Thyroid function and life expectancy with and without noncommunicable diseases: A population-based study

Autoři: Arjola Bano aff001;  Layal Chaker aff001;  Francesco U. S. Mattace-Raso aff005;  Natalie Terzikhan aff002;  Maryam Kavousi aff002;  M. Arfan Ikram aff002;  Robin P. Peeters aff001;  Oscar H. Franco aff002
Působiště autorů: Department of Internal Medicine and Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, the Netherlands aff001;  Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands aff002;  Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland aff003;  Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland aff004;  Section of Geriatric Medicine, Erasmus Medical Center, Rotterdam, the Netherlands aff005
Vyšlo v časopise: Thyroid function and life expectancy with and without noncommunicable diseases: A population-based study. PLoS Med 16(10): e32767. doi:10.1371/journal.pmed.1002957
Kategorie: Research Article
doi: 10.1371/journal.pmed.1002957



Variations in thyroid function within reference ranges are associated with increased risk of diseases and death. However, the impact of thyroid function on life expectancy (LE) with and without noncommunicable diseases (NCDs) remains unknown. We therefore aimed to investigate the association of thyroid function with total LE and LE with and without NCD among euthyroid individuals.

Methods and findings

The study was embedded in the Rotterdam Study, a prospective population-based study carried out in the Netherlands. In total, 7,644 participants without known thyroid disease and with thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels within reference ranges were eligible. NCDs were defined as presence of cardiovascular disease, diabetes mellitus type 2, or cancer. We used the demographic tool of multistate life tables to calculate LE estimates at the age of 50 years, using prevalence, incidence rates, and hazard ratios for three transitions (healthy to NCD, healthy to death, and NCD to death). The total LE and LE with and without NCD among TSH and FT4 tertiles were calculated separately in men and women. Analyses were adjusted for sociodemographic and cardiovascular risk factors. The mean (standard deviation) age of the participants was 64.5 (9.7) years, and 52.3% were women. Over a median follow-up of 8 years (interquartile range 2.7–9.9 years), 1,396 incident NCD events and 1,422 deaths occurred. Compared with those in the lowest TSH tertile, men and women in the highest TSH tertile were expected to live 1.5 years (95% confidence interval [CI] 0.8–2.3, p < 0.001) and 1.5 years (CI 0.8–2.2, p < 0.001) longer, respectively, of which 1.4 years (CI 0.5–2.3, p = 0.002) and 1.3 years (CI 0.3–2.1, p = 0.004) with NCD. Compared with those in the lowest FT4 tertile, the difference in LE for men and women in the highest FT4 tertile was −3.7 years (CI −5.1 to −2.2, p < 0.001) and −3.3 years (CI −4.7 to −1.9, p < 0.001), respectively, of which −1.8 years (CI −3.1 to −0.7, p = 0.003) and −2.0 years (CI −3.4 to −0.7, p = 0.003) without NCD. A limitation of the study is the observational design. Thus, the possibility of residual confounding cannot be entirely ruled out.


In this study, we found that people with low–normal thyroid function (i.e., highest tertile of TSH and lowest tertile of FT4 reference ranges) are expected to live more years with and without NCD than those with high–normal thyroid function (i.e., lowest tertile of TSH and highest tertile of FT4 reference ranges). These findings provide support for a re-evaluation of the current reference ranges of thyroid function.

Klíčová slova:

Cardiovascular diseases – Chronic obstructive pulmonary disease – Life expectancy – Medical education – Thyroid – Thyroid-stimulating hormone – Thyroxine


1. Suhrcke M, Nugent RA, Stuckler D, Rocco L. Chronic Disease: An Economic Perspective. London: Oxford Health Alliance; 2006.

