March 13, 2019
3 min read

Early, effective control of Graves' disease improves survival, regardless of treatment

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An early and intensive control of hyperthyroidism in Graves’ disease is associated with reduced mortality and cardiovascular risk independent of the method of treatment, according to findings from a linked-record cohort study.

Onyebuchi Okosieme

“We have shown that patients with Graves’ disease have an increased risk of mortality and cardiovascular disease, which can be reduced by effective and early control of hyperthyroidism,” Onyebuchi Okosieme, MD, FRCP, a consultant endocrinologist with Cwm Taf University Health Board in Wales and an honorary senior research fellow at Cardiff University, United Kingdom, told Endocrine Today. “Patients successfully treated with radioactive iodine in the first year of diagnosis had reduced long-term risk for mortality and major adverse cardiovascular events compared with those treated with antithyroid drugs alone or with those treated with radioiodine without control of hyperthyroidism.”

Okosieme and colleagues analyzed data from 4,189 patients with Graves’ disease diagnosed between 1998 and 2013 from a thyroid-stimulating hormone-receptor antibody (TRAb) test register in South Wales, United Kingdom (81.5% women). Researchers linked the registry data to data from the All-Wales Secure Anonymised Information Linkage (SAIL) Databank, matching patients by age and sex to a control population (n = 16,756; 81.5% women; follow-up range, 6 months to 16.8 years). Researchers stratified patients by treatment type within 1 year of diagnosis: antithyroid drug group (n = 3,587), radioiodine with resolved hyperthyroidism (radioiodine group A; n = 250) or radioiodine with unresolved hyperthyroidism (radioiodine group B; n = 182). Primary outcome was all-cause mortality, and secondary outcome was major adverse cardiac events (myocardial infarction, heart failure, ischemic stroke or death), with the landmark set at 1 year after diagnosis.

Overall, 228 patients (5.4%) with Graves’ disease died by data cutoff (Dec. 31, 2014) vs. 765 controls (4.6%). Compared with controls, all patients with Grave’s disease were 23% more likely to die of any cause (adjusted HR = 1.22; 95% CI, 1.06-1.42). Patients with Graves’ disease were also nearly 2.5 times more likely to experience a major adverse cardiac event vs. controls (aHR = 2.47; 95% CI, 2.16-2.81), and also had increased risks for atrial fibrillation, congestive cardiac failure and ischemic stroke.

When stratified by treatment, researchers found that, compared with patients in the antithyroid drug group, those in radioiodine group A had a lower mortality rate (HR = 0.5; 95% CI, 0.29-0.85) and lower risk for major adverse cardiac events (HR = 0.59; 95% CI, 0.38-0.92). However, compared with the antithyroid drug group, patients in radioiodine group B were at increased risk for major adverse cardiac events (HR = 1.52; 95% CI, 1.01-2.28), with no survival advantage, according to researchers. Results persisted in analyses excluding patients who were pregnant (n = 63) or those with borderline TRAb concentrations at diagnosis (n = 266).


Additionally, researchers found that persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR = 1.55; 95% CI, 1.08-2.24).

“Our study design distinguished treatment effects from the effects of hyperthyroidism to show that the predictor of mortality and cardiovascular morbidity is the effectiveness of primary treatment rather than the treatment method per se,” the researchers wrote. “Our analysis of TSH concentrations at 1 year shows that the excess mortality in Graves’ disease is driven by exposure to uncontrolled hyperthyroidism and that elimination of the hyperthyroid state, whether with antithyroid drugs or radioiodine, yields survival benefits.”

Okosieme said randomized controlled trials comparing mortality and CVD risk according to the three available treatments for Graves’ disease — antithyroid drugs, radioactive iodine and surgery — would be challenging to undertake due to the large number of patients and lengthy follow-up that would be required.

“Clinicians could potentially improve long-term outcomes in patients with Graves’ disease by aiming for rapid and sustained control of hyperthyroidism,” Okosieme said. “Patients who are unlikely to achieve control of hyperthyroidism with antithyroid drugs alone should be offered early treatment with radioactive iodine.” – by Regina Schaffer

For more information:

Onyebuchi Okosieme, MD, FRCP, can be reached at Cwm Taf University Health Board, Merthyr Tydfil, CF47 9DT, UK; email:

Disclosures: Health and Care Research Wales funded this study. Okosieme reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.