Endocrinol Metab.  2023 Dec;38(6):729-738. 10.3803/EnM.2023.1769.

Exploring the Association between Thyroid Function and Frailty: Insights from Representative Korean Data

• Lee YJ
• Kim MH
• Lim DJ
• Lee JM
• Chang SA
• Lee J

• KMID: 2549266
• DOI: http://doi.org/10.3803/EnM.2023.1769

Abstract

Background
This study investigates the association between thyroid function and frailty in the old patients using representative data.
Methods
The study was conducted using data from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. The study population included 2,416 participants aged 50 years and older with available thyroid function test data. Frailty assessment was performed using the Fried frailty phenotype. The prevalence of frailty was analyzed across different thyroid diseases and thyroid function parameters.
Results
The significant association between thyroid dysfunction and frailty was observed in overt hyperthyroidism and subclinical hyperthyroidism. After adjusting for various factors, the association between thyroid dysfunction and frailty remained significant. On the other hand, overt hypothyroidism did not show a significant association with frailty in the adjusted analysis. For individuals with overt hyperthyroidism and subclinical hyperthyroidism, higher levels of free thyroxine (FT4) were significantly associated with an increased risk of frailty (aOR >999; 95% CI, >999 to 999). Among individuals with overt hypothyroidism, lower level of FT4 levels and high thyrotropin (TSH) levels showed a significant association with frailty risk (FT4: aOR, <0.01; TSH: aOR, 999). In participants with subclinical hypothyroidism, there were no significant associations between parameters for thyroid and frailty risk.
Conclusion
These findings suggest that thyroid dysfunction, particularly overt hyperthyroidism and subclinical hyperthyroidism, may be associated with an increased risk of frailty in the old patients.

Keyword

Frailty; Thyroid; Thyroid function tests; Aged

Reference

1. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001; 56:M146–56.

2. Hoogendijk EO, Afilalo J, Ensrud KE, Kowal P, Onder G, Fried LP. Frailty: implications for clinical practice and public health. Lancet. 2019; 394:1365–75.

3. Xue QL, Bandeen-Roche K, Tian J, Kasper JD, Fried LP. Progression of physical frailty and the risk of all-cause mortality: is there a point of no return? J Am Geriatr Soc. 2021; 69:908–15.

4. Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012; 60:1487–92.

5. Siriwardhana DD, Hardoon S, Rait G, Weerasinghe MC, Walters KR. Prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: a systematic review and meta-analysis. BMJ Open. 2018; 8:e018195.

6. Won CW, Lee S, Kim J, Chon D, Kim S, Kim CO, et al. Korean frailty and aging cohort study (KFACS): cohort profile. BMJ Open. 2020; 10:e035573.

7. Dent E, Kowal P, Hoogendijk EO. Frailty measurement in research and clinical practice: a review. Eur J Intern Med. 2016; 31:3–10.

8. Clegg A, Hassan-Smith Z. Frailty and the endocrine system. Lancet Diabetes Endocrinol. 2018; 6:743–52.

9. Kim S, Kwon YS, Kim JY, Hong KH, Park YK. Association between iodine nutrition status and thyroid disease-related hormone in Korean adults: Korean National Health and Nutrition Examination Survey VI (2013-2015). Nutrients. 2019; 11:2757.

10. Chung JH. Update on thyroid hormone levels and thyroid dysfunction in the Korean population based on data from the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). Endocrinol Metab (Seoul). 2020; 35:7–13.

11. Chun MY. Validity and reliability of Korean version of international physical activity questionnaire short form in the elderly. Korean J Fam Med. 2012; 33:144–51.

12. Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003; 35:1381–95.

13. Park SK. Frailty in Korean patients with chronic obstructive pulmonary disease, using data from the Korea National Health and Nutrition Examination Survey, 2015 and 2016. Appl Nurs Res. 2021; 59:151417.

14. Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al. Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc. 2014; 15:95–101.

15. To TL, Doan TN, Ho WC, Liao WC. Prevalence of frailty among community-dwelling older adults in Asian countries: a systematic review and meta-analysis. Healthcare (Basel). 2022; 10:895.

16. O’Caoimh R, Sezgin D, O’Donovan MR, Molloy DW, Clegg A, Rockwood K, et al. Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies. Age Ageing. 2021; 50:96–104.

17. Buta BJ, Walston JD, Godino JG, Park M, Kalyani RR, Xue QL, et al. Frailty assessment instruments: systematic characterization of the uses and contexts of highly-cited instruments. Ageing Res Rev. 2016; 26:53–61.

18. van den Beld AW, Kaufman JM, Zillikens MC, Lamberts SW, Egan JM, van der Lely AJ. The physiology of endocrine systems with ageing. Lancet Diabetes Endocrinol. 2018; 6:647–58.

