. Wagner for enabling the collaboration for the current project. My deep respect to all patients that made this paper possible.

Author information

Authors and Affiliations

  1. Department for Trauma Surgery, Medical University of Vienna, Vienna, Austria

    Florian Maria Kovar MD

  2. Central Laboratory, Wilhelminenspital der Stadt Wien, Vienna, Austria

    I-Fei Fang & Georg Slavka

  3. Department of Medical and Chemical Laboratory Diagnostics, Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, AKH-Wien Waehringer Guertel 18–20, 1090, Vienna, Austria

    Thomas Perkmann, Helmuth Haslacher, Manuela Födinger, Georg Endler &  Oswald F. Wagner MD

  4. Central Laboratory, Kaiser Franz Josef-Spital der Stadt Wien, Vienna, Austria

    Manuela Födinger

  5. Labors.at, Vienna, Austria

    Georg Endler

Authors
  1. Florian Maria Kovar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I-Fei Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Perkmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helmuth Haslacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Georg Slavka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manuela Födinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Georg Endler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Oswald F. Wagner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oswald F. Wagner MD.

Ethics declarations

Conflict of interests

The authors declare that there are no actual or potential conflicts of interest in relation to this article.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kovar, F., Fang, IF., Perkmann, T. et al. Subclinical hypothyroidism and mortality in a large Austrian cohort: a possible impact on treatment?. Wien Klin Wochenschr 127, 924–930 (2015). https://doi.org/10.1007/s00508-015-0846-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-015-0846-z

Keywords

Search

Navigation