Risk of recurrence at the time of withdrawal of short- or long-term methimazole therapy in patients with Graves' hyperthyroidism: a randomized trial and a risk-scoring model.

PURPOSE: In Graves' disease, administration of low-dose methimazole for more than 60 months induces higher remission rates compared with the conventional duration of 12-18 months. However, the risk of recurrence and its predictors beyond 48 months of drug withdrawal are not known. The aims of this study were to determine the risk of recurrence during 84 months after withdrawal of short- or long-term methimazole therapy and a risk stratification for recurrence of hyperthyroidism. METHODS: A total of 258 patients were treated with methimazole for a median of 18 months and randomized to discontinuation of the drug(conventional short-term group; n = 128) or continuation of the treatment up to 60-120 months(long-term group; n = 130). Patients were followed for 84 months after methimazole withdrawal. Cox proportional hazards modeling was performed to identify factors associated with relapse and develop a risk-scoring model at the time of discontinuing the treatment. RESULTS: Hyperthyroidism recurred in 67 of 120(56%) of conventionally-treated patients versus 20 of 118(17%) of those who received long-term methimazole treatment, p < 0.001. Age, sex, goiter grade, triiodothyronine, thyrotropin, and thyrotropin receptor antibodies were significant predictors of recurrence in both "conventional" and "long-term" groups but free thyroxine just in the "long-term" group. The risk-scoring model had a good discrimination power (optimism corrected c-index = 0.78,95%CI = 0.73-0.82) with a range of 0-14 and sensitivity of 86% and specificity of 62% at the risk-score of eight. CONCLUSION: A relapse-free state was achieved in 83% of patients with Graves' hyperthyroidism 84 months after cessation of long-term methimazole treatment which could be predicted by some significant predictors in a simple risk-scoring system.

Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial.

BACKGROUND: Understanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importance to design therapeutic regimens that are able to simulate normal thyroid hormone secretion while avoiding excursions in the T3 serum concentration. Here, we designed a parallel randomized clinical trial to characterize the PK and PD of the combined preparations of LT4 + SR-T3 in hypothyroid patients. METHODS: Radioiodine-treated hypothyroid patients over 20 years of age, who attained euthyroidism with LT4 monotherapy were recruited from the Endocrine Clinic in Tehran. The patients were allocated to two intervention groups of group A: 9 µg SR-T3 plus 68.5 µg LT4 (ratio 1:7.5) and group B: 12 µg SR-T3 plus 60 µg LT4 (ratio 1:5), and a control group with LT4 monotherapy. For PD study, thyroid hormone profile was evaluated at 8 and 12 weeks intervals after intervention. To assess PK properties of SR-T3, T3-Cmax, T3-Tmax and AUC0 - 24 were calculated at the last visit. RESULTS: Serum T4 and FT4 concentrations decreased in the intervention groups after 3 months. No significant difference was observed in serum T3 and FT3 concentrations before and after intervention. Serum T3/T4 ratio increased significantly in the intervention groups after intervention, with the highest increase in group B from 8.6 ± 2.03 at baseline to 12.2 ± 1.6. Comparison of trial groups at follow-up showed no differences in serum TSH, T4, T3 and T3/T4 concentrations among different groups. During 24 h, minimal variation in serum T3 concentration was observed in group B with mean ∆T3 of 15.4 ± 10.5 ng/dl. T3-Tmax, T3-Cmax and AUC0 - 24 in the combined sustained-release preparation were 4.38 ± 1.1 h., 101.0 ± 5.7 ng/dl and 2257 ± 110 ng.h/L, respectively which were significantly different from the control group. CONCLUSION: Combined treatment with a single dose of SR-T3 plus LT4 is associated with increased serum T3/T4 ratio and minimal excursions in serum T3 concentration during 24 h; however, it was not significantly different from the control group. To incorporate sustained-release T3 in the management of hypothyroidism, a higher ratio of SR-T3 to LT4 than that of the previously recommended by the international organizations is suggested. IRCT REGISTRATION NUMBER: IRCT20100922004794N13. https://www.irct.ir/search/result?query=IRCT20100922004794N13 . Registration date: 08/12/2021.

