Ladan Mehran
@endocrine.ac.ir
Shahid Beheshti University of Medical Sciences,
Research Institute for Endocrine Science
EDUCATION
MD,PhD
RESEARCH INTERESTS
Epidemiology, thyroid, iodine deficiency, metabolic syndrome
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Nazanin Moslehi, Saba Mohammadpour, Parvin Mirmiran, Ladan Mehran, and Fereidoun Azizi
Springer Science and Business Media LLC
Abstract Background Little is known about the association of dietary patterns with thyroid function. Since thyroid function and cardiometabolic variables are inter-related, we investigated whether cardiometabolic-related dietary patterns are associated with thyroid function. Methods This cross-sectional study included 3520 Tehran Lipid and Glucose Study participants. Reduced rank regression was used to find dietary patterns with body mass index, serum fasting glucose, triglycerides, HDL-C, and systolic and diastolic blood pressures as response variables. Two patterns were retained, one based on 35 food groups (native-based pattern) and the other based on the European Prospective Investigation into Cancer and Nutrition Germany (EPIC) food grouping (n = 33). A confirmatory cardio-metabolic dietary pattern was also created according to the weight of food groups proposed by the Framingham Offspring Study (FOS). The association of each pattern with thyroid-stimulating hormone (TSH), free thyroxine, and thyroid peroxidase antibody (TPOAb) and the odds of thyroid dysfunction was examined by linear and logistic regression, respectively. Results The two exploratory dietary patterns were highly correlated and associated with greater TSH levels in euthyroid participants. The adjusted odds ratio (95% CI) of subclinical hypothyroidism per one standard deviation was 1.14 (1.01, 1.28) for the native-based pattern and 1.16 (1.03, 1.31) for the EPIC-based pattern. The odds of subclinical hypothyroidism was significantly greater in the second and third tertiles of the native-based pattern compared to the first tertile in the adjusted model (p-trend = 0.005). The odds of subclinical hypothyroidism increased across the tertiles of the EPIC-based pattern, but the odds was significantly higher only in tertile 3 compared to tertile 1, with an OR (95% CI) of 1.44 (1.07, 1.94) in the adjusted model. The adjusted odds of clinical hypothyroidism were greater in tertile 3 of the native-based pattern compared with tertile 1 (OR = 1.65, 95% CI 1.04, 2.62). The patterns were unrelated to hyperthyroidism or TPOAb positivity. The FOS-based confirmatory score was unrelated to thyroid function. Conclusions A diet high in fast foods, soft drinks, and legumes and low in confectionery, potatoes, butter, and jam and honey was associated with higher TSH levels in euthyroidism and higher odds of subclinical hypothyroidism.
Alireza Amirabadizadeh, Atieh Amouzegar, Ladan Mehran, and Fereidoun Azizi
Springer Science and Business Media LLC
AbstractType 2 diabetes and thyroid function disorders are two common chronic endocrine disorders with the high prevalence in various populations. Metformin is well established as the first-line drug therapy for managing diabetes mellitus. In this meta-analysis, we aimed to determine the effect of metformin on serum TSH and FT4 concentrations in patients with type 2 diabetes. We searched PubMed, Scopus, web of science, Cochrane library, and google scholar to collect information on the effect of metformin on serum TSH and FT4 levels. Demographic and clinical information and serum TSH and FT4 concentrations before and after metformin treatment were extracted. Studies on patients over 18 years of age were included. A total of 11 studies including 1147 patients were selected for the final analysis. In hypothyroid patients, the TSH level decreased significantly after treatment with metformin (Hedges’s g:1.55, 95%CI 0.93–2.16, p-value < 0.001); FT4 level increased slightly after taking metformin, but the increase was not significant (Heddges’s g: − 0.30, 95%CI − 0.90,0.31, p-value = 0.34). In euthyroid subjects, the slight decrease found in TSH and FT4 concentrations was not statistically significant. Metformin reduces TSH levels in hypothyroid patients; however, it has no effect on TSH levels in euthyroid patients. Metformin does not affect serum FT4 levels in euthyroid and hypothyroid patients.
