Thyroidectomy as first-line treatment for Graves’ disease reduces mortality, CVD risk
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Adults who underwent a thyroidectomy as first-line treatment for Graves’ disease had lower risks for all-cause mortality and cardiovascular disease than those treated with antithyroid drugs or radioactive iodine, according to study data.
Thyroidectomy also lowered the risks for atrial fibrillation, diabetes and hypertension, and was associated with lower 10-year health care costs owing to a lower relapse rate compared with antithyroid drugs or radioactive iodine, according to researchers.
“This study lends support to an increased role of surgery as a first-line treatment in Graves’ disease,” Brian H.H. Lang, MBBS, MS, clinical professor and director of the Surgical Skills Training Center in the department of surgery at the University of Hong Kong, and colleagues wrote in a study published in Annals of Surgery.
Researchers conducted a retrospective cohort study of 6,385 adults (mean age, 45.6 years; 72.6% women) with a diagnosis of Graves’ disease in the Hong Kong Hospital Authority Clinical Management System who received first-line treatment with antithyroid drugs, radioactive iodine or thyroidectomy from 2006 to 2018. Adults receiving antithyroid drugs for more than 1 year were placed into the antithyroid drugs group (n = 4,784). The radioactive iodine group included those who received antithyroid drugs for less than 1 year or not at all, followed by radioactive iodine therapy (n = 1,274). The thyroidectomy group included those who had thyroidectomy preceded by less than 1 year of antithyroid drugs or no treatment with antithyroid drugs (n = 327). Primary outcomes included risks for CVD, atrial fibrillation, psychological disease, diabetes, hypertension and all-cause mortality after treatment. Additional outcomes included 10-year direct cumulative health care costs and changes in comorbidity profile.
Thyroidectomy lowers risk for mortality, CVD
Compared with adults receiving only antithyroid drug therapy, those who underwent a thyroidectomy had lower risks for all-cause mortality (HR = 0.363; 95% CI, 0.332-0.396), CVD (HR = 0.216; 95% CI, 0.195-0.239), atrial fibrillation (HR = 0.103; 95% CI, 0.085-0.124), psychological disease (HR = 0.279; 95% CI, 0.258-0.301), diabetes (HR = 0.341; 95% CI, 0.305-0.381) and hypertension (HR = 0.673; 95% CI, 0.632-0.718). Adults in the radioactive iodine group had lower risks for all-cause mortality (HR = 0.931; 95% CI, 0.882-0.982), CVD (HR = 0.784; 95% CI, 0.742-0.828), atrial fibrillation (HR = 0.622; 95% CI, 0.578-0.67) and psychological disease (HR = 0.895; 95% CI, 0.855-0.937), and higher risks for diabetes (HR = 1.081; 95% CI, 1.014-1.152) and hypertension (HR = 1.255; 95% CI, 1.203-1.31) than those receiving only antithyroid drugs. Compared with radioactive iodine therapy, adults who underwent a thyroidectomy had lower risks for all-cause mortality (HR = 0.446; 95% CI, 0.408-0.487), CVD (HR = 0.296; 95% CI, 0.267-0.328), atrial fibrillation (HR = 0.256; 95% CI, 0.212-0.308), psychological disease (HR = 0.303; 95% CI, 0.28-0.327), diabetes (HR = 0.269; 95% CI, 0.242-0.3) and hypertension (HR = 0.555; 95% CI, 0.523-0.589).
Lower 10-year health care costs with thyroidectomy
The thyroidectomy group had a lower relapse rate (2.41%) compared with radioactive iodine therapy (19.53%) or antithyroid drug treatment (75.6%). For those receiving radioactive iodine therapy, two doses of treatment increased the likelihood for all-cause mortality (OR = 2.79; 95% CI, 1.761-4.422) and hypertension (OR = 1.793; 95% CI, 1.125-2.858) compared with those receiving only one dose.
Adults who underwent thyroidectomy had the highest annual health care expenses in the first year of follow-up. The costs among the three groups became similar by the fifth year of follow-up. After 10 years, the thyroidectomy group had a lower cumulative health cost (mean health costs, $20,202) compared with the antithyroid drug group ($23,915) and the radioactive iodine group ($24,260).
“This long-term cost-saving might have been a result of the lower relapse rate, which led to a lower chance of continuous monitoring and treatment, including definitive radioactive iodine and surgery later,” the researchers wrote. “Regarding cost-effectiveness as an important factor for consideration in the choice of Graves’ disease therapy, our results favored surgery with lower long-term health care costs.”
Perspective
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This is a retrospective study from Hong Kong comparing treatment of Graves’ disease by total thyroidectomy, radioactive iodine or antithyroid drugs on outcomes of all cause mortality, cardiovascular disease and other morbidities along with health care costs and relapse rates. The analysis found that total thyroidectomy was associated with lower risk for all outcomes, including lowest cost overall and lower relapse rates.
Some of these results were seen in previous studies. Is this a function of the rapid improvement in hyperthyroidism with total thyroidectomy? Lillevang-Johansen colleagues have found from their Danish cohort that increased duration of TSH suppression, even while on treatment, significantly increases risk for CVD (Lillevang-Johansen M, et al. Eur J Endocrinol. 2019;doi:10.1530/EJE-19-0006). In analysis of our Mayo Clinic database of Graves’ disease patients, most antithyroid drug-treated patients do not achieve swift biochemical normalization as seen with surgery, but more precise dosing of antithyroid drugs based on biochemical parameters, goiter size and other factors may allow for greater success in early normalization of free thyroxine.
Future studies should investigate whether such approach mitigates CVD risk, relapse and costs in antithyroid drugs as it compares to total thyroidectomy. Moreover, while the results of this analysis are intriguing, they must be interpreted in light of confounders related to surgical candidacy and selection bias. Without randomization, surgically managed patients tend to be younger, with less comorbidities and have better baseline functional status. Management of Graves’ disease should continue to be individualized to each patient’s situation through shared decision-making.
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