Evaluation of glucose tolerance in methimazole and Radioiodine treated Graves’ patients

This Article


Article Information:

Group: 2010
Subgroup: Volume 8, Issue 3, Summer
Date: June 2011
Type: Original Article
Start Page: 132
End Page: 137


  • Javad Kiani
  • Endocrine Research Center, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences, Tehran, IR.Iran
  • Vahid Yusefi
  • Endocrine Research Center, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences, Tehran, IR.Iran
  • Maryam Tohidi
  • Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR.Iran
  • Yadollah Mehrabi
  • Faculty of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, IR.Iran
  • Fereidoun Azizi
  • Endocrine Research Center, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences, Tehran, IR.Iran


      Affiliation: Endocrine Research Center, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences
      City, Province: Tehran,
      Country: IR.Iran
      E-mail: azizi@endocrine.ac.ir


Background: One of the major concerns of the administration of radioiodine is its complications. The pancreas has sodium iodine symporter and may concentrate radioiodine. Objectives: This study compared glucose tolerance in Graves’ disease patients on continuous treatment with methimazole to radioiodine-treated hypothyroid patients on levothyroxine. Materials and Methods: In this study 132 patients with Graves’ disease who had relapsed after drug therapy were studied. Fifty-nine were on long term treatment with methimazole, and 73 were radioiodine treated hypothyroid patients on levothyroxine. In each group the glucose tolerance test was performed, and serum lipid profiles and glucose, TSH, insulin concentrations, and HOMA-IR and HOMA-B values were measured. Results: No significant differences were observed in age, sex, BMI, and BP between the two groups. Mean FBS and HOMA-IR in the radioactive iodine group were higher than in the methimazole group: 94 mg/dl versus 90 mg/dl, P = 0.019 and 1.5 (1.2-2.3) versus1.3 (0.8-2.1), P = 0.045, respectively. After controlling for family history of diabetes and total cholesterol, the two groups were not significantly different on any of the dependent variables. No significant differences were found between the two groups on the HOMA-B, median 2-hour blood glucose, and serum-insulin levels. Conclusions: The results of this study indicate that radioiodine treatment had no adverse effects on glucose tolerance and insulin resistance.

Implication for health policy/practice/research/medical education:
Radioiodine and methimazole therapy of Graves’ patients have no adverse effect on glucose hemostasis.

Please cite this paper as:
Kiani J, Yusefi V, Tohidi M, Mehrabi Y, Azizi F. Evaluation of glucose tolerance in methimazole and radioiodine treated Graves’ patients. Int J Endocriol Metab. 2010;8(3):132-7.

Keywords: Glucose tolerance;Graves’ disease;Radioactive iodine

Manuscript Body:


Radioactive iodine is an isotope that emits gamma and beta rays (1) and, since its identification in 1940, is used largely for the treatment of patients with hyperthyroidism due to Graves’ disease (2). Although the response to the effect of this method is slower than drug therapy, it is still in all other respects an ideal method for treatment. Radioactive iodine is orally administrated and is excreted through the kidneys. The effects and complications resulting from administration of radioactive iodine on various tissues and organs have always been of some concern. Complications such as carcinogenesis teratogenicity and increased mortality have been suggested in the literature (3, 4).Several studies have shown leukocyte chromosomal abnormalities in patients treated with therapeutic doses of radioactive iodine (5, 6), and carcinogenesis and increased mortality are among the major concerns (79). Initially, radioactive iodine causes cell necrosis that results in an inflammatory response (10).Following administration, radioiodine may be found in many tissues, such as the salivary glands, gastric mucosa, lactating mammary glands, ovaries, placenta, choroid plexus, pancreas, and thymus (11, 12). Because the iodine concentration in plasma is very low, a mechanism is needed to concentrate this element in the thyroid; this process, called iodide trapping, is mediated by a membrane protein known as sodium iodide symporter (NIS; [13]). Although the transfer of iodine in such tissues is not dependent on TSH, numerous studies have shown that iodine organification is done by some tissues outside the thyroid. Several studies have found NIS in the pancreatic gland (14, 15) and other studies have shown localization of radioactive iodine in the pancreas (16, 17). Therefore, the accumulation of radioactive iodine in the pancreas can have harmful effects on the function of beta cells and impair glucose tolerance in such patients.


This study was designed to investigate the effects of radioactive iodine on glucose tolerance. We aimed to compare glucose tolerance in hyperthyroid patients who received radioactive iodine and developed hypothyroidism and were euthyroid on levothyroxine with the glucose tolerance of patients on continuous methimazole treatment.