Atieh Amouzegar, Mohammadjavad Honarvar, Safdar Masoumi, Davood Khalili, Fereidoun Azizi, and Ladan Mehran
Springer Science and Business Media LLC
Abstract Background The available evidence indicates that the severity of metabolic syndrome tends to worsen progressively over time. We assessed the trajectory of age and sex-specific continuous MetS severity score (cMetS-S) and its association with the development of diabetes during an 18-year follow-up. Methods In a prospective population-based Tehran Lipid and Glucose Study, 3931 eligible participants free of diabetes, aged 20–60 years, were followed at three-year intervals. We examined the trajectories of cMetS-S over nine years using latent growth mixture modeling (LGMM) and subsequent risks of incident diabetes eight years later. The prospective association of identified trajectories with diabetes was examined using the Cox proportional hazard model adjusting for age, sex, education, and family history of diabetes, physical activity, obesity (BMI ≥ 30 kg/m2), antihypertensive and lipid-lowering medication, and baseline fasting plasma glucose in a stepwise manner. Results Among 3931 participants, three cMetS-S trajectory groups of low (24.1%), medium (46.8%), and high (29.1%) were identified during the exposure period. Participants in the medium and high cMetS-S trajectory classes had HRs of 2.44 (95% CI: 1.56–3.81) and 6.81 (95% CI: 4.07–10.01) for future diabetes in fully adjusted models, respectively. Normoglycemic individuals within the high cMetS-S class had an over seven-fold increased risk of diabetes (HR: 7.12; 95% CI: 6.05–12.52). Conclusion Although most adults exhibit an unhealthy metabolic score, its severity usually remains stable throughout adulthood over ten years of follow-up. The severity score of metabolic syndrome has the potential to be utilized as a comprehensive and easily measurable indicator of cardiometabolic dysfunction. It can be employed in clinical settings to detect and track individuals at a heightened risk of developing T2DM, even if their glucose levels are normal.
Mohammadjavad Honarvar, Ladan Mehran, Safdar Masoumi, Sadaf Agahi, Shayesteh Khalili, Fereidoun Azizi, and Atieh Amouzegar
Springer Science and Business Media LLC
AbstractTraditional metabolic syndrome (MetS) criteria have several limitations, which hinder its use in clinical practice. To overcome the limitations, we investigated the association between age- and sex-specific continuous MetS severity score (cMetS-S) and cardiovascular disease (CVD) and mortality beyond MetS components in the framework of the Tehran Lipid and Glucose Study. Participants aged 20–60 years at baseline were included in the study. We excluded participants with CVD, cancer, use of corticosteroids, estimated glomerular filtration rate < 30 ml/min/1.73 m2, and those who were pregnant. We evaluated the association between cMetS-S with CVD and mortality over 18 years of follow-up among 8500 participants with continuous and quantile approaches using the Cox proportional hazard regression model. In addition, the model performance of cMetS-S for predicting CVD events was compared to the conventional MetS criteria. Participants with higher cMetS-S had a significantly increased risk for CVD, coronary (CHD) and non-coronary heart disease (non-CHD), and all-cause, cardiovascular, and sudden cardiac death. Independent of the confounders and MetS components, the cMetS-S had the HRs of 1.67 (95% CI 1.47–1.89), 1.60 (95% CI 1.37–1.86), and 1.88 (95% CI 1.50, 2.35) for CVD, CHD, and non-CHD events upon 1-SD increment, respectively. The risk of mortality was increased for 1-SD of cMetS-S (all-cause mortality, HR 1.24; 95% CI 1.09–1.41; CVD mortality, HR 1.72; 95% CI 1.20–2.45; sudden cardiac death, HR 1.60; 95% CI 1.03–2.49). The model fitness of cMetS-S was superior to the conventional MetS criteria in predicting CVD and mortality. The cMetS-S provided an additional risk for CVD and mortality beyond the individual MetS components. Standardized cMetS-S could be a potential universal measure to define MetS severity while considering the weighted contribution of MetS components and their variations by age, sex, and ethnicity.