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine.

OBJECTIVE: The aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism. METHODS: A total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment. RESULTS: The rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up. CONCLUSION: Progression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.

Long-term thionamide antithyroid treatment of Graves' disease.

Thionamide antithyroid drugs (ATD) are the treatment of choice for Graves' hyperthyroidism. The major drawback of ATD treatment for 1-2 years is the relapse of hyperthyroidism in about 50% of patients. Recently, it has been shown that ATD treatment for more than five years is accompanied by long-term remission in majority of patients without additional major side effects in both adults and children. Compared to radioactive iodine therapy, long-term ATD results in more favorable outcomes. This review summarizes the evidence on long-term ATD therapy regarding the remission rate of hyperthyroidism, efficacy and safety, indications and mode of therapy in patients with hyperthyroidism.

Efficacy and Safety of Long-Term Methimazole versus Radioactive Iodine in the Treatment of Toxic Multinodular Goiter.

BACKGRUOUND: This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI). METHODS: In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter. RESULTS: After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group. CONCLUSION: In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

Time to Normalization and Sustainable Normal Serum Thyrotropin Concentrations in Patients with Hyperthyroidism: Comparison of Methimazole and Radioactive Iodine Treatments.

OBJECTIVE: The aim of this study was to compare the "time to euthyroidism" and "time spent in euthyroidism" following methimazole (MMI) and radioactive iodine (RAI) treatments. METHODS: Three hundred fifty-eight patients with hyperthyroidism, 178 who underwent long-term MMI treatment and 180 patients who underwent RAI treatment, were analyzed. The time to normalization of increased serum values of free thyroxine and triiodothyronine and suppressed serum thyroid-stimulating hormone (TSH) values as well as the percentage of time that the thyroid hormone levels remained within normal ranges during a mean follow-up time of 12 years were compared. RESULTS: The mean time to euthyroidism was 4.59 ± 2.63 months (range, 2-16 months) in the MMI group and 15.39 ± 12.11 months (range, 2-61 months) in the RAI group (P < .001). During follow-up, the percentage of time spent in euthyroidism was 94.5% ± 7.3% and 82.5% + 11.0% in the MMI and RAI groups, respectively (P < .001). Serum TSH values above and below the normal range were observed in 5.3% and 0.2% of patients, respectively, in the MMI group and 9.8% and 7.7% of patients, respectively, in the RAI group (P < .001). The time to euthyroidism and the percentage of time spent in euthyroidism in 40 RAI-treated patients with euthyroidism were similar to those in the MMI group and significantly shorter than those in the RAI-treated hypothyroid and relapsed subgroups. In patients who continued MMI therapy for >10 years, the percentage of time spent in euthyroidism was >99%. CONCLUSION: In our cohort of selected patients, MMI therapy was accompanied by faster achievement of the euthyroid state and more sustained normal serum TSH levels during long-term follow-up compared with RAI therapy.

Incidence of Thyroid Dysfunction Facing Metabolic Syndrome: A Prospective Comparative Study with 9 Years of Follow-Up.

BACKGROUND: Studies assessing thyroid hormones in metabolic syndrome (MetS) patients are contradictory. Also, the effect of MetS on thyroid function over time is not yet evaluated. This study investigated the prevalence and incidence of thyroid dysfunction (TD) as well as time trends of thyroid hormones in subjects with and without MetS, during a 10-year follow-up in Tehranian adult population. METHODS: This is a prospective cohort study conducted in the framework of Tehran Thyroid Study on 5,786 subjects aged ≥20 years: 4,905 eligible participants entered the study after excluding those with corticosteroid or radioactive iodine use, pregnancy, thyrotropin (TSH) <0.1 and >10 mU/L, and missing data. Physical examinations were performed and serum concentrations of TSH, free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), fasting plasma glucose, insulin, and lipid profile were assessed at baseline and 3-year intervals during the follow-up. MetS was defined according to the Joint Interim Statement Definition. RESULTS: At baseline, there were no difference in median serum concentrations of FT4 and TSH between MetS and non-MetS group after adjusting for age, sex, BMI, smoking, and TPOAb positivity. Although there was higher risk of overt (42%) and subclinical hypothyroidism (16%) in MetS compared with non-MetS subjects, no significant difference was observed in adjusted ORs for any TD between 2 groups. There were also no significant differences in time trends of TSH, FT4, TPOAb positivity, and incidence rates of TDs between MetS and non-MetS groups during 10 years, after adjustment for age, sex, BMI, smoking status, and TPOAb positivity. CONCLUSION: MetS is not associated with thyroid hypofunction considering other important confounders such as age, sex, smoking, BMI, and TPOAb positivity. There is also no difference in the trend of thyroid hormones and incidence of TD between MetS and non-MetS subjects during a 10-year follow-up.

