Cardiovascular Outcomes of Differentiated Thyroid Cancer Patients on Long Term TSH Suppression: A Systematic Review and Meta-Analysis

Abstract

We performed a systematic review and meta-analysis of the literature regarding cardiovascular outcomes of differentiated thyroid cancer (DTC) patients who are on long term thyroid stimulating hormone suppression. Searches were carried out using Prisma guidelines in Medline, Embase, CENTRAL, CINAHL and Scopus databases. Eligible papers were those which investigated discrete cardiovascular clinical outcomes in TSH suppressed patients and meta-analysis of selected studies was performed using Revman 5.4.1. We found a total of 195 879 DTC patients with median length to follow up of 8.6 years (range 5–18.8 years). Analysis showed DTC patients to be at higher risk of atrial fibrillation (HR 1.58, 95% CI 1.40, 1.77), stroke (HR 1.14, 95% CI 1.09, 1.20) and all-cause mortality (HR 2.04, 95% CI 1.02, 4.07). However, there was no difference in risk of heart failure, ischemic heart disease or cardiovascular mortality. These findings suggest that degree of TSH suppression must be titrated to accommodate risk of cancer recurrence and cardiovascular morbidity.

Key words

TSH suppression - cardiovascular disease - thyroid malignancy - heart disease - thyroid cancer