Ladan Mehran, Atieh Amouzegar, Seyed Mohsen Foroutan, Safdar Masoumi, Maryam Tohidi, Hengameh Abdi, Ali Aghaei, Amir Esmaeel Saghafinia, and Fereidoun Azizi
Springer Science and Business Media LLC
Abstract 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.
Mohammadjavad Honarvar, Safdar Masoumi, Ladan Mehran, Davood Khalili, Atieh Amouzegar, and Fereidoun Azizi
Springer Science and Business Media LLC
AbstractMetabolic syndrome (MetS), defined as the coexistence of interrelated cardiometabolic risk factors, is limited by ignoring the severity of the disease and individuals with a pre-metabolic state. We aimed to develop the first age- and sex-specific continuous MetS severity score in the adult population using confirmatory factor analysis (CFA) based on the MetS components in the Middle East. Using data from the population-based Tehran Lipid and Glucose Study (TLGS) I and II datasets, we conducted CFA of the single factor MetS on 8933 adults (20–60 years old) totally, and in age and sex subgroups. We allowed for different factor loadings across the subgroups to formulate age- and sex-specific continuous MetS severity score equations. Thereafter, we validated these equations in the dataset of TLGS III participants. Triglyceride had the highest factor loading across age and sex subgroups, indicating the most correlation with MetS. Except for women aged 40–60 years, waist circumference was the second most significant factor contributing to MetS. Systolic blood pressure was more closely related to MetS in women than in men. Systolic blood pressure and fasting plasma glucose had the weakest correlation with MetS among the 40–60 age group. Moreover, as women age, the contribution of fasting plasma glucose to MetS tended to decline, while it remained relatively constant in men. The resulting MetS severity score was correlated with age and homeostasis model assessment of insulin resistance. Furthermore, the continuous MetS severity score well predicted the traditional MetS according to receiver operating characteristic analysis in the validation dataset. The age- and sex-specific continuous MetS severity score for the West Asian adult population provides a tangible quantitative measure of MetS enabling clinicians to screen and monitor the individuals at risk and assess their metabolic trends.
Atieh Amouzegar, Mohammadjavad Honarvar, Safdar Masoumi, Maryam Tohidi, Ladan Mehran, and Fereidoun Azizi
The Endocrine Society
Abstract Context The evidence suggest that insulin resistance (IR) complicates chronic kidney disease (CKD); however, the longitudinal association of IR with development of CKD is unknown. Objective This work aimed to investigate the association between the dynamic course of insulin resistance and CKD. Methods In the longitudinal, population-based Tehran Lipid and Glucose Study, 3071 eligible participants aged 20 years or older were followed for 18 years at 3-year intervals. Homeostatic model assessment of insulin resistance (HOMA-IR) and clinical surrogate markers of IR, including triglyceride-glucose index (TyG), visceral adiposity index (VAI), and lipid accumulation product (LAP), were calculated. Using latent variable mixture modeling, sex-specific trajectories were plotted for each IR marker. Trajectory group association of the IR markers with CKD was determined using the multivariable Cox proportional-hazards regression model. Results For HOMA-IR, 2 distinct trajectory patterns (stable and increasing), and for TyG, VAI, and LAP, 3 trajectories (low, moderate, and high) were identified. The participants with an increasing HOMA-IR trajectory had a significantly increased risk of CKD in men (hazard ratio [HR]: 1.72; 95% CI, 1.06-2.79) and women (HR: 1.37; 95% CI, 1.00-1.89) after adjusting for confounding variables. The high TyG and VAI trajectory classes were associated with a higher risk of CKD than the low TyG and VAI trajectory classes both in men (TyG: HR: 1.97; 95% CI, 1.12-3.46; VAI: HR:1.66; 95% CI, 1.06-2.62) and women (TyG: HR: 1.50; 95% CI, 1.06-2.12; VAI: HR:1.66; 95% CI, 1.20-2.31). In contrast, the high LAP (HR: 3.38; 95% CI, 2.08-5.48) trajectory was associated with incident CKD only in women. Conclusion An increasing trend of HOMA-IR is associated with a higher risk of CKD in men and women. Among clinical IR surrogate markers, abnormal trajectory patterns of LAP in women and TyG and VAI in both sexes are associated with a higher risk of CKD.
