CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.