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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: To investigate future diabetes in different abdominal obesity phenotypes during 12 years of follow-up.Methods: For this population-based cohort, 7982 adults without diabetes including 3533 men and 4449 women, aged ≥20 years were selected from the Tehran Lipid and Glucose Study. Abdominal obesity was defined according to the national cutoffs for waist circumference (WC). Metabolic health was defined as having ≤1 metabolic abnormality based on Joint Interim Statement (JIS) criteria other than WC. Participants were classified into 4 groups of abdominal obesity phenotypes: Metabolically healthy non-abdominal obese (MHNAO), metabolically healthy abdominal obese (MHAO), metabolically unhealthy non-abdominal Obese (MUNAO), and metabolically unhealthy abdominal obese (MUAO).Results: In total, 1018 cases of incident diabetes occurred. Compared to the MHNAO phenotype, based on multivariate Cox regression models, diabetes risk was increased in all unhealthy phenotypes except the MUNAO phenotype in men. Regarding the association of the MHAO phenotype with incident diabetes, borderline statistical significance in men [HR 1.5 (95% CI: 1.0-2.36), p-value: 0.07] and statistical significance in women [HR 1.68 (95% CI: 1.08-2.6)] were detected.Conclusions: In addition to unhealthy phenotypes except the MUNAO phenotype in men, the MHAO phenotype is also associated with incident diabetes, highlighting the importance of preventive strategies in this subgroup of abdominally obese subjects. [ABSTRACT FROM AUTHOR]

Longitudinal studies considering associations between thyroid function in the reference range (RR) with blood pressure (BP) are scarce and contradictory. We aimed to investigate the associations of serum thyrotropin (TSH) and free T4 (FT4) with different components of BP also incident prehyperetension (preHTN) and HTN during a 9-year follow-up. A sum of 2282 euthyroid individuals from an ongoing population-based cohort study were selected. A sex-stratified multivariate generalized estimating equation (GEE) method was employed. Moreover, a multivariate transitional model was used considering preceding BP status as a predictor of dichotomous outcomes of preHTN and HTN. Multivariate-adjusted GEE analysis revealed a decreasing trend for systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP) throughout the study period in both men and women, either adjusted for serum TSH or FT4 levels. Serum FT4 within the RR was positively associated with all BP parameters in total population and in men, but serum TSH had a statistically significant mild increasing effect only on SBP, DBP and MAP of men. Multivariate transitional model found no association between serum TSH levels within the reference range (RR) and BP status; regarding serum FT4, a 1 ng/dl higher FT4 was associated with 40 % increased risk of preHTN [OR (95 % CI), 1.40 (1.02-1.90)], but not with HTN [OR (95 % CI), 0.93 (0.80-1.09)]. It is concluded that serum FT4 within the RR is more strongly associated with BP parameters compared to TSH. This association is not consistent between men and women. Moreover, higher FT4 is associated with increased risk of preHTN. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to evaluate the association between change in thyroid function tests within the euthyroid range and body mass index (BMI) in persons with normal weight at baseline. Methods: This study investigated 1,100 normal-weight euthyroid persons in a population-based cohort study, Tehran Thyroid Study. BMI was calculated and serum concentrations of thyrotropin (TSH) and free T4 (FT4) were assayed at baseline and after 10 years of follow-up. We evaluated the relationship between thyroid and obesity based on 2 definitions for outcome: (1) a binary outcome as BMI <25 or ≥ 25 kg/m2, and (2) a multinomial outcome as normal BMI, overweight, and obese. Results: A total of 569 women and 531 men, aged 36.3 ± 13.5 years, were included. Modified Poisson regression analysis for binary outcome, after adjustment for age, sex, smoking, and antithyroid peroxidase antibody status, revealed a negative association between delta serum FT4 and follow-up BMI (relative risk 0.55 [95% CI 0.37–0.80]) without any significant association between change in serum TSH and follow-up BMI. However, in multinomial logistic regression analysis, we found no relationship between delta serum FT4 or TSH and follow-up BMI categories, for either overweight or obese vs. normal-weight participants. Conclusions: In normal-weight euthyroid individuals, changes in serum concentrations of FT4, but not TSH, may contribute to change in body weight. [ABSTRACT FROM AUTHOR]