Fereidoun Azizi, Hengameh Abdi, Ladan Mehran, Petros Perros, Safdar Masoumi, and Atieh Amouzegar
Elsevier BV
Seyedeh Melika Fanaei, Ladan Mehran, Atieh Amouzegar, Safdar Masoumi, Atefeh Amouzegar, and Freidoun Azizi
Wiley
BACKGROUND
Chronic kidney disease (CKD) can progress over time and cause renal replacement therapy. Studies showed an association between metabolic syndrome (MetS) and CKD. Current evidence is from cross sectional studies. There is a need for robust data from big prospective cohort studies with long-term follow-up. This study investigated the association between CKD and MetS after 18 years of follow-up.
MATERIAL AND METHOD
Among 15,255 participants aged ≥20 years at baseline (1999-2005), after exclusion of CKD, cancer, use of corticosteroid, 8987 participants entered the study and followed at a three-year cycle up to 2018. All participants were divided into five subgroups: (1) MetS free, (2) MetS+ (DM+, HTN-) (3) MetS+ (DM-, HTN+) (4) MetS+ (DM+, HTN+) (5) MetS+ (DM-, HTN-).
RESULT
At baseline the mean age of the participants was 39.8±13.3 y; 4996 (55.6%) were females. CKD was developed in 2,038 (22.7 %) subjects during 18 years of follow-up, of whom 1,107 had Mets. After adjusting for the confounding variables, MetS (DM+, HTN+) subgroup had the highest risk of CKD (HR=1.51, 95 % CI=1.32-1.71). MetS subjects with five components had higher incidence rate of CKD (HR=1.43, 95% CI= 1.22-1.68). There was no association between high waist circumference (WC) (HR=1.08, 95% CI=0.99-1.19) and high-density lipoprotein (HDL) (HR=1.07, 95% CI=0.98-1.18) with CKD.
CONCLUSION
CKD significantly develops in patients with MetS. Metabolic syndrome was associated with chronic kidney disease incidence at long term follow-up. Hypertension, diabetes and age were strong indicators, while abdominal obesity and reduced HDL were not associated with the incidence of CKD.
Elham Kazemian, Ladan Mehran, Safdar Masoumi, Atieh Amouzegar, and Fereidoun Azizi
Frontiers Media SA
ObjectivesThe current study aimed to examine how the trajectory of a body shape index (ABSI) could predict mortality in a prospective cohort of 5587 participants.MethodsA Growth Mixture Model (GMM) was employed to identify ABSI and body shape trajectories spanning from 2000 to 2018. Multivariate Cox regression models with hazard ratio (HR) and 95% confidence intervals (CIs) were built to assess the association of death from all-cause and cardiovascular disease (CVD) with ABSI and body shape trajectories.ResultsWe found that individuals with a low ABSI–marked increase (Class II) and high ABSI–marked increase trajectory (Class III) had a higher risk of all-cause (adjusted HR for Class II, 1.37; 95%CI, 1.04-1.79; adjusted HR for Class III, 1.42; 95%CI, 1.05-1.91) and non- CVD mortality (adjusted HR for Class II, 1.38; 95%CI, 1.00-1.91; adjusted HR for Class III, 1.42; 95%CI, 1.00-2.05) as well as an increased risk of CVD (adjusted HR for Class II, 1.40; 95%CI, 1.14-1.71; adjusted HR for Class III, 1.42; 95%CI, 1.13-1.78) and coronary heart disease (CHD) (adjusted HR for Class II, 1.52; 95%CI, 1.18-1.96; adjusted HR for Class III, 1.47; 95%CI, 1.11-1.95. The trajectories of body shape phenotypes did not show any significant associations with mortality, CVD, or CHD events.ConclusionsABSI trajectories might be associated with subsequent risk of mortality and CVD events.
