Patients with thyroid cancer who undergo total thyroidectomy have a high risk for coronary heart disease (CHD) and ischemic stroke. The dose of levothyroxine also appears to play a major role in the overall risk for cardiovascular risk, say the authors of a new study.
Compared with a control group, patients with thyroid cancer had a 15% increased risk for CHD and a similar 15% increased risk for ischemic stroke.
Receiving treatment with high doses of levothyroxine also increased risk: Being in the upper two quartiles of levothyroxine therapy carried a 4- to 5-fold risk for CHD and ischemic stroke and a 2- to 2.5-fold risk for atrial fibrillation.
The findings were presented here at the Cancer Survivorship Symposium (CSS) Advancing Care and Research.
"Our study is to our knowledge the first to investigate the risk of CHD and ischemic stroke among thyroid cancer patients," said lead author Dong Wook Shin, MD, DrPH, MBA, from Seoul National University Cancer Hospital, Korea.
"Hyperthyroidism is a well-known risk factor for atrial fibrillation and ischemic stroke and has been reported to precipitate angina and myocardial infarction in patients with underlying coronary heart disease," said Dr Shin. "Therefore, we assumed that overt or subclinical hyperthyroidism induced by long-term usage of levothyroxine can be associated with cardiovascular risk."
Many patients with thyroid cancer are exposed to long-term thyroid-stimulating hormone (TSH) suppression, in many cases as a lifetime treatment.
"We found that levothyroxine doses serve as a proxy marker for TSH suppression," Dr Shin noted.
He also pointed out that the risk for thyroid cancer has increased in most industrialized countries. In the United States, the incidence has been increasing rapidly for the past 30 years, although recent datasuggest that it may be leveling off.
However, in Korea, there has been a 10-fold increase in the past decade alone, Dr Shin explained, which may be largely due to thyroid cancer screening.
In their study, Dr Shin and colleagues investigated the incidence of CHD and ischemic stroke among patients with thyroid cancer in Korea, as well as the possible pathophysiologic mechanisms involved.
Using data from the Korean National Health Insurance data, which covers approximately 97% of the entire Korean population, they identified 182,419 individuals who had undergone thyroidectomy for thyroid cancer from 2004 to 2012.
The cohort was then matched with a control group, and a Cox proportional hazards regression analysis was used to determine the relative risk for CHD and ischemic stroke. The mean follow-up period was 4.32 years.
The team found that overall, patients with thyroid cancer had an elevated risk for CHD and ischemic stroke (hazard ratio [HR], 1.15 for both).
This risk was marked in patients who underwent total thyroidectomy and among individuals who took a higher dosage of levothyroxine (HR, 1.47 for CHD and 1.56 for ischemic stroke among those who took at least 170 μg/day).
The risk for atrial fibrillation risk was also dose-dependently associated with levothyroxine dosage, he explained. "They were more likely to develop atrial fibrillation when the dose was high, but it did not seem to make a significant difference in the risk of ischemic stroke when atrial fibrillation occurred."
Overall, patients who received higher doses showed an increased risk for CHD and ischemic stroke, but there was no significant difference according to body mass index, Dr Shin added.
"More caution is suggested for the choice of thyroidectomy and TSH suppression therapy, as well as proper management for cardiovascular disease prevention," he concluded.
In a discussion of the paper, Wendy Landier, PhD, RN, an associate professor in the Department of Pediatrics at the University of Alabama School of Medicine in Birmingham, emphasized that this is a "young cancer population with an average age of only 47 years, and it's also a healthy population.
"So with only 4 years of follow-up, what are the implications of this research?" she asked. "What will happen when they age? What is the burden for them and the healthcare system?"
Another important issue was the implications for cancer survivors who are being monitored for secondary cancers.
"So we can conclude that screening for cancer and cancer surveillance have both benefits and harms — which may include adverse consequences to patients and the health system, and sometimes less may be more," Dr Landier said.
Dr Shin and coauthors have disclosed no relevant financial relationships. Dr Landier has received research funding from Merck Sharp & Dohme (institutional).
Cancer Survivorship Symposium (CSS) Advancing Care and Research. Abstract 105. Presented January 28, 2017.