Background and aims Considering the inconsistent data available on cardiovascular (CV) risk of different obesity phenotypes, the aim of this study was to investigate the development of cardiovascular disease (CVD) in different obesity phenotypes over a median follow-up of 12 years. Methods In this large population-based cohort, 7842 participants (44.8% men), aged ≥ 30 years, were enrolled. Participants were divided into six phenotypes based on body mass index and metabolic status. Metabolic health was defined based on two definitions: 1) having ≤1 component of metabolic syndrome using the Joint Interim Statement (JIS) criteria and 2) homeostasis model assessment-insulin resistance (HOMA-IR) < 2.6 mole × μU/L 2 . Multivariate adjusted hazard ratios (HRs) were calculated for cardiovascular events. Results A total of 712 new CVD events occurred. CV risk increased in all metabolically unhealthy phenotypes. Multivariable adjusted HRs for CVD events in metabolically healthy overweight (MHOW) and metabolically healthy obese (MHO) participants were 1.22 (0.73–2.04) and 1.74 (0.68–4.44), respectively. CV risk increased in all obesity phenotypes based on insulin resistance except the insulin resistance-normal weight group. However, this increased risk disappeared after further adjustment for metabolic risk factors. Conclusions Our findings showed that CV risk did not increase in MHOW and MHO phenotypes over a 12-year follow-up. However, all metabolically unhealthy phenotypes were associated with increased incident CVD. Further studies with longer follow-up are needed to confirm the benign nature of MHOW/MHO phenotypes. [ABSTRACT FROM AUTHOR]

Background: Data regarding the impact of different lipid measures on cardiovascular diseases (CVD) and mortality events is not consistent. We aimed to evaluate the relationship between different lipid parameters and incident CVD and mortality events in an Iranian population over a median follow-up of 11.9 years. Methods: The study was conducted on 2532 men and 2986 women aged ≥ 40 years. Multivariate adjusted hazard ratios (HRs), using age as time scale, were calculated for every 1 standard deviation (SD) increase in total cholesterol (TC), logarithm-transformed triglycerides (ln-TGs), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), non-HDL-C, TC/HDL-C and ln-TGs/HDL-C. Covariates included gender (female as reference), body mass index, education status, low physical activity, smoking, blood pressure status (normotension, prehypertension and hypertension), glucose tolerance status (normal glucose tolerance, prediabetes and diabetes) and lipid lowering drugs. The same analyses were also repeated for tertiles of all lipid measures. Considering the absence of interaction between gender and lipid parameters, we used a sex-adjusted analysis. For analyses of mortality events, prevalent CVD was adjusted as well (All p for interactions > 0.1). Results: A total of 789 new CVD events, 279 cardiovascular (CV) and 270 non-CV deaths occurred. In multivariate analysis, all lipid measures except HDL-C showed significant risk for new CVD events with HRs ranged from 1.14 to 1.27 for ln-TGs/HDL-C and LDL-C, respectively (all p-values ≤ 0.001). Considering CV mortality, there were significant positive associations between TC, LDL-C, non-HDL-C, TC/HDL-C and CV mortality events in sex-adjusted analysis; however after multivariate analysis, these associations attenuated and reached to null. Applying lipid measures as categorical variables, only TC displayed a positive association with CV mortality in multivariate analysis [TC ≥ 6.14 mmol/L: HR 1.43 (1.04-1.98)]. In multivariate analysis, there were negative significant associations between all lipid measures except HDL-C and non-CV mortality; every 1-SD increase in TC, LDL-C, non-HDL-C, ln-TGs,TC/HDL-C and ln-TGs/HDL-C was associated with 24, 25, 27, 19, 23 and 17 % decreased risk in non-CV mortality (all p-values ≤ 0.01). Conclusions: These findings indicate divergent associations of TC, LDL-C, non-HDL-C, TC/HDL-C, TGs and TGs/HDL-C with CVD vs non-CV mortality, demonstrating a higher risk for the former and lower risk for the latter. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have shown interindividual variation in free thyroxine (FT4) serum levels and thyroid stimulating hormone (TSH) in healthy persons. Genetic factors mainly determine this variation, and genome-wide association studies have increased the number of thyroid function-associated variants. The present study investigates the association of candidate variants with FT4 and TSH in a euthyroid Iranian population. Method: A total of 2931 unrelated euthyroid subjects (FT4 10.29–21.88 pmol/L; TSH 0.32–10 mIU/L, thyroid peroxidase antibody TPOAb < 33 IU/mL in men and < 35 IU/mL in women), with available genotypes were chosen from the Tehran Thyroid Study (TTS), to examine the impact of selected SNPs on thyroid hormone under the additive genetic model. In order to evaluate regional associations with FT4 and TSH levels, a haplotype analysis was done. Results: We identified a strong association between the rs4338740-C allele and TSH in the adjusted model (β = -0.095, P-value = 0.0004). Also, findings indicated that rs4954192 ACMSD and rs4445669 CADM1 correlated with normal TSH levels (P-value = 0.011, P-value = 0.014, respectively). Haplotype analysis revealed that two haplotypes were significantly associated with TSH levels in euthyroid individuals. The ACGA and AC haplotypes on chromosomes 8 and 14 were significantly correlated with normal TSH levels, respectively (P-value = 0.014, P-value = 0.016). Conclusions: This is the first genetic association study with TSH and FT4 reference values in an Iranian population. Our findings indicate that a few gene variants associated with the reference values of TSH in other populations are also associated with the reference values of TSH in Iranians. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The association between obesity and autoimmune diseases has been suggested by several previous studies. The objective of our study was to assess the association of abdominal obesity phenotypes with thyroid autoimmunity. This study was conducted within the framework of a population-based cohort study, Tehran Thyroid Study (TTS) on 4708 subjects without thyroid autoimmunity at baseline. Participants were categorized into four abdominal obesity phenotypes according to waist circumference (WC) and other metabolic syndrome components. Serum concentrations of thyroid peroxidase antibody (TPOAb), free T4 (FT4), thyrotropin (TSH), glucose, and lipid profiles were measured after 3, 6 and 9 years of follow-up. Cox proportional hazard models were used to evaluate associations of different phenotypes with the incidence of thyroid autoimmunity, adjusted for age, sex, FT4, and TSH. Highest and lowest incidence rates of TPOAb positivity were observed among metabolically unhealthy, non-abdominally obese (MUNAO) [8.78 (7.31–10.55) per 1000 person-years of follow-up] and metabolically unhealthy abdominally obese (MUAO) [4.98 (3.88–6.41) per 1000 person-years of follow-up] phenotypes. Considering the metabolically healthy non-abdominal obese (MHNAO) individuals as reference, none of metabolically healthy abdominally obese (MHAO), MUNAO, and MUAO phenotypes were associated with increased risk of developing TPOAb positivity. Compared to individuals with high WC, the incidence rate (95%CI) of TPOAb positivity was higher among those with normal WC: 8.44 (7.13–10.0) vs 5.11 (4.01–6.51) per 1000 person-years, respectively. Higher WC was not associated with incident TPOAb positivity. There was no significant association between baseline abdominal obesity phenotype status and development of TPOAb positivity over 9 years of follow-up. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The authors discuss the classification and diagnosis of diabetes in American Diabetes Association standards of medical care in diabetes. Topics mentioned include the overall prevalence of metabolically obese but normal weight individuals, weight of different diabetes risk factors for predicting diabetes, and risk factors for prediction of diabetes in different ethnicities.

Background: Considering inconsistent and conflicting data on associations of thyroid function, within the reference range, with anthropometric measures and metabolic syndrome, this study aimed to investigate the relationship between thyroid function and different obesity phenotypes over nine years of follow-up. Methods: This study was conducted on 1938 individuals from an ongoing population-based cohort study, the Tehran Thyroid Study. Participants were categorized into four obesity phenotypes based on body mass index and metabolic status. To investigate the associations of thyrotropin and free thyroxine (fT4) with incidence of different obesity phenotypes across the study period, a multivariate approach based on a generalized estimating equation method was used. Results: At baseline, individuals with the metabolically healthy normal weight (MHNW) phenotype had higher serum fT4 levels (1.2 ± 0.16 ng/dL vs. 1.14 ± 0.14 ng/dL, 1.16 ± 0.14 ng/dL, and 1.17 ± 0.15 ng/dL in metabolically healthy obese [MHO], metabolically unhealthy normal weight, and metabolically unhealthy obese individuals, respectively). The results of the generalized estimating equation analysis after multivariate adjustment for age, sex, smoking, physical activity, education level, thyroid peroxidase antibody status, and homeostasis model assessment-insulin resistance showed that each 1 ng/dL increment in fT4 levels within the reference range was accompanied with a 1.65-fold [confidence interval (CI) 1.09–2.5] increase of developing the MHNW phenotype during 9.2 years of follow-up. Moreover, each 1.0 ng/dL increment in fT4 within the reference range was associated with a 50% decreased risk of developing the MHO phenotype (odds ratio = 0.50 [CI 0.32–0.76]). Meanwhile, a significant positive association was found between serum thyrotropin levels and development of the metabolically unhealthy normal weight phenotype (odds ratio = 1.22 [CI 1.01–1.48]). Conclusions: Serum fT4 concentrations within the reference range are associated with the development of some obesity phenotypes, including the MHNW and MHO phenotypes, after consideration of potential confounders. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

Objective: Prehypertension is associated with cardiovascular disease (CVD). There is no study to examine the incidence and risk factors of prehypertension in a sex stratified setting. The aim of this study was to examine the effect modification of sex for different risk factors which predicts the progression from normotension to prehypertension in a Middle East population-based cohort, during a median follow-up of 9.2 years. Methods: A multivariate Cox analysis was performed among 1466 and 2131 Iranian men and women, respectively, who were free of prehypertension, hypertension, CVD and diabetes at baseline and free of incident hypertension without preceding prehypertension at follow-up. Incident prehypertension at follow-up was defined as systolic blood pressure (SBP) of 120–139 mmHg and/or diastolic blood pressure (DBP) of 80–89 mmHg. Results: Overall, 1440 new cases of prehypertension were identified resulting in