Long term prognostic implication of newly detected abnormal glucose tolerance among patients with stable cardiovascular disease: a population-based cohort study.

BACKGROUND: Fasting plasma glucose (FPG) and 2-h post challenge plasma glucose (2 h-PCPG), whether as continuous or categorical variables, are associated with incident cardiovascular disease (CVD) and diabetes; however, their role among patients with existing CVD is a matter of debate. We aimed to evaluate associations of different glucose intolerance states with recurrent CVD and incident diabetes among subjects with previous CVD. METHODS: From a prospective population-based cohort, 408 Iranians aged ≥ 30 years, with history of CVD and without known diabetes were included. Associations of impaired fasting glucose (IFG) according to the American Diabetes Association (ADA) and World Health Organization (WHO) criteria, impaired glucose tolerance (IGT), newly diagnosed diabetes (NDM) with outcomes of interest were determined by multivariable Cox proportional hazard models after adjustment for traditional risk factors. Furthermore, FPG and 2 h-PCPG were entered as continuous variables. RESULTS: Over a decade of follow-up, 220 CVD events including 89 hard events (death, myocardial infarction and stroke) occurred. Regarding prediabetes, only IFG-ADA was associated with increased risk of hard CVD [hazard ratio(HR), 95%CI: 1.62,1.03-2.57] in the age-sex adjusted model. In patients with NDM, those with FPG ≥ 7 mmol/L were at higher risk of incident CVD/coronary heart disease(CHD) and their related hard outcomes (HR ranged from 1.89 to 2.84, all P < 0.05). Moreover, those with 2 h-PCPG ≥ 11.1 mmol/L had significant higher risk of CVD (1.46,1.02-2.11), CHD (1.46,1.00-2.15) and hard CHD (1.95:0.99-3.85, P = 0.05). In the fully adjusted model, each 1 SD increase in FPG was associated with 20, 27, 15 and 25% higher risk of CVD, hard CVD, CHD and hard CHD, respectively; moreover each 1 SD higher 2 h-PCPG was associated with 21% and 16% higher risk of CVD, and CHD, respectively. Among individuals free of diabetes at baseline (n = 361), IFG-ADA, IFG-WHO and IGT were significantly associated with incident diabetes (all P < 0.05); significant associations were also found for FPG and 2 h-PCPG as continuous variables (all HRs for 1-SD increase > 2, P < 0.05). CONCLUSIONS: Among subjects with stable CVD, NDM whether as high FPG or 2 h-PCPG, but not pre-diabetes status was significantly associated with CVD/CHD and related hard outcomes.

Association of obesity phenotypes in adolescents and incidence of early adulthood type 2 diabetes mellitus: Tehran lipid and glucose study.

OBJECTIVE: Obesity and metabolic syndrome, which has an increasing prevalence among adolescence, are associated with metabolic abnormalities. This study investigates the role of adolescent obesity phenotypes in predicting the incidence of early adulthood type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Participants were divided into four obesity phenotypes: Metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). Multivariate-adjusted hazard ratios (HRs) were calculated for T2DM incidence. RESULTS: In this cohort study, 2306 Tehranian adolescents with an average age of 15.1 ± 2.4 years were included. The median (IQ 25-75) follow-up was 15.5 (12.8-17.1) years and the median (IQ 25-75) age of participants at the end of follow-up was 30 (26-32) years old. The incidence rate of T2DM during the early adulthood was [1.37 (95% CI: 0.89-2.10)] and [3.18 (95% CI: 2.44-4.16)] per 1000 person per year in boys and girls, respectively. MHO phenotype was not associated with an increased risk of T2DM for both sexes. Adjusted HRs for MUO were [4.30 95% CI (1.48-12.43)] and [3.39 95% CI (1.78-6.45)] in boys and girls, respectively. MUNW phenotype was associated with an increased risk of T2DM only in boys. After adjustment for adulthood BMI, all the phenotypes for both sexes lost their significance, except for boys with MUNW phenotype [HR = 3.46 95% CI (1.15-10.45)]. CONCLUSIONS: Unhealthy obesity phenotypes; in contrast with MHO; had an increased risk of T2DM incidence, apart from girls with MUNW. After adjusting the adulthood BMI, all phenotypes turn insignificant, except for boys with MUNW.

