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: 6.21). 06/2007; 92(6):2157-62. DOI: 10.1210/jc.2006-2135
Source: PubMed


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.

Download full-text


Available from: Jaeduk Yoshimura Noh,
187 Reads
  • Source
    • "Carbimazole, which is a pro-drug that is converted to MMI, can be used in place of MMI in countries where it is available. Although MMI is often prescribed in divided doses over the day, once a day dosing is sufficient [14] and is associated with better compliance than multiple daily doses [15]. The typical MMI dose is 0.2 to 0.5 mg/kg per day, and doses can range from 0.1 to 1.0 mg/kg per day [3,16-20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The most prevalent cause of thyrotoxicosis in children is Graves' disease (GD), and remission occurs only in a modest proportion of patients. Thus most pediatric patients with GD will need treatment with radioactive iodine (RAI; (131)I) or surgical thyroidectomy. When antithyroid drugs (ATDs) are prescribed, only methimazole (MMI) should be administered, as PTU is associated with an unacceptable risk of severe liver injury. If remission does not occur following ATD therapy, (131)I or surgery should be contemplated. When (131)I is administered, dosages should be greater than 150 uCi/gm of thyroid tissue, with higher dosages needed for large glands. Considering that there will be low-level whole body radiation exposure associated with (131)I, this treatment should be avoided in young children. When surgery is performed near total or total-thyroidectomy is the recommended procedure. Complications for thyroidectomy in children are considerably higher than in adults, thus an experienced thyroid surgeon is needed when children are operated on. Most importantly, the care of children with GD can be complicated and requires physicians with expertise in the area.
    International Journal of Pediatric Endocrinology 06/2014; 2014(1):10. DOI:10.1186/1687-9856-2014-10
  • Source
    • "Adverse events on MMI treatment generally occur during the first six months of therapy [32]. MMI is also more effective than PTU in the short term [33] and presents a major advantage over PTU in terms of compliance, as MMI has a longer half-life and is effective when given as a single daily dose. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Graves' disease is an autoimmune disorder resulting from thyrotropin receptor stimulation by autoantibodies. It may occur at any age during childhood, but its frequency increases with age, peaking during adolescence. Symptoms and signs are often recognizable and proportional to the increase in serum free thyroid hormone levels. Antithyroid drug treatment with methimazole (or carbimazole) is recommended for initial treatment, but relapse rates are high, with remission achieved in only 30% of children after a first course of treatment for about two years. More prolonged medical treatment may increase the remission rate to up to 50%. Alternative treatments, such as radioactive iodine or thyroidectomy, are considered in cases of relapse, lack of compliance or antithyroid drug toxicity. Relapse risk decreases with increasing duration of the first course of antithyroid drug treatment. The identification of other predictive factors, such as severe biochemical hyperthyroidism at diagnosis, young age and the absence of other autoimmune conditions, has made it possible to stratify patients according to the risk of relapse, leading to improvements in patient management, by facilitating the identification of patients requiring long-term antithyroid drug treatment or early alternative therapy.
    03/2014; 28(2):233-243. DOI:10.1016/j.beem.2013.08.008
  • Source
    • "ATDs are associated with a rather high frequency of adverse events; hepatotoxicity, cutaneous reactions, and agranulocytosis are the main adverse events [3]. Frequencies of adverse events in Japanese GD patients after initial ATD treatment have recently been reported [3] [4], and according to the reports the percentage of patients with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels more than twice the upper limit of the reference range was 25.8–26.9% among patients treated with PTU as opposed to 6.6–9.0% "
    [Show abstract] [Hide abstract]
    ABSTRACT: The frequency and types of adverse events after initial antithyroid drug (ATD) therapy during pregnancy have never been reported, nor has whether the frequency of adverse events is the same as among nonpregnant subjects ever been investigated. We investigated retrospectively the frequency of adverse events after initial ATD administration to previously untreated Graves' disease (GD) patients during pregnancy. We reviewed the charts of cases of 91 untreated pregnant women who came to our hospital for the first time and were newly diagnosed with GD during the period between January 1, 1999, and December 31, 2011. Thiamazole (MMI) was used to treat 40 patients and 51 patients were treated with propylthiouracil (PTU). Adverse events occurred in 5 patients (5/40; 12.5%) treated with MMI, and they consisted of cutaneous reactions in 5 patients. Adverse events occurred in five patients (5/51; 9.8%) treated with PTU, and they consisted of hepatotoxicity in two patients and cutaneous reactions in three patients. No patients experienced agranulocytosis or ANCA-related vasculitis. Comparison with the expected rate of adverse events in nonpregnant individuals showed that the frequency of adverse events in pregnant individuals was low.
    Journal of Thyroid Research 01/2014; 2014:952352. DOI:10.1155/2014/952352
Show more