L. Mehran, M. Honarvar, S. Masoumi, D. Khalili, A. Amouzegar, and F. Azizi
Springer Science and Business Media LLC
Fereidoun Azizi, Navid Saadat, Mir Alireza Takyar, Hengameh Abdi, Ladan Mehran, and Atieh Amouzegar
Korean Endocrine Society
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 (<i>P</i><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 (<i>P</i><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.
Ladan Mehran, Pouria Mousapour, Davood Khalili, Leila Cheraghi, Mohammadjavad Honarvar, Atieh Amouzegar, and Fereidoun Azizi
Springer Science and Business Media LLC
AbstractPrevious epidemiologic studies debated the association of body mass index (BMI) trends with cardiovascular disease and mortality. This study aimed to evaluate the association of BMI variability and slope with the incidence of Type 2 diabetes mellitus (T2DM) in a sex-stratified 15.8-year follow-up in the population-based Tehran Lipid and Glucose Study (TLGS). Of 10,911 individuals aged 20–60 years, 4981 subjects were included and followed for 15.8-years. The slope coefficient of BMI in the linear regression model represented individuals’ BMI trends up to the incidence of DM. The root mean squared error (RMSE) of the BMI linear trend was selected to reflect BMI variability through six follow-ups. Cox proportional hazards regression was used to investigate the association of the baseline BMI, BMI slope and RMSE with the incidence of T2DM among men and women. Multivariable-adjusted HRs of T2DM for each SD increment in BMI slope was 1.18 (95% CI: 0.94–1.48, p = 0.161) in normal weight men and 1.26 (95% CI: 1.10–1.44, p = 0.001) in overweight and obese men. However, in women, each SD increment in BMI slope increased the risk of T2DM with a HR of 1.19 (95% CI: 1.01–1.40, p = 0.039) in normal weight, and 1.14 (95% CI: 1.08–1.19, p < 0.001) in women with BMI ≥ 25 kg/m2. In men with a baseline BMI ≥ 25 kg/m2, BMI-RMSE was associated with a decreased risk of T2DM (HR: 0.71, 95% CI: 0.53–0.93, p = 0.015). Baseline BMI was not associated with the risk of diabetes in men and women. Positive BMI slope is associated with the development of diabetes in both sexes. The association of BMI variability with incident T2DM differs according to sex and baseline BMI. BMI variability is associated with a lower risk of T2DM in overweight and obese men. BMI variability in women and baseline BMI in both gender are not related to the risk of T2DM.