Effects of vitamin K2 supplementation on atherogenic status of individuals with type 2 diabetes: a randomized controlled trial.

BACKGROUND: This study was aimed to examine the effects of vitamin K2 supplementation on atherogenic status, assessed by insulin resistance (IR)-related indexes, in patients with type 2 diabetes mellitus (T2DM). METHODS: In this double-blind, controlled trial, 68 patients with T2DM on the oral glucose-lowering medications were randomly allocated into two groups receiving daily intakes of 360 µg MK-7 or placebo for 12 weeks. Eight different IR-related indexes were calculated at the baseline and end of the trial. RESULTS: At the end of the study, atherogenic coefficient (mean ± SD: - 0.21 ± 0.45 vs. 0.02 ± 0.43; p = 0.043), triglyceride-glucose index (8.88 ± 0.55 vs. 9.23 ± 0.69; p = 0.029), and atherogenic index of plasma (0.37 ± 0.27 vs. 0.51 ± 0.24; p = 0.031) were significantly lower in the vitamin K2 group, compared to the placebo. However, after accounting for their baseline values, the differences were no more significant. No significant differences were observed in Castelli's Ӏ and ӀӀ risk indexes, the ratio of triglycerides to high-density lipoprotein cholesterol, lipoprotein combine index, and the metabolic score for insulin resistance index between the two groups at the end of the study. CONCLUSIONS: Daily intakes of 360 µg vitamin K2 in the form of MK-7 for 12 weeks could not improve the IR-related indexes of Cardiovascular Diseases risk. TRIAL REGISTRATION: The trial was registered on Iranian Registry of Clinical Trials registry (Trial ID. IRCT20190824044592N1) on 22 December 2019. The record can be found at https://en.irct.ir/trial/41728 .

Iranian Endocrine Society Guidelines for Screening, Diagnosis, and Management of Gestational Diabetes Mellitus.

CONTEXT: Gestational diabetes mellitus (GDM) is an important endocrine disorder in perinatology, associated with several maternal and neonatal complications. Development of national guidelines can inform clinicians, health policymakers, and researchers about the most recent evidence and practical issues of diagnosis and management of GDM. OBJECTIVES: We aimed to develop clinical practice guidelines for the diagnosis and management of GDM in Iranian pregnant women. EVIDENCE ACQUISITION: The Iranian Endocrine Society constituted a task force, consisting of obstetrician-gynecologists, endocrinologists, a clinical nutritionist, a clinical epidemiologist, and a librarian, to review the published literature and propose national guidelines for the diagnosis and management of GDM. The consensus was reached on all recommendations in several group meetings with a majority decision. The evidence and recommendations were graded according to the American College of Physicians' Guideline Grading System. RESULTS: The proposed guidelines included recommendations for screening, diagnosis, and management of GDM in Iran. CONCLUSIONS: By using an evidence-based approach, these national GDM guidelines can address important clinical issues in the diagnosis and management of Iranian women with GDM.

Efficacy of low-dose methimazole in control of multiple relapses of Graves' hyperthyroidism: a case report.