2. WHO. Global status report on noncommunicable diseases 2014. Geneva, Switzerland: WHO; 2014.

3. GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1659–724. doi: 10.1016/S0140-6736(16)31679-8 27733284

4. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2197–223. doi: 10.1016/S0140-6736(12)61689-4 23245608

5. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365–74. doi: 10.1001/jama.2010.1361 20858880

6. Collet TH, Gussekloo J, Bauer DC, den Elzen WP, Cappola AR, Balmer P, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Archives of internal medicine. 2012;172(10):799–809. doi: 10.1001/archinternmed.2012.402 22529182

7. Gencer B, Collet TH, Virgini V, Bauer DC, Gussekloo J, Cappola AR, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012;126(9):1040–9. doi: 10.1161/CIRCULATIONAHA.112.096024 22821943

8. Hellevik AI, Asvold BO, Bjoro T, Romundstad PR, Nilsen TI, Vatten LJ. Thyroid function and cancer risk: a prospective population study. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2009;18(2):570–4.

9. Gronich N, Deftereos SN, Lavi I, Persidis AS, Abernethy DR, Rennert G. Hypothyroidism is a Risk Factor for New-Onset Diabetes: A Cohort Study. Diabetes care. 2015;38(9):1657–64. doi: 10.2337/dc14-2515 26070591

10. Chiamolera MI, Wondisford FE. Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology. 2009;150(3):1091–6. doi: 10.1210/en.2008-1795 19179434

11. Chaker L, Korevaar TIM, Rizopoulos D, Collet TH, Volzke H, Hofman A, et al. Defining Optimal Health Range for Thyroid Function Based on the Risk of Cardiovascular Disease. The Journal of clinical endocrinology and metabolism. 2017;102(8):2853–61. doi: 10.1210/jc.2017-00410 28520952

12. Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. The Journal of clinical endocrinology and metabolism. 2005;90(9):5483–8. doi: 10.1210/jc.2005-0455 16148345

13. Chaker L, Ligthart S, Korevaar TI, Hofman A, Franco OH, Peeters RP, et al. Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Med. 2016;14(1):150. doi: 10.1186/s12916-016-0693-4 27686165

14. Khan SR, Chaker L, Ruiter R, Aerts JG, Hofman A, Dehghan A, et al. Thyroid Function and Cancer Risk: The Rotterdam Study. The Journal of clinical endocrinology and metabolism. 2016;101(12):5030–6. doi: 10.1210/jc.2016-2104 27648963

15. Brabant G, Beck-Peccoz P, Jarzab B, Laurberg P, Orgiazzi J, Szabolcs I, et al. Is there a need to redefine the upper normal limit of TSH? Eur J Endocrinol. 2006;154(5):633–7. doi: 10.1530/eje.1.02136 16645008

16. Chaker L, Sedaghat S, Hoorn EJ, Elzen WP, Gussekloo J, Hofman A, et al. The association of thyroid function and the risk of kidney function decline: a population-based cohort study. Eur J Endocrinol. 2016;175(6):653–60. doi: 10.1530/EJE-16-0537 27926474

17. Cappola AR, Arnold AM, Wulczyn K, Carlson M, Robbins J, Psaty BM. Thyroid function in the euthyroid range and adverse outcomes in older adults. The Journal of clinical endocrinology and metabolism. 2015;100(3):1088–96. doi: 10.1210/jc.2014-3586 25514105

18. Bano A, Chaker L, Mattace-Raso FUS, van der Lugt A, Ikram MA, Franco OH, et al. Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study. Circ Res. 2017;121(12):1392–400. doi: 10.1161/CIRCRESAHA.117.311603 29089349

19. Bano A, Chaker L, Plompen EP, Hofman A, Dehghan A, Franco OH, et al. Thyroid Function and the Risk of Nonalcoholic Fatty Liver Disease: The Rotterdam Study. The Journal of clinical endocrinology and metabolism. 2016;101(8):3204–11. doi: 10.1210/jc.2016-1300 27270473

20. Chaker L, Cappola AR, Mooijaart SP, Peeters RP. Clinical aspects of thyroid function during ageing. The lancet Diabetes & endocrinology. 2018;6(9):733–42.