Publikationsverlauf

Eingereicht: 25. Oktober 2022

Angenommen nach Revision: 21. April 2023

Artikel online veröffentlicht:
09. Juni 2023

• References

• 1 Rossi ED, Pantanowitz L, Hornick JL. A worldwide journey of thyroid cancer incidence centred on tumour histology. Lancet Diabetes Endocrinol 2021; 9: 193-194
• 2 Morris LG, Sikora AG, Tosteson TD. et al. The increasing incidence of thyroid cancer: the influence of access to care. Thyroid 2013; 23: 885-891
• 3 Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet 2016; 388: 2783-2795
• 4 Ganly I, Nixon IJ, Wang LY. et al. Survival from differentiated thyroid cancer: what has age got to do with it?. Thyroid 2015; 25: 1106-1114
• 5 Lundgren CI, Hall P, Ekbom A. et al. Incidence and survival of Swedish patients with differentiated thyroid cancer. Int J Cancer 2003; 106: 569-573
• 6 Brabant G. Thyrotropin suppressive therapy in thyroid carcinoma: what are the targets?. J Clin Endocrinol Metab 2008; 93: 1167-1169
• 7 Pacini F, Schlumberger M, Dralle H. et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006; 154: 787-803
• 8 Santos Palacios S, Pascual-Corrales E, Galofre JC. Management of subclinical hyperthyroidism. Int J Endocrinol Metab 2012; 10: 490-496
• 9 Biondi B, Palmieri EA, Klain M. et al. Subclinical hyperthyroidism: clinical features and treatment options. Eur J Endocrinol 2005; 152: 1-9
• 10 Collet TH, Gussekloo J, Bauer DC. et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012; 172: 799-809
• 11 Biondi B, Kahaly GJ. Cardiovascular involvement in patients with different causes of hyperthyroidism. Nat Rev Endocrinol 2010; 6: 431-443
• 12 Biondi B, Palmieri EA, Lombardi G. et al. Effects of thyroid hormone on cardiac function: the relative importance of heart rate, loading conditions, and myocardial contractility in the regulation of cardiac performance in human hyperthyroidism. J Clin Endocrinol Metab 2002; 87: 968-974
• 13 Smit JW, Eustatia-Rutten CF, Corssmit EP. et al. Reversible diastolic dysfunction after long-term exogenous subclinical hyperthyroidism: a randomized, placebo-controlled study. J Clin Endocrinol Metab 2005; 90: 6041-6047
• 14 Shargorodsky M, Serov S, Gavish D. et al. Long-term thyrotropin-suppressive therapy with levothyroxine impairs small and large artery elasticity and increases left ventricular mass in patients with thyroid carcinoma. Thyroid 2006; 16: 381-386
• 15 Horne MK, Singh KK, Rosenfeld KG. et al. Is thyroid hormone suppression therapy prothrombotic?. J Clin Endocrinol Metab 2004; 89: 4469-4473
• 16 American Thyroid Association Guidelines Taskforce on Thyroid N, Differentiated. Thyroid C, Cooper DS. et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19: 1167-1214
• 17 Do Cao C, Wemeau JL. Risk-benefit ratio for TSH- suppressive levothyroxine therapy in differentiated thyroid cancer. Ann Endocrinol (Paris) 2015; 76: 1S47-52S47
• 18 Klein Hesselink EN, Klein Hesselink MS, de Bock GH. et al. Long-term cardiovascular mortality in patients with differentiated thyroid carcinoma: an observational study. J Clin Oncol 2013; 31: 4046-4053
• 19 Klein Hesselink EN, Lefrandt JD, Schuurmans EP. et al. Increased risk of atrial fibrillation after treatment for differentiated thyroid carcinoma. J Clin Endocrinol Metab 2015; 100: 4563-4569
• 20 Klein Hesselink MS, Bocca G, Hummel YM. et al. Diastolic dysfunction is common in survivors of pediatric differentiated thyroid carcinoma. Thyroid 2017; 27: 1481-1489
• 21 Pajamaki N, Metso S, Hakala T. et al. Long-term cardiovascular morbidity and mortality in patients treated for differentiated thyroid cancer. Clin Endocrinol (Oxf) 2018; 88: 303-310
• 22 Toulis KA, Viola D, Gkoutos G. et al. Risk of incident circulatory disease in patients treated for differentiated thyroid carcinoma with no history of cardiovascular disease. Clin Endocrinol (Oxf) 2019; 91: 323-330
• 23 Zoltek M, Andersson TM, Hedman C. et al. Cardiovascular incidence in 6900 patients with differentiated thyroid cancer: a Swedish nationwide study. World J Surg 2020; 44: 436-441
• 24 Abonowara A, Quraishi A, Sapp JL. et al. Prevalence of atrial fibrillation in patients taking TSH suppression therapy for management of thyroid cancer. Clin Invest Med 2012; 35: E152-E156
• 25 Park J, Blackburn BE, Ganz PA. et al. Risk Factors for cardiovascular disease among thyroid cancer survivors: findings from the Utah cancer survivors study. J Clin Endocrinol Metab 2018; 103: 2468-2477
• 26 Wang LY, Smith AW, Palmer FL. et al. Thyrotropin suppression increases the risk of osteoporosis without decreasing recurrence in ATA low- and intermediate-risk patients with differentiated thyroid carcinoma. Thyroid 2015; 25: 300-307
• 27 Suh B, Shin DW, Park Y. et al. Increased cardiovascular risk in thyroid cancer patients taking levothyroxine: a nationwide cohort study in Korea. Eur J Endocrinol 2019; 180: 11-20
• 28 Bielecka-Dabrowa A, Mikhailidis DP, Rysz J. et al. The mechanisms of atrial fibrillation in hyperthyroidism. Thyroid Res 2009; 2: 4
• 29 Squizzato A, Gerdes VE, Brandjes DP. et al. Thyroid diseases and cerebrovascular disease. Stroke 2005; 36: 2302-2310
• 30 Sheu JJ, Kang JH, Lin HC. et al. Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study. Stroke 2010; 41: 961-966
• 31 Brito JP, Hay ID, Morris JC. Low risk papillary thyroid cancer. BMJ 2014; 348: g3045
• 32 Eustatia-Rutten CF, Corssmit EP, Biermasz NR. et al. Survival and death causes in differentiated thyroid carcinoma. J Clin Endocrinol Metab 2006; 91: 313-319
• 33 Flynn RW, Bonellie SR, Jung RT. et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 2010; 95: 186-193
• 34 Sundaram V, Hanna AN, Koneru L. et al. Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation. J Clin Endocrinol Metab 1997; 82: 3421-3424
• 35 Wang R, Yang L, Jin S. et al. Thyroid stimulating hormone suppression time on cardiac function of patients with differentiated thyroid carcinoma. Cancer Cell Int 2018; 18: 189
• 36 la Cour JL, Hedemann-Jensen P, Sogaard-Hansen J. et al. Modeling the absorbed dose to the common carotid arteries following radioiodine treatment of benign thyroid disease. Ann Nucl Med 2013; 27: 862-866
• 37 la Cour JL, Jensen LT, Vej-Hansen A. et al. Radioiodine therapy increases the risk of cerebrovascular events in hyperthyroid and euthyroid patients. Eur J Endocrinol 2025 172: 771-778