19. Cappola AR, Desai AS, Medici M, Cooper LS, Egan D, Sopko G, et al. Thyroid and cardiovascular disease: research agenda for enhancing knowledge, prevention, and treatment. Circulation. 2019; 139:2892–909.

20. Brennan MD, Powell C, Kaufman KR, Sun PC, Bahn RS, Nair KS. The impact of overt and subclinical hyperthyroidism on skeletal muscle. Thyroid. 2006; 16:375–80.

21. De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016; 388:906–18.

22. Delitala AP, Scuteri A, Doria C. Thyroid hormone diseases and osteoporosis. J Clin Med. 2020; 9:1034.

23. Bhalla NS, Vinales KL, Li M, Bhattarai R, Fawcett J, Harman SM. Low TSH is associated with frailty in an older veteran population independent of other thyroid function tests. Gerontol Geriatr Med. 2021; 7:2333721420986028.

24. Virgini VS, Rodondi N, Cawthon PM, Harrison SL, Hoffman AR, Orwoll ES, et al. Subclinical thyroid dysfunction and frailty among older men. J Clin Endocrinol Metab. 2015; 100:4524–32.

25. Guan B, Luo J, Huang X, Tian F, Sun S, Ma Y, et al. Association between thyroid hormone levels and frailty in the community-dwelling oldest-old: a cross-sectional study. Chin Med J (Engl). 2022; 135:1962–8.

26. Gaitonde DY, Rowley KD, Sweeney LB. Hypothyroidism: an update. Am Fam Physician. 2012; 86:244–51.

27. Segna D, Bauer DC, Feller M, Schneider C, Fink HA, Aubert CE, et al. Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. J Intern Med. 2018; 283:56–72.

28. Ye Y, Wang Y, Li S, Guo J, Ding L, Liu M. Association of hypothyroidism and the risk of cognitive dysfunction: a meta-analysis. J Clin Med. 2022; 11:6726.

29. Ruggeri RM, Trimarchi F, Biondi B. Management of endocrine disease: l-thyroxine replacement therapy in the frail elderly: a challenge in clinical practice. Eur J Endocrinol. 2017; 177:R199–217.

30. Veronese N, Fernando-Watutantrige S, Maggi S, Noale M, Stubbs B, Incalzi RA, et al. Serum thyroid-stimulating hormone levels and frailty in the elderly: the Progetto Veneto Anziani Study. Rejuvenation Res. 2017; 20:165–72.

31. Caraccio N, Natali A, Sironi A, Baldi S, Frascerra S, Dardano A, et al. Muscle metabolism and exercise tolerance in subclinical hypothyroidism: a controlled trial of levothyroxine. J Clin Endocrinol Metab. 2005; 90:4057–62.

32. Lankhaar JA, de Vries WR, Jansen JA, Zelissen PM, Backx FJ. Impact of overt and subclinical hypothyroidism on exercise tolerance: a systematic review. Res Q Exerc Sport. 2014; 85:365–89.

33. Biondi B, Wartofsky L. Treatment with thyroid hormone. Endocr Rev. 2014; 35:433–512.

34. Simonides WS, van Hardeveld C. Thyroid hormone as a determinant of metabolic and contractile phenotype of skeletal muscle. Thyroid. 2008; 18:205–16.

35. Bano A, Chaker L, Mattace-Raso FU, 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; 121:1392–400.

36. Stuijver DJ, van Zaane B, Romualdi E, Brandjes DP, Gerdes VE, Squizzato A. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis. Thromb Haemost. 2012; 108:1077–88.

37. Chaker L, Wolters FJ, Bos D, Korevaar TI, Hofman A, van der Lugt A, et al. Thyroid function and the risk of dementia: the Rotterdam Study. Neurology. 2016; 87:1688–95.

38. Murphy E, Gluer CC, Reid DM, Felsenberg D, Roux C, Eastell R, et al. Thyroid function within the upper normal range is associated with reduced bone mineral density and an increased risk of nonvertebral fractures in healthy euthyroid postmenopausal women. J Clin Endocrinol Metab. 2010; 95:3173–81.

39. Bano A, Chaker L, Schoufour J, Ikram MA, Kavousi M, Franco OH, et al. High circulating free thyroxine levels may increase the risk of frailty: the Rotterdam Study. J Clin Endocrinol Metab. 2018; 103:328–35.

40. Wang GC, Talor MV, Rose NR, Cappola AR, Chiou RB, Weiss C, et al. Thyroid autoantibodies are associated with a reduced prevalence of frailty in community-dwelling older women. J Clin Endocrinol Metab. 2010; 95:1161–8.