Regardless of the method used, an early and intensive treatment approach to hyperthyroidism in Graves disease is associated with improvements in cardiovascular morbidity and all-cause mortality, according to study results published in The Lancet Diabetes & Endocrinology.

This retrospective cohort study was designed to assess initial therapy choices for patients with Graves disease by identifying associations between treatment method and long-term cardiovascular morbidity and all-cause mortality. From a cohort of patients diagnosed with hyperthyroidism between January 1998 and December 2013 in South Wales, United Kingdom, patients with Graves disease were identified using a thyroid-stimulating hormone (TSH) receptor antibody test register. Participants’ clinical data were linked to study outcomes using the All-Wales Secure Anonymised Information Linkage Databank. The study had no exclusion criteria, and participants were age- and sex-matched 1:4 to a control population within the same database.

Participants with Graves disease were grouped by primary treatment method: patients who received only antithyroid drugs, patients who received radioiodine with resolved hyperthyroidism (radioiodine group A), or patients who received radioiodine with unresolved hyperthyroidism group (radioiodine group B), with a landmark set for 1 year after diagnosis. Cox and Kaplan-Meier regression models were used to evaluate associations between treatment method and all-cause mortality and cardiovascular morbidity (heart failure, myocardial infarction, ischemic stroke, or death). In addition, Cox regression models were used to analyze associations between TSH concentration and outcomes, and cubic-spline regression models were used to analyze associations between free thyroxine concentration and outcomes.

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Patient-level data were extracted for 4189 patients with Graves disease (81.5% female) and 16,756 controls (81.5% female). The antithyroid drug group had 3587 participants, the radioiodine group A had 250 participants, and the radioiodine group B had 182 participants. Compared with controls, participants with Graves disease had increased all-cause mortality (hazard ratio [HR], 1.22; 95% CI, 1.05-1.42). Mortality was lower in radioiodine group A (HR, 0.50; 95% CI, 0.29-0.85) compared with the antithyroid drug group, but was higher in radioiodine group B (HR, 1.51; 95% CI, 0.96-2.37) compared with the antithyroid drug group. Regardless of treatment method, persistently low concentrations of TSH 1 year after diagnosis were associated with increased mortality (HR, 1.55; 95% CI, 1.08-2.24) and a positive nonlinear relationship was shown between free thyroxine concentrations at 1 year and all-cause mortality.

Study investigators concluded that “early and intensive control of hyperthyroidism in [Graves disease] is associated with improvements in long-term cardiovascular morbidity and all-cause mortality, regardless of the treatment method. Increased emphasis should be placed on ensuring prompt elimination of hyperthyroidism and maintenance of a normal thyroid status in the management of [Graves disease].”

Several authors declared affiliations with the pharmaceutical industry. Please refer to the original reference for a complete list of disclosures.

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Reference

Okosieme OE, Taylor PN, Evans C, et al. Primary therapy of Graves’ disease and cardiovascular morbidity and mortality: a linked-record cohort study [published online February 28, 2019]. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(19)30059-2