21. Taylor PN, Razvi S, Pearce SH, Dayan CM. Clinical review: A review of the clinical consequences of variation in thyroid function within the reference range. The Journal of clinical endocrinology and metabolism. 2013;98(9):3562–71. doi: 10.1210/jc.2013-1315 23824418

22. Bano A, Dhana K, Chaker L, Kavousi M, Ikram MA, Mattace-Raso FUS, et al. Association of Thyroid Function With Life Expectancy With and Without Cardiovascular Disease: The Rotterdam Study. JAMA Intern Med. 2017;177(11):1650–7. doi: 10.1001/jamainternmed.2017.4836 28975207

23. Beaglehole R, Bonita R, Alleyne G, Horton R, Li L, Lincoln P, et al. UN High-Level Meeting on Non-Communicable Diseases: addressing four questions. Lancet. 2011;378(9789):449–55. doi: 10.1016/S0140-6736(11)60879-9 21665266

24. Ikram MA, Brusselle GGO, Murad SD, van Duijn CM, Franco OH, Goedegebure A, et al. The Rotterdam Study: 2018 update on objectives, design and main results. European journal of epidemiology. 2017;32(9):807–50. doi: 10.1007/s10654-017-0321-4 29064009

25. Leening MJ, Kavousi M, Heeringa J, van Rooij FJ, Verkroost-van Heemst J, Deckers JW, et al. Methods of data collection and definitions of cardiac outcomes in the Rotterdam Study. European journal of epidemiology. 2012;27(3):173–85. doi: 10.1007/s10654-012-9668-8 22388767

26. Bos MJ, Koudstaal PJ, Hofman A, Ikram MA. Modifiable etiological factors and the burden of stroke from the Rotterdam study: a population-based cohort study. PLoS Med. 2014;11(4):e1001634. doi: 10.1371/journal.pmed.1001634 24781247

27. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J. 2005;26(11):1115–40. doi: 10.1093/eurheartj/ehi204 15901669

28. Ligthart S, van Herpt TT, Leening MJ, Kavousi M, Hofman A, Stricker BH, et al. Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study. The lancet Diabetes & endocrinology. 2016;4(1):44–51.

29. De Bruijn KM, Ruiter R, de Keyser CE, Hofman A, Stricker BH, van Eijck CH. Detection bias may be the main cause of increased cancer incidence among diabetics: results from the Rotterdam Study. Eur J Cancer. 2014;50(14):2449–55. doi: 10.1016/j.ejca.2014.06.019 25047425

30. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. The New England journal of medicine. 2012;367(1):20–9. doi: 10.1056/NEJMoa1114248 22762315

31. Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function: new insights into old concepts. Clinical chemistry. 1992;38(10):1933–53. 1394976

32. Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347–65. doi: 10.1164/rccm.201204-0596PP 22878278

33. Peeters A, Mamun AA, Willekens F, Bonneux L. A cardiovascular life history. A life course analysis of the original Framingham Heart Study cohort. Eur Heart J. 2002;23(6):458–66. doi: 10.1053/euhj.2001.2838 11863348

34. Franco OH, de Laet C, Peeters A, Jonker J, Mackenbach J, Nusselder W. Effects of physical activity on life expectancy with cardiovascular disease. Archives of internal medicine. 2005;165(20):2355–60. doi: 10.1001/archinte.165.20.2355 16287764

35. Franco OH, Steyerberg EW, Hu FB, Mackenbach J, Nusselder W. Associations of diabetes mellitus with total life expectancy and life expectancy with and without cardiovascular disease. Arch Intern Med. 2007;167(11):1145–51. doi: 10.1001/archinte.167.11.1145 17563022

36. Efron B, Tibshirani RJ. An introduction to the bootstrap. New York: Chapman and Hall; 1993.

37. Yeap BB, Alfonso H, Hankey GJ, Flicker L, Golledge J, Norman PE, et al. Higher free thyroxine levels are associated with all-cause mortality in euthyroid older men: the Health In Men Study. Eur J Endocrinol. 2013;169(4):401–8. doi: 10.1530/EJE-13-0306 23853210

38. Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004;292(21):2591–9. doi: 10.1001/jama.292.21.2591 15572717

39. Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T(4) and T(3) in normal patients: a clue to the understanding of subclinical thyroid disease. The Journal of clinical endocrinology and metabolism. 2002;87(3):1068–72. doi: 10.1210/jcem.87.3.8165 11889165

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