A. Amouzegar, M. Dehghani, H. Abdi, L. Mehran, S. Masoumi, and F. Azizi
Springer Science and Business Media LLC
Fereidoun Azizi, Navid Saadat, Hengameh Abdi, Ladan Mehran, Safdar Masoumi, Mir Alireza Takyar, and Atieh Amouzegar
Elsevier BV
F. Azizi, H. Abdi, L. Mehran, and A. Amouzegar
Springer Science and Business Media LLC
Following the conventional 12–18 month antithyroid drug (ATD) treatment in Graves’ disease (GD), 50% of patients experience relapse of hyperthyroidism. The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80 years. Articles were identified through the search of PubMed from January 1, 1941 to April 30, 2021. All study types were included. Articles were eligible if they reported data on the length of ATD treatment, particularly thyroid hormones and TSH receptor antibodies (TRAb) concentrations and specifically those with data on the remission and/or relapse rates. We described major progress regarding the duration of ATD therapy and related outcomes at every 20 years. Articles of 1941–1960 were mainly concerned with determination of favorable treatment, minimal effective dose, side effects and rate of remission after < 12-month ATD therapy. Studies with larger number of patients and longer follow-ups appeared in 1961–1980; higher remission rate after 18–24 months versus 6 months of ATD therapy was reported. Articles of 1981–2000 focused on identification of factors associated with high relapse rates after discontinuation of ATD. In 2001–2021, ATD became the first choice of treatment in many countries. However, 12–18 months of ATD therapy was arbitrarily chosen as the appropriate option. According to recent studies, persistent normalization of TRAb occurs after 5 years of methimazole therapy and ATD treatment of > 60 months could offer a 4-year remission rate of 85%. Long-term ATD treatment for more than 60 months is safe and effective, has the highest remission rate and cures most patients with GD; hence, it should be considered as the most appropriate duration for ATD therapy in these patients.
A. Amouzegar, E. N. Pearce, L. Mehran, J. Lazarus, M. Takyar, and F. Azizi
Springer Science and Business Media LLC
A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy.
Ladan Mehran, Negar Delbari, Atieh Amouzegar, Mitra Hasheminia, Maryam Tohidi, and Fereidoun Azizi
The Endocrine Society
Abstract Context Recently, reduced sensitivity to thyroid hormone as a more common finding in the general population and its possible association with metabolic parameters has been the focus of attention. Objective The objective was to evaluate the cross-sectional association of thyroid hormone sensitivity with diabetes, metabolic syndrome (MetS), and its components. Methods The study included a Tehranian representative sample of 5124 subjects aged ≥20 years participating in the Tehran Thyroid Study (2008-2011). Body weight, waist circumference, and blood pressure (BP) were measured, and serum concentrations of lipids and lipoproteins, fasting blood glucose, insulin, free thyroxine (fT4), and thyrotropin (TSH) were assayed. Thyroid hormone resistance was calculated by the Thyroid Feedback Quantile-based Index (TFQI) and Iranian-referenced Parametric TFQI (PTFQI) and compared with 2 other indices: Thyrotroph T4 Resistance Index (TT4RI) and TSH Index. Results TFQI was significantly associated with high BP MetS criterion (OR = 1.14, 95% CI: 1.06, 1.23) and diabetes mellitus (OR = 1.16, 95% CI: 1.04, 1. 30, P = .009) in euthyroid subjects after adjusting for age, sex, smoking, physical activity, body mass index, and Homeostasis Model Assessment Index for Insulin Resistance. TFQI was not associated with new-onset diabetes contrary to known diabetes in subgroup analysis. The results were similar for PTFQI. TSHI (OR = 1.22, 95% CI: 1.08, 1.38, P = .001) and TT4RI (OR = 1.08, 95% CI: 1.01, 1.16, P &lt; .001) were associated only with high BP in euthyroid subjects. Conclusion The new TFQI index seems to be the indicator of reduced sensitivity to thyroid hormone most suitable to associate its population variations with diabetes and hypertension in euthyroid subjects; however, interpretation for diabetes should be concerned with cautions, necessitating future studies.
Ladan Mehran, Atieh Amouzegar, Seyedeh Melika Fanaei, Safdar Masoumi, and Fereidoun Azizi
Elsevier BV
BACKGROUND
The contribution of anthropometric measures to predict mortality in normal-weight subjects is unclear. We aimed to study the association of central obesity measures, e.g., waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), with the risk of all-cause and CVD mortality.
METHODS
In a prospective population-based Tehran Lipid and Glucose Study, 8287 participants aged ≥30 y, followed for a median of 18 years. The association of WC, WHR and WHtR with the risk for mortality was estimated using multivariate Cox proportional hazard models in different BMI groups.