3. Materials and methods

Between 1983 and 1989, 576 patients with a clinical and laboratory diagnosis of diffuse toxic goiter were treated with methimazole; of these, 51 cases did not return during treatment or preferred to have radioactive iodine treatment. Twelve patients who relapsed during treatment were treated with radioactive iodine. Of the remaining 513 patients, 104 experienced a recurrence of hyperthyroidism. Nineteen patients wanted treatment options other than those offered by random allocation and were excluded from the study, so remained 85 patients. Additionally, 47 patients with a recurrence of hyperthyroidism were added to these 85 patients. Relapse of hyperthyroidism was confirmed in all of 132 of these patients by their high T3 and T4 levels and low TSH levels; These 132 patients were divided into two groups of continuous methimazole or radioiodine treatment, one and half year after discontinuing the drug either randomly or by patient preference. All of the patients in the methimazole group (n = 59) were euthyroid and received methimazole at a dosis of 20 mg daily in the first month, 10 mg daily in the second month, and 2.5 to 10 mg in the following months. The average dose of radioactive iodine was 7.9 ± 5.1 mci with a range of 5-13 mci. The second group of patients was followed for at least 10 years after taking radioactive iodine. If hyperthyroidism relapsed, radioactive iodine therapy was administered. If TSH levels exceeded 10 mU/l, treatment with levothyroxine was begun, and dosis was adjusted to maintain serum TSH levels between 0.3 and 3 mU/l. In both groups, patients were visited every 3 months in the first year and every 6 months in the second year. During each visit, patients were examined and clinical and laboratory statuses of thyroid were determined by measurements of serum T4, T3, T3RU, and TSH.Fifty-nine patients of the methimazole group and 73 of the radioiodine group who developed hypothyroidism, were euthyroid with levothyroxine, and were successfully followed up for at least 10 years. Physical and thyroid examinations were performed, and blood pressure, heart rate, height, weight, and body mass index (BMI) were calculated. A questionnaire for personal information and previous history of drug use and diseases was completed. Serum samples were obtained after a 12- to 14-hour fast to measure serum glucose, insulin, total cholesterol, triglycerides, and HDL cholesterol. Two hours after 75 g of glucose administration (equivalent to 82.5 g of glucose monohydrate) serum glucose was measured and HOMA- IR (Homeostasis Model Assessment-Insulin Resistance) and HOMA-B (Homeostasis Model Assessment-β cell function) were calculated; additionally, T3 by radioimmunoassay (RIA) and TSH by immunoradiometric assay (IRMA) were measured using the relevant commercial kits (Isotop, Budapest, Hungary). Free T4 was measured with an enzyme-linked fluorescent immunoassay method (kit by Biomerieux, Marcy, France, and apparatus by Mini Vdas, Marcy, France). Insulin levels were measured with EIMA (Mercodia, Uppsala, Sweden) and Elisa (Sunrise,Tecan Co.Salzburg, Austria) methods. Serum glucose level was measured using enzymatic calorimeter with glucose oxidase. Total cholesterol was measured using an enzymatic calorimeter with cholesterol esterase and cholesterol oxidase, and LDL and HDL cholesterol were measured directly. Triglycerides were measured using enzymatic calorimetry with glycerol phosphate oxidase. For all these measurements the relevant commercial kits (Pars Azmoon, Tehran, Iran) and Autoanalyzer Selectra-2 (Vital Scientific Spankeren,The Netherlands) were used. Intra- and intercoefficients of variation for T3 were 3.3% and 3.6%, for free T4 were 4.6% and 4.9%, and for TSH were 5.5% and 8.5%, respectively. For biochemical parameters, coefficients of variation were 2.0% and 2.2% for glucose, 1.2% and 1.6% for LDL cholesterol, and 1.0% and 1.5% for HDL cholesterol, respectively. For triglycerides, the intra- and intercoefficients of variation were both 2.8%.

We used following formulas for HOMA-IR and HOMA- B calculations:



3.1. Data analysis

To determine the normality of the distribution of variables, the Kolmogrof Smirnof test was used. Data with normal distributions were expressed as means and standard deviations, and data without normal distributions were expressed as medians and interquartile ranges. For comparisons between two groups, t-tests were used for variables with normal distributions and for variables without normal distributions; the Mann-Whitney test was used. To compare qualitative variables between two groups, Chi square tests were used. SPSS 16 software was used to perform the statistical analyses. P values below 0. 05 were considered significant.
4. Results

Baseline characteristics including age, height, weight, BMI, waist circumference, smoking history, physical activity, and systolic and diastolic blood pressure in 132 patients are shown in Table 1. Of the 132 patients, 52 were in the methimazole group (MMI) and 73 in the radioiodine group (RAI). Age, weight, waist circumference, smoking history, and blood pressure were not significantly different between the two groups. The MMI group had a higher average height than the RAI group (P = 0.001), but the RAI group had a higher average BMI (P = 0.039). A greater percentage of patients in the RAI group had low physical activity levels (P = 0.009), whereas a greater percentage of patients in the MMI group had moderate levels of physical activity (P = 0.006). Of the 132 patients who entered the study, 4 were excluded due to lack of complete data or laboratory tests; therefore, analysis was performed on 128 patients (73 patients in the RAI group and 55 in the MMI group).

Table 2 shows the fasting and 2-hour blood glucose, insulin, HOMA-IR, HOMA-B, thyroid function tests, and lipid profiles for the RAI and MMI groups by gender. The median fasting blood-glucose levels were higher for the RAI group than the MMI group (P = 0.035 and 0.029, respectively). The median 2-hour glucose in women of the RAI group was higher than the MMI group (P = 0.014). The median insulin levels did not differ between the two groups (P = 0.169). HOMA-IR was higher in the RAI group (P = 0.036), but HOMA-B was not significantly different in the two groups. TSH and T3 were higher in the MMI group (P = 0.012 and 0.008, respectively), and FT4 was higher in the RAI group (P = 0.001). Total cholesterol, LDL cholesterol, and triglycerides were higher in the RAI group (P = 0.011, 0.019 and 0.001, respectively). HDL cholesterol was lower in the RAI group than in the MMI group (P = 0.005).

These results led to an additional exclusion of 19 patients for the next round of analyses. Specifically, of the 128 cases, 15 patients were excluded due to a previous history of diabetes mellitus, and 4 patients were excluded due to overt hyperthyroidism (FT4 > 25 or T3 > 180 and TSH < 0.2), leaving a final sample of 109 patients. The mean age in the two groups was not significantly different (P = 0.35); 81.7% of patients