an incidence rate of 593/10000 person-years; the corresponding values for women and men were 489/10000 and 764/10000person-years, respectively. There were significant interactions between gender with age, DBP, waist-to-hip-ratio (WHpR) and estimated glomerular filtration rate (eGFR) (all P-values <0.05) in multivariate analysis. Strong associations were found between age, body mass index (BMI) and SBP with incident prehypertension in both genders. However, the effect of DBP and WHpR was significant among women and 2-hour post challenge plasma glucose (2h-PCPG)was an independent risk factor for men. In the sex-adjusted analysis, glomerular hyperfiltration [Hazard ratio (HR) and 95%CI: 1.01 (1.00–1.01), P-value = 0.02], age, BMI, WHpR, SBP and DBP had higher risks while being female [HR (95%CI): 0.81(0.69–0.94), P-value = 0.01] had a lower risk for incident prehypertension. Conclusion: According to this study results, among Iranian population with high incidence of prehypertension, general adiposity and glomerular hyperfiltration in total, 2h-PCPG in men and central adiposity in women should be emphasized as risk factors for prehypertension. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia (MEN) type 2A, a dominant inherited syndrome caused by germline activating mutations in the RET protooncogene, is characterized by association of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. There is limited data on this disease in the Middle East region. In this paper, we present clinical and genetic studies of an Iranian patient and her family members. The patient was a 49-year old Iranian woman who presented with hypertension due to bilateral pheochromocytoma. She had history of a medullary carcinoma of thyroid which had been operated 28 years ago. Analysis of the RET gene in the family revealed a C634R mutation in codon 11 and 3 polymorphisms, G691S, S836S and S904S in codons 11, 14 and 15, respectively, that might have been important in modifying the clinical picture. Due to paucity of information on MEN type 2 in the area, this study can be helpful in portraying the clinical and cytogenetic characteristics of the disease in the region. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia (MEN) type 2A, a dominant inherited syndrome caused by germline activating mutations in the RET protooncogene, is characterized by association of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. There is limited data on this disease in the Middle East region. In this paper, we present clinical and genetic studies of an Iranian patient and her family members. The patient was a 49-year old Iranian woman who presented with hypertension due to bilateral pheochromocytoma. She had history of a medullary carcinoma of thyroid which had been operated 28 years ago. Analysis of the RET gene in the family revealed a C634R mutation in codon 11 and 3 polymorphisms, G691S, S836S and S904S in codons 11, 14 and 15, respectively, that might have been important in modifying the clinical picture. Due to paucity of information on MEN type 2 in the area, this study can be helpful in portraying the clinical and cytogenetic characteristics of the disease in the region. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To examine the impact of changes in all lipid measures including total cholesterol (TC), log-transformed triglycerides (Ln-TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL-C, TC/HDL-C and Ln TG/HDL-C, over an approximate 3 year duration, on incident type 2 diabetes (T2DM). Methods: A total of 5474 participants, mean age 41.3 years, without prevalent diabetes at baseline or the first follow-up were entered into the study. The association of lipid changes between baseline and the first follow-up i.e., between 1999–2002 and 2002–2005 for those entered in the first phase (n = 4406) and between 2002–2005 and 2005–2008 for participants recruited in the second phase (n = 1068) with incident T2DM over the follow-up period was assessed, using multivariate Cox proportional hazard analysis. Results: During a median follow-up of 8.9 years after the second lipid measurements, 577 incident cases of T2DM occurred. After adjustment for a wide variety of confounders and body mass index (BMI) change, each 1-SD increase in TC, Ln-TG, HDL-C, LDL-C, non-HDL-C, Ln-TG/HDL-C and TC/HDL-C was associated with 12, 14, 0.86, 12, 16, 15 and 13% risk for T2DM, respectively (all p-values < 0.05). However, after further adjustment for fasting plasma glucose (FPG) change, the risk disappeared for all lipid measures, excluding HDL-C [hazard ratio (HR): 0.84 (0.76–0.93)], Ln-TG/HDL-C [1.14 (1.04–1.25)] and TC/HDL-C [1.12 (1.04–1.21)]. Conclusions: Three year changes in all lipid parameters, after adjustment for known risk factors of T2DM and BMI changes, were associated with incident T2DM. The independent risk of HDL-C and its ratios remained even after adjustment for FPG changes. [ABSTRACT FROM AUTHOR]

The article discusses the study that estimates the prevalence of coeliac disease (CD) in Iranian psoriatic patients. It indicates that a positive history of psoriasis was present in the first-degree relatives of 16.2% of patients, but none of them had a family history of CD. It found no association between psoriasis and CD, and a gluten-free diet (GFD) in patients affected by both diseases had no effect on the skin lesions.