Antithyroid Drugs Effective as Initial Treatment for Graves’ Hyperthyroidism

Antithyroid drug treatment (ATD) is effective as initial therapy for Graves’ hyperthyroidism, and independent risk factors may predict the optimal treatment period for each patient, according to a study published in the European Thyroid Journal.

Researchers sought to evaluate the efficacy of ATD in patients with Graves’s hyperthyroidism. A historical cohort study was conducted with patients newly diagnosed with Graves’ hyperthyroidism (N=3633) between 2005 and 2018. Patients with poor compliance, short ATD treatment duration, and insufficient follow-up duration were excluded. After exclusion criteria were applied, 1829 patients were enrolled in the study (median age of 45 years, 69% female). Patients were started on methimazole (MMI), carbimazole (CAM), and propylthiouracil (PTU), and ATD was discontinued when levels were normalized. Patients were also treated with surgery and radioactive iodine (RAI) therapy.

Remission was defined as euthyroid status for over 12 months after ATD discontinuation and recurrence was defined as continually suppressed thyroid stimulating hormone (TSH) levels during follow-up after ATD discontinuation. A patient’s recurrence-free survival (RFS) was defined as the amount of time from ATD discontinuation until recurrence or the last follow-up. Variables were compared using Wilcoxon rank-sum and chi-square tests. Kaplan-Meier curves were used to estimate survival, and the log-rank tests determined significance. Risk factors were evaluated using the Cox proportional hazard model. 

Of the total 1829 patients, 56.5% received MMI and 7.2% received PTU as first-line therapy. At baseline, the median free triiodothyronine (fT3) levels were 2.5 ng/dL, and TRAb was 9.8 IU/L. Initially, most patients (93.9%) underwent ATD therapy, 3.7% of patients underwent surgery, and 2.3% received RAI therapy. Of the patients who underwent ATD, 1235 discontinued their therapy with a median duration of 55.4 months. 

The researchers observed remission in 687 (55.6%) patients and recurrence in 548 (44.4%) patients. Most patients with recurrent hyperthyroidism (95.4%) underwent a second ATD therapy, of which 124 (54.1%) patients had a second remission, and 105 (45.9%) had an additional recurrence. After a median follow-up of 67.5 (IQR, 46-101) months, 10.5% of patients underwent RAI therapy and 7.7% underwent surgery. The researchers observed that 48.5% of patients withdrew from ATD and 29.3% were still on ATD therapy. 

The researchers also observed risk factors associated with recurrence and TRAb level changes. The recurrence group (median age 44 years) was reportedly older than the remission group (P <.001) and had more smokers who were male (P =.01, P =.02, respectively). In the univariate analysis, male patients who smoked, aged younger than 45, and had thyroid-associated ophthalmopathy were inversely associated with RFS. A positive TRAb level was associated with a shorter RFS (HR, 1.91; 95% CI, 1.60-2.27; P <.001) at ATD discontinuation. In the multivariate analysis, factors such as an age younger than 45 years (HR, 1.31; 95% CI, 1.11-1.56; P =.002), male gender (HR, 1.25; 95% CI, 1.04-1.51; P =.03), and changing TRAb trajectories (P <.001) were all associated with shorter RFS. 

Limitations of this study included possible bias due to the study’s retrospective design and discrepancies in patient compliance, which might have influenced TRAb patterns. 

The researchers concluded “ATD is a considerable option for the initial treatment of Graves’ hyperthyroidism as well as for recurrent disease.”