Treatment of atrial fibrillation associated with hyperthyroidism by amiodarone and methimazole

We treated a 78-year-old patient with hyperthyroidism and atrial fibrillation with amiodarone 1200 mg/day for 3 days and methimazole 60 mg/day. Sinus rhythm was restored within 3 days and serum levels of triiodothyroxine returned to normal within 4 days. A transient increase in serum rT3 concentrations was observed. Amiodarone associated with methimazole was useful in the management of atrial fibrillation and hyperthyroidism in our patient.     

Intravenous methimazole in the treatment of refractory hyperthyroidism.

BACKGROUND: Management of a hyperthyroid patient unable to take oral or rectal medication is a difficult clinical problem. The need for an alternative parenteral route of antithyroid medication administration in thyrotoxic patients occurs in certain rare cases, such as emergent gastrointestinal surgery, bowel ileus or obstruction, or severe vomiting and diarrhea. We report a simple and successful protocol for the preparation and use of intravenous methimazole (MMI) for treatment of hyperthyroidism in patients intolerant of orally and rectally administered thionamides. METHODS: Five hundred milligrams of methimazole USP powder was reconstituted with pH-neutral 0.9% sodium chloride solution to a final volume of 50 mL using aseptic technique, then filtered through a 0.22-microm filter. MMI injection was administered as a slow intravenous push over 2 minutes and followed by a saline flush. CASES: A 76-year-old man, intolerant of oral and rectal medications because of an ileus and intractable diarrhea, who developed worsening thyrotoxicosis after an emergent spinal cord decompression, and a 42-year-old man with chronic liver disease and hyperthyroidism, requiring emergent exploratory laparotomy and maintenance of complete bowel rest because of persistent gastrointestinal bleeding were rendered euthyroid using intravenous MMI. CONCLUSION: Two cases of hyperthyroidism successfully treated with a preparation of intravenous MMI are described.     

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

CONTEXT: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: Patients newly diagnosed with GD were randomly assigned to one of the three treatment regimens in a prospective study at four Japanese hospitals. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.     

Treatment of hyperthyroidism with a small single daily dose of methimazole

A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 +/- 2.8 and 6.0 +/- 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).     

Glucagon binding autoantibodies in a patient with hyperthyroidism treated with methimazole

A 47-yr-old woman who had previously received methimazole (MMI) treatment for hyperthyroidism was found to have glucagon binding autoantibodies in plasma. She had never received glucagon. The binding substances were detected in plasma at the time of a glucagon RIA. [125I]Glucagon binding was inhibited only by porcine glucagon and porcine glicentin, and dissociated at acid pH. The substances proved to be glucagon binding antibodies (immunoglobulin G, L-chain K-type), as determined by ammonium sulfate and radioprecipitation. There were no clinical manifestations related the presence of these autoantibodies. In a survey of 91 patients with thyroid disease, 3 patients whose plasma bound [125I]glucagon were identified among 41 with hyperthyroidism who were receiving MMI treatment. Such binding was not found in plasma from untreated hyperthyroid patients, those receiving propylthiouracil or those with chronic thyroiditis. These findings suggest that the development of glucagon antibodies in hyperthyroidism may be associated with MMI treatment.     

小剂量甲巯咪唑治疗亚临床甲状腺功能亢进症合并阵发性房颤的临床观察

应用小剂量甲巯咪唑+比索洛尔治疗27例亚临床甲状腺功能亢进症合并阵发性房颤患者,治疗前后均接受多普勒超声心动仪、24 h动态心电图检查,放射免疫法测定血清FT3、FT4及TSH,观察期3个月,结果显示治疗后患者左室舒张功能明显改善(P<0.01),窦性心律维持率高,甲减发生率低,提示小剂量甲巯咪唑治疗亚临床甲状腺功能亢进症合并阵发性房颤安全有效.