INTRODUCTION: Methimazole (MMI) is the treatment of choice for patients with Graves' disease. The major drawback of this treatment is the relapse of hyperthyroidism in half of the patients after discontinuation of the recommended conventional 12-18 months of MMI treatment. TSH receptor antibody (TRAb) concentration is recognized as the strongest predictor of hyperthyroidism relapse. In this case report, efficacy of low-dose MMI to control hyperthyroidism even after multiple recurrences in the setting of normal TRAb concentrations is shown. CASE PRESENTATION: An 80-year-old Iranian woman with Graves' disease was treated with MMI for 31 years. While receiving treatment, she always had a normal serum TRAb concentration; however, three times during the 31 years she decided to stop MMI therapy, and each time the disease recurred 16-21 months after MMI withdrawal. It is noteworthy that she maintained euthyroidism with the low-dose 1.25-2.5 mg MMI daily without any adverse events during three decades of treatment. CONCLUSIONS: Normal serum TRAb is not a sufficiently strong marker to predict relapse of Graves' hyperthyroidism. Long-term therapy with low-dose MMI is an effective and safe treatment to sustain euthyroidism.

Cumulative Effects of Thyroid Hormones Over 10 Years and Risk of General and Abdominal Obesity.

We aimed to assess if changes in thyrotropin (TSH) and free thyroxine (FT4) over 10 years of follow-up would be associated with changes in body mass index (BMI) and waist circumference (WC) or risk of obesity. We enrolled 2317 out of 4179 participants in Tehran Thyroid Study with serum TSH between 0.1-10 mU/l and without history of thyroid medication or surgery. Serum concentrations of FT4 and TSH were measured at baseline and three follow-ups (1999-2011). To account for within-subject correlation, the generalized estimating equation was used to assess the association between one standard deviation(SD) change in the main exposures [cumulative excess (CE)TSH and CEFT4] and changes in BMI and WC; calculated scores of CETSH and CEFT4 were included in models as time-varying exposures. Cumulative excess of TSH or FT4 was not associated with increased incidence of general or abdominal obesity. However, CEFT4 was negatively associated with BMI only in overweight and obese subjects. In GEE analysis, one unit increase in TSH was associated with 0.02 kg/m2 increase in BMI (95% CI: 0.01, 0.03), which remained significant only in women; although the association was not significant after adding FT4 to model. One unit increase in FT4 was associated with 1.5 kg/m2 decrease in BMI (95% CI:-1.8,-1.2) and 4.1 cm decrease in WC (95% CI:-5.1,-3.1) in both sexes independent of TSH and other confounders. Cumulative excess of TSH or FT4 indicated no risk for general or abdominal obesity. However, FT4 was negatively associated with BMI and WC independent of TSH.

Impact of short- and long-term exposure to air pollution on blood pressure: A two-decade population-based study in Tehran.

Plenty of recent studies on the impact of air pollution on blood pressure (BP) exist; however, there is a lack of data for the highly polluted Eastern Mediterranean region. We evaluated the associations of short-term exposure to air pollutants with systolic BP (SBP) and diastolic BP (DBP) and the long-term impact of air pollutants on incident hypertension, among Tehranian adults. In the Tehran Lipid and Glucose Study, 4580 nonhypertensive participants aged 20-69 years (41.6% male) were followed from 2001 to 2018 through 3-year follow-ups and 4-5 examinations of them were recorded. The air pollutants included particulate matter with a diameter ≤10 µm (PM10), carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2). The mixed-effects transition model estimated the air pollution impact on BP. The proportional hazards Weibull model measured the long-term effects of air pollutants on the multivariate hazard of incident hypertension. The air pollutants were put in the models in the form of mean annual level, applying three versions of 1, 2, and 3 years before the follow-ups. During a median follow-up of 12.3 years, 1618 cases of hypertension were found. In the short-term, increase in CO did not affect SBP but decreased DBP with a delay effect lasting for 14 days; increase in NO2 raised SBP with a 14-day lag, however did not change DBP; increase in O3 reduced SBP with a 14-day lag but made slight non-significant increase in DBP; rise in PM10 concentrations led to increased SBP (lag 0-3 days) and DBP with lags of 0-3 days and 12-14 days and increase in SO2 made the largest increases in DBP with lags lasting for 14 days, but did not affect SBP. Regarding incident hypertension in the long-term, the increase in CO had no significant effect; increase in NO2 decreased the risk over the 2- and 3-year time spans; rise in O3, PM10, and SO2 levels increased the risk in all time spans; the largest hazard ratio [1.96 (95% CI: 1.48, 2.62)] for incident hypertension was attributable to PM10 in 3 years. Considering the major effects of air pollutants including O3, SO2, and especially PM10 on incident hypertension, urgent public health policies should be implemented to reduce the burden of air pollution in metropolitan city of Tehran.

