Long-term Cardiovascular Morbidity and Mortality in Patients Treated for Differentiated Thyroid Cancer

Nelli Pajamäki; Saara Metso; Tommi Hakala; Tapani Ebeling; Heini Huhtala; Essi Ryödi; Juhani Sand; Arja Jukkola-Vuorinen; Pirkko-Liisa Kellokumpu-Lehtinen; Pia Jaatinen


Clin Endocrinol. 2018;88(2):303-310. 

In This Article

Abstract and Introduction


Objectives Thyroid hormone suppression therapy has been widely used in the treatment of thyroid cancer, but concerns have been raised about the cardiovascular risks of this treatment. The objective of this study was to evaluate long-term cardiovascular morbidity and mortality in patients treated for differentiated thyroid cancer (DTC) and to assess the effect of TSH suppression and radioiodine (RAI) treatment on the cardiovascular outcome.

Design Retrospective cohort study.

Patients and measurements Patients (n = 901) treated for DTC between 1981 and 2002 at 2 Finnish University hospitals were compared with a randomly chosen reference group (n = 4485) matched for age, gender and the place of residence. Kaplan-Meier and Cox regression analyses were used to estimate the risk of morbidity or death due to different cardiovascular diseases (CVD) after the diagnosis of DTC.

Results Morbidity due to any CVD (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.05–1.28) and due to all arrhythmias (HR 1.25, CI 1.06–1.48) and atrial fibrillation (AF) (HR 1.29, CI 1.06–1.57) was more frequent in the DTC patients than in the controls. The increased cardiovascular morbidity was confined to patients with a mean TSH level below 0.1 mU/L (HR 1.27, CI 1.03–1.58) and to those treated with RAI (HR 1.18, CI 1.05–1.31). Cardiovascular mortality, however, was lower among the patients than the controls (HR 0.73, CI 0.58–0.92), due to a lower mortality from coronary artery disease.

Conclusions Differentiated thyroid cancer patients have an increased CVD morbidity, which is mostly accountable to AF and to TSH suppression below 0.1 mU/L.


Differentiated thyroid cancer (DTC) includes papillary and follicular thyroid cancer and represents over 90% of all thyroid cancers detected.[1] The incidence of thyroid cancer has increased over the past few decades; in the USA, the incidence has nearly tripled between the years 1975 and 2009.[2,3] The increasing incidence of thyroid cancer has been explained by early diagnosis leading to a growing number of small papillary thyroid cancers, which have an excellent prognosis.[2,3] The increased use of neck area imaging may reveal incidental thyroid cancers with no effect on survival.[4,5] Despite the increased incidence, mortality from thyroid cancer has remained stable.[2]

Diagnosis of small low-risk tumours may expose the patients to aggressive cancer treatment, which may have unfavourable long-term effects.[3] Thyroid hormone suppression therapy (THST) by levothyroxine has been traditionally used as a treatment of thyroid cancer to improve the outcome, but recently the necessity and safety of this treatment in low-risk patients have been questioned.[6,7] There are concerns about the long-term cardiovascular effects of THST-induced iatrogenic thyrotoxicosis,[6,7] as the risks of endogenous hyperthyroidism are well known.[8]

Increased cardiovascular mortality and an increased risk of atrial fibrillation (AF) have been reported among DTC patients.[9–12] An association between a low TSH level and an increased risk of cardiovascular mortality has been found in patients treated for DTC.[9] THST has been reported to increase myocardial strain, left ventricular mass and diastolic dysfunction, to impair arterial elasticity and to induce prothrombotic changes in DTC patients.[13–16] The most recent guidelines on DTC recommend weighing the potential benefits of THST against the possible harms of stringent TSH suppression.[17–19] For the time being, the appropriate degree of TSH suppression remains unsettled, and there are discrepancies between different guidelines.[17–19]

The aim of this study was to evaluate the long-term cardiovascular morbidity and mortality in DTC patients. The secondary aim was to assess the effect of the TSH suppression level and radioiodine (RAI) treatment on the cardiovascular outcome of the patients.