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Antithyroid medications provide ‘disappointing’ results for treating Graves’ disease
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Radioactive iodine therapy and thyroid surgery may be more effective than antithyroid medications in helping adults with Graves’ hyperthyroidism achieve remission, according to findings published in Thyroid.
However, thyroid replacement therapy may still be required for all patients treated for Graves’ hyperthyroidism, and perceived quality of life may not improve even in patients who experience remission.
“The therapeutic possibilities for [Graves’ disease] treatment include antithyroid drugs, radioactive iodine or surgery. ... Each of the treatment modalities has specific limitations in effectiveness and possible adverse effects,” Gabriel Sjölin, MD, of the faculty of medicine and health at Örebro University Hospital in Örebro, Sweden, and colleagues wrote. “The choice of therapy for [Graves’ disease], consequently, requires the clinician to carefully consider both short- and long-term efficacy and risks in the discussion on therapeutic choices with the patient to ultimately decide which modality they prefer.”
Sjölin and colleagues identified treatment plans and outcomes across a mean follow-up of 8 years in the medical records of 1,186 adults (mean age, 46.9 years; 82% women) with Graves’ disease hyperthyroidism or toxic nodular goiter diagnosed between 2003 and 2005. These patients also completed questionnaires pertaining to quality of life at follow-up.
Among the cohort, 65.3% were initially treated with antithyroid medications, such as methimazole or propylthiouracil. With 45.3% of this group achieving remission and 40.3% maintaining thyroid function at follow-up and avoiding thyroid replacement therapy, “the effects of [antithyroid drug] treatment to produce long-term remission in [Graves’ disease] in particular are disappointing,” the researchers wrote.
In addition, ablative treatment was required for 23% of those who were initially treated with antithyroid medications but did not maintain a full regimen. During follow-up, the researchers found that ablative procedures were eventually performed on 49.7% of those initially treated with antithyroid medications.
Of those who were initially treated with antithyroid medications, 77% maintained a regimen of between 12 and 18 months, and they had a remission rate of 58.9%. During follow-up, 23% of the group needed thyroid replacement therapy. In addition, 49.9% of those who maintained two antithyroid medication regimens of between 12 and 18 months achieved remission, and 28.6% required thyroid replacement therapy. After follow-up, thyroid replacement therapy was needed by 23% of those who maintained at least one antithyroid medication regimen while normal thyroid function was achieved by 77% of this population.
More than one-quarter of participants received radioiodine therapy before any other treatment (27.3%). The remission rate for these individuals was 81.5%, although the researchers noted that 83.2% eventually required thyroid replacement therapy.
Surgery was the initial treatment for 54 patients (4.6%) and resulted in a remission rate of 96.3%. An additional 224 patients underwent surgery at some point during the study and 95.3% of those who underwent surgery required thyroid replacement therapy.
Full recovery was not indicated In the questionnaires, 25.3% of the participants reported they did not achieve full recovery, including 36% of those on thyroid replacement therapy and 18.9% of those who did not need thyroid replacement (P < .001).
“The risk of hypothyroidism in a [Graves’ disease] population many years after [antithyroid drug] therapy is highly significant and needs to be disclosed as a possible risk when a new patient with Graves' hyperthyroidism is advised on choice of treatment,” the researchers wrote. “Our study demonstrates that treatment for Graves' hyperthyroidism has long-term consequences for many patients and reinforces the fact that [Graves’ disease] is both a serious condition, as well as the chronic nature of this disease.” – by Phil Neuffer
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Onyebuchi Okosieme, MD, FRCP
Patients with Graves’ disease have an increased risk for death and cardiovascular disease, which is reduced by early and effective therapy. The efficacy and side effect profiles of the treatment modalities — antithyroid drugs, radioactive iodine and surgery — are well-established, but the choice of primary therapy remains contentious, largely driven by disparate regional traditions. Most treatment efficacy data are based on short-term studies in small cohorts. In this study Sjölin and colleagues present efficacy and quality-of-life data for a Swedish cohort of 1,186 patients followed up for 6 to 10 years after diagnosis.
About 65% of patients were treated with antithyroid drugs initially. Remission rates after the first course of drugs was 45% rising to 49% in total after two treatment courses. As expected, cure rates for radioactive iodine and surgery were significantly higher at 82% and 96%, respectively. Overall, normal thyroid status without levothyroxine supplementation was only achieved in a third of the cohort, and surprisingly, 23% of patients who received antithyroid drugs alone still required levothyroxine.
The strength of the study is the large number of patients with long-term prospective follow-up, although 40% of the invited cohort declined to participate, raising a risk for bias. Nonetheless, these findings will be useful in planning treatment for Graves’ disease patients. As in most of Europe and Asia, the data highlight a preference for primary therapy with antithyroid drugs despite their generally dismal overall remission rates.
The challenge for clinicians will now be to identify which patients are unlikely to respond to antithyroid drugs and to offer definitive treatment to such patients from the outset. A number of useful clinical predictive scores for antithyroid drug treatment response are in existence but will need further validation. Ultimately, a personalized treatment approach will improve morbidity and mortality outcomes.
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