Abstract：

Twenty-seven patients with subclinical hyperthyroidism(SH)complicated by paroxysmal atrial fibrillation(PAF)were treated with methimazole plus bisoprolol.All patients were examined by Doppler echocardiogram and 24 h ambulatory electrocardiograms before and 3 months after treatment.Serum FT3,FT4,and TSH levels were measured with RIA.The results showed that low-dose methimazole therapy could improve the left ventricular diastolic function(P < 0.01)and help maintain sinus rhythm.The incidence of subclinical hypothyroidism was low.Low-dose methimazole was effective and safe in patients with SH complicated by PAF.     

Effect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine

OBJECTIVE: To investigate the long-term effects of continuous methimazole (MMI) therapy. DESIGN AND METHODS: Five hundred and four patients over 40 years of age with diffuse toxic goiter were treated with MMI for 18 months. Within one year after discontinuation of MMI, hyperthyroidism recurred in 104 patients. They were randomized into 2 groups for continuous antithyroid and radioiodine treatment. Numbers of occurrences of thyroid dysfunction and total costs of management were assessed during 10 years of follow-up. At the end of the study, 26 patients were still on continuous MMI (group 1), and of 41 radioiodine-treated patients (group 2), 16 were euthyroid and 25 became hypothyroid. Serum thyroid and lipid profiles, bone mineral density, and echocardiography data were obtained. RESULTS: There was no significant difference in age, sex, duration of symptoms and thyroid function between the two groups. No serious complications occurred in any of the patients. The cost of treatment was lower in group 1 than in group 2. At the end of 10 years, goiter rate was greater and antithyroperoxidase antibody concentration was higher in group 1 than in group 2. Serum cholesterol and low density lipoprotein-cholesterol concentrations were increased in group 2 as compared with group 1; relative risks were 1.8 (1.12-2.95, P<0.02) and 1.6 (1.09-2.34, P<0.02) respectively. Bone mineral density and echocardiographic measurements were not different between the two groups. CONCLUSION: Long-term continuous treatment of hyperthyroidism with MMI is safe. The complications and the expense of the treatment do not exceed those of radioactive iodine therapy.     

A case of severe cholestatic jaundice with hyperthyroidism successfully treated with methimazole

Liver dysfunction is a common complication observed in patients with hyperthyroidism, however the dysfunction is always mild and obvious jaundice is rarely observed. We present the case of a 43-year-old man who suffered from hyperthyroidism complicated by severe jaundice. The jaundice likely occurred as a secondary consequence of cholestasis due to hyperthyroidism, since other causes such as drug-induced or autoimmune liver dysfunction were ruled out. Treatment with methimazole improved severe cholestatic jaundice in parallel with normalization of thyroid function. The mechanism of cholestasis as a secondary complication of hyperthyroidism has not been uncovered and there is no specific biochemical marker for cholestasis due to this hormonal disease at present. This case serves as a reminder that severe jaundice can be a manifestation of simple hyperthyroidism, and that administration of antithyroid drugs is an effective treatment for severe cholestatic jaundice in such cases.     

甲状腺功能亢进性肝损害与甲巯咪唑继发性肝损害的临床比较研究

目的分析甲状腺功能亢进症(简称甲亢)性肝损害患者的肝功能与甲状腺功能的相关性,探讨抗甲亢药物甲巯咪唑所致肝损害患者的临床特征及其引起肝损害的相关因素。方法纳入甲亢性肝病患者54例(甲亢性肝损害组)和初诊未治的无肝损害甲亢患者33例(甲亢无肝损害组),收集两组患者用药前的一般资料和临床资料(甲状腺功能和肝功能),分析甲亢性肝损害的相关因素;将同期抗甲亢药物甲巯咪唑致肝损害患者(27例)根据肝功能指标分为肝细胞型组(7例)、胆汁淤积型组(12例)和混合型组(8例),收集其一般资料和临床资料(甲状腺功能和肝功能)并比较。结果甲亢性肝损害组患者治疗前的ALT、AST、碱性磷酸酶(ALP)、谷氨酰转肽酶(γ-GT)、总胆红素(TBIL)、游离三碘甲腺原氨酸(FT 3)、游离甲状腺激素(FT 4)和促甲状腺激素受体抗体(TRAb)水平明显高于甲亢无肝损害组(P<0.05),两组患者ALT、ALP、γ-GT水平均与FT 3、FT 4、TRAb水平呈明显正相关(P<0.05)。肝细胞型组、胆汁淤积型组和混合型组患者的年龄、用药时间、ALT、ALP比较差异均有统计学意义(P<0.05)。结论甲亢患者甲状腺功能异常的严重程度可能与其肝损害相关;抗甲亢药物甲巯咪唑引起的肝损害类型可能与患者年龄、病程及用药时间有关。     

Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism

In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 micrograms. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pre-treatment study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone mineralization and calciotropic hormones in children with hyperthyroidism. Effects of methimazole therapy

We studied bone mineralization and calcium homeostasis in two children with hyperthyroidism before and during 3 yr of methimazole therapy in order to evaluate the effects of thyrotoxicosis and its therapy on mineral metabolism. Case 1, female, 4.1 year old with hyperthyroidism from 6 months. Biochemical data: increased thyroid function, phosphate and osteocalcin, decreased 1,25(OH)2D levels. X-ray: severe osteoporosis; bone mineral content (BMC) -23.0%, BMC/BW -25.1%. Case 2, female, 7.4 year old with hyperthyroidism from 9 months. Biochemical data: thyroid function, ionized calcium and osteocalcin were increased, 1,25(OH)2D and intact PTH were decreased. X-ray: severe osteoporosis: BMC -32.8%, BMC/BW -36.0. After the patients were euthyroid, they showed an increase of 1,25(OH)2D and intact PTH into normal values and a fall in calcium and phosphate. Osteocalcin levels returned in normal range one yr after first evaluation. Bone mineral analysis showed no variation of BMC and BMC/BW in the first 6 months of therapy and an increase in the following 6 months. In the following two years BMC and BMC/BW rose to normal range. Our study provides further evidence that in hyperthyroidism an altered mineral homeostasis is present with a reversible disturbance in vitamin D metabolism. We found that the return to euthyroidism was associated with a normalization of mineral homeostasis and with a recovery of bone mineralization. Osteocalcin assay may be an useful index to monitor bone metabolism in hyperthyroidism.     

Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves' hyperthyroidism

OBJECTIVE: The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves' hyperthyroidism. BACKGROUND: Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels. METHODS: Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study. CONCLUSION: During the 12-week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves' hyperthyroidism.     

Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves' hyperthyroidism

Radioiodine (131I) is the preferred definitive treatment for Graves' hyperthyroidism. Pretreatment with antithyroid drugs is often used to avoid thyroid hormone discharge after 131I ablation. However, this may represent an unnecessary increase in risk and costs. Fifty-one patients with Graves' disease were randomly assigned to receive 131I alone (28 patients) or 131I plus pretreatment with methimazole (30 mg/day; 23 patients). Methimazole was interrupted 4 days before 131I therapy. Serum T4, free T4 (FT4), and T3 were measured on days -4 and -1, on the day of treatment, and on days 2, 5, 7, 14, 20, and 30. In patients receiving 131I alone, mean serum T4 levels did not change after therapy. Mean serum FT4 and T3 levels decreased significantly 5 days after 131I administration (15% and 18%, respectively). Serum T3 reached its lowest level on day 30 (38%). With pretreatment, mean serum T4, FT4, and T3 levels increased (38%, 39%, and 70%, respectively) after methimazole discontinuation and before 131I administration. After 131I, serum T4 levels peaked on day 7 (23% vs. treatment day; 70% vs. baseline); FT4 levels peaked on day 14 (53% vs. treatment day; 107% vs. baseline). The serum T3 concentration increased 9% on day 2 (85% vs. baseline) and decreased from day 14 (15%) to day 30 (21%). We conclude that interruption of antithyroid drugs causes a short term increase in serum thyroid hormone levels in patients with Graves' hyperthyroidism receiving 131I. Thyroid hormone levels stabilize or decrease during the first 30 days after 131I therapy.