Control of Graves' hyperthyroidism with very long-term methimazole treatment: a clinical trial.

BACKGROUND: Long-term antithyroid drug therapy has become one of the options for treatment of Graves' hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years. METHODS: Fifty nine patients with Graves' disease on long-term MMI for 14.2 ± 2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years. RESULTS: Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8 ± 1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study. CONCLUSIONS: Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves' hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research. TRIAL REGISTRATION: IRCT201009224794N1, 2010-10-25. Retrospectively registered. https://www.irct.ir/trial/5143 .

Determination of age and sex specific TSH and FT4 reference limits in overweight and obese individuals in an iodine-replete region: Tehran Thyroid Study (TTS).

Introduction: To determine age and sex-specific thyrotropin (TSH) and free thyroxine (FT4) reference ranges according to body mass index (BMI) categories. Methods: With regards to the National Academy of Clinical Biochemistry (NACB) criteria, a total of 2818 individuals from the Tehran Thyroid Study population was selected and categorized in three BMI groups. Results: TSH levels did not differ significantly between BMI groups (p = .054). Females had statistically higher TSH levels than males in all BMI categories (p < .001). According to age-specific analyses, the youngest category (20-29 years) had the highest median values of serum TSH in all BMI groups. With increasing BMI, the 2.5th percentile of TSH remained approximately unchanged and the 97.5th percentile showed an increasing pattern. FT4 level was significantly higher in the normal weight group compared to obese individuals (p < .001); females had significantly lower FT4 levels than males in normal weight and obese groups (p < .001). According to age categories, the youngest group (20-29 years) had higher levels of FT4 than the elderly group in all BMI categories. A decreasing pattern in both 2.5th and 97.5th percentiles of FT4 was observed along with increasing BMI. Conclusions: Compared to the normal weight population, obese individuals have slightly lower FT4 concentrations accompanied by similar TSH levels. With increasing BMI, upper limits of TSH and FT4 show increasing and decreasing patterns, respectively.

Treatment of Subclinical Hyperthyroidism in the Elderly: Comparison of Radioiodine and Long-Term Methimazole Treatment.

Background: This study aimed to compare the effectiveness and safety of radioiodine (RAI) and long-term methimazole (MMI) in the treatment of subclinical hyperthyroidism (SH) in the elderly. Methods: From 306 patients, aged ≥65 years, with SH, 83 patients with thyrotropin <0.1 mU/L entered the study. In this randomized parallel-group trial, 41 and 42 patients were randomized to either RAI or long-term MMI treatment, respectively. Results: In the RAI and MMI groups, 3 and 4 patients were excluded due to side effects, choosing other modes of treatment, and not returning for follow-up; 35 and 36 patients completed 60 months of follow-up, respectively. In the RAI group, 23 (66%) became hypothyroid, and 12 (34%) remained euthyroid 60 months after a fixed dose of 15 mCi RAI. In the MMI group, the starting dose was 10 mg daily and decreased to 4.9 ± 1.0, 4.3 ± 1.0, 4.4 ± 1.4, 4.3 ± 1.8, and 3.7 ± 1.3 mg after 1, 2, 3, 4, and 5 years of continuous MMI treatment, employing titration method. By the end of study, 34 (94%) patients were euthyroid and 2 patients with diffuse goiter developed spontaneous hypothyroidism with MMI treatment. Minor adverse events occurred in both groups in the first four months of treatment. No death or serious side effects were observed during 60 months of follow-up. Conclusions: Both RAI and long-term low-dose MMI therapies are effective and safe for treatment of SH in the elderly.

Correction To: Sex-Specific Incidence Rates and Risk Factors for Hypertension During 13 Years of Follow-up: The Tehran Lipid and Glucose Study.

[This corrects the article DOI: 10.5334/gh.780.].