Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease

Department of Internal Medicine II, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka, Japan.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.31). 06/2007; 92(6):2157-62. DOI: 10.1210/jc.2006-2135
Source: PubMed

ABSTRACT Although methimazole (MMI) and propylthiouracil (PTU) have long been used to treat hyperthyroidism caused by Graves' disease (GD), there is still no clear conclusion about the choice of drug or appropriate initial doses.
The aim of the study was to compare the MMI 30 mg/d treatment with the PTU 300 mg/d and MMI 15 mg/d treatment in terms of efficacy and adverse reactions.
Patients newly diagnosed with GD were randomly assigned to one of the three treatment regimens in a prospective study at four Japanese hospitals.
Percentages of patients with normal serum free T(4) (FT4) or free T(3) (FT3) and frequency of adverse effects were measured at 4, 8, and 12 wk.
MMI 30 mg/d normalized FT4 in more patients than PTU 300 mg/d and MMI 15 mg/d for the whole group (240 patients) at 12 wk (96.5 vs. 78.3%; P = 0.001; and 86.2%, P = 0.023, respectively). When patients were divided into two groups by initial FT4, in the group of the patients with severe hyperthyroidism (FT4, 7 ng/dl or more, 64 patients) MMI 30 mg/d normalized FT4 more effectively than PTU 300 mg/d at 8 and 12 wk and MMI 15 mg/d at 8 wk, respectively (P < 0.05). No remarkable difference between the treatments was observed in patients with initial FT4 less than 7 ng/dl. Adverse effects, especially mild hepatotoxicity, were higher with PTU and significantly lower with MMI 15 mg/d compared with MMI 30 mg/d.
MMI 15 mg/d is suitable for mild and moderate GD, whereas MMI 30 mg/d is advisable for severe cases. PTU is not recommended for initial use.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.
    PLoS ONE 10/2014; 9(10):e109753. DOI:10.1371/journal.pone.0109753 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but serious complication of ATD therapy. The characteristics of severe hepatotoxicity have been reported in only a small number of patients. Method: We studied 90 patients with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000-2013) who were about to undergo nuclear medicine therapy with 131I from a sample of 8864 patients with hyperthyroidism, and we evaluated the outcomes. Results: The mean age of the patients with ATD-induced severe hepatotoxicity was 41.6±12.5 years (mean±SD), and the female to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1±7.4 mg/d. The propylthiouracil (PTU) dose given at the onset was 212.8±105.0 mg/d. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The types of severe hepatotoxicity did not differ between the MMI and PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these frequencies were not significantly different (p=0.069). The patients who took 131I received an average dose of 279.1±86.1 MBq (n=84). Therapy was successful in 60 of the 67 patients (89.6%). The success rate was equivalent (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31). Conclusions: Severe hepatotoxicity tends to occur within the first three months after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did not differ between the MMI and PTU groups. 131I therapy is an effective treatment approach for patients with ATD-induced severe hepatotoxicity.
    Thyroid: official journal of the American Thyroid Association 11/2014; 25(3). DOI:10.1089/thy.2014.0350 · 3.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Graves' disease (GD) accounts for 10%-15% of thyroid disorders in children and adolescents. The use of antithyroid drugs as the initial treatment option in GD is well accepted. An average two years remission is achieved in about 30% of children treated with antithyroid drugs. However, the optimal treatment duration and the predictive marker of remission after antithyroid drug therapy are still controversial. Additionally, (131)I therapy and surgery are considered the option for treatment in children and adolescents with GD. We review the treatment options for pediatric GD and the possible determinants of remission and relapse on antithyroid drug treatment in children and adolescents.
    09/2014; 19(3):122-6. DOI:10.6065/apem.2014.19.3.122

Full-text (2 Sources)

Available from
May 21, 2014