RESULTS
We documented 821 deaths, of which 251 were related to CVD mortality. Normal weight individuals with central obesity were significantly at increased risk of all-cause (HR: 1.5; 95% CI: 1.10, 2.1) and CVD mortality (HR: 1.6; 95% CI: 0.92, 2.9) compared with normal-weight individuals without central obesity; the risk remained significant only in women. Also, normal-weight women (not men) with high WHR were at increased risk of all-cause (HR: 1.7; 95% CI: 1.0, 2.8) and CVD mortality (HR: 5.9; 95% CI: 1.5, 23.2). High WHtR increased the risk of all-cause (HR: 1.5; 95% CI: 1.2, 1.8) and CVD mortality (HR: 1.8; 95% CI: 1.2, 2.7) which remained significant in normal-weight men and women. All central obesity indicators were significantly associated with all-cause and CVD mortality in subjects aged under 65.
CONCLUSION
Even in normal-weight individuals, WC and WHR in women and WHtR in both sexes are predictors of all-cause and CVD mortality. WHtR shows a stronger association, especially in the population aged under 65.
Mahdi Mahdavi, Atieh Amouzegar, Ladan Mehran, Elham Madreseh, Maryam Tohidi, and Fereidoun Azizi
Springer Science and Business Media LLC
Abstract Background Due to the increasing worldwide prevalence of obesity, it is essential to determine the prevalence of obesity-related thyroid dysfunctions. The purpose of this study was to investigate the prevalence of thyroid dysfunctions, namely hypothyroidism and hyperthyroidism, and their association with BMI among adult Iranian overweight and obese individuals. Method This cross-sectional study was carried out within the framework of the Tehran Thyroid Study (TTS); 5353 participants (57.5% female) entered our study. Anthropometric measurements were performed. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were assayed. We categorized individuals into 3 BMI groups (normal-weight, overweight and obese), then calculated prevalence rate, odds ratio (OR), and 95% confidence interval (CI) for outcomes in overweight and obese groups. The normal-weight group was used as the control group. Results We found a higher prevalence of hypothyroidism (11.6% vs 8.2% Total, 4.0% vs 1.1% overt and 7.6% vs 7.1% subclinical, P < 0.001) and TPOAb positivity (17.3% vs 11.6%, P < 0.001) in obese participants compared with normal-weight participants. Hyperthyroidism’s overall prevalence was 4.2, 5.7, and 4.9% in obese, overweight, and normal-weight groups, respectively. Obesity was associated with higher odds of overt hypothyroidism (OR: 2.0, 95% CI: 1.15–3.49, P < 0.05) and TPOAb positivity (OR: 1.29, 95% CI: 1.04–1.60, P < 0.05) after adjusting for confounding variables. In contrast, no association was observed between the overweight group and the odds of hypothyroidism and TPOAb positivity in the adjusted results. Conclusions Obesity was associated with an increased risk of overt hypothyroidism and TPOAb positivity.
Ladan Mehran, Fereidoun Azizi, Pouria Mousapour, Leila Cheraghi, Shahin Yarahmadi, Golshan Amirshekari, and Davood Khalili
Springer Science and Business Media LLC
To develop a risk prediction model for early discrimination between transient and permanent congenital hypothyroidism (CH). In a retrospective cohort, 1047 confirmed CH neonates, from 15 randomly selected provinces in Iran, were entered to the study. Clinical and biochemical information of transient and permanent cases, distinct at the age of 3 years were retrospectively gathered. Among CH neonates, the overall prevalence of permanent CH was 57.1%. Using forward stepwise multivariable logistic regression analysis, confirmatory venous TSH, total T4 < 8.2 ng/dl, requiring levothyroxine dosage increase, venous TSH ≥ 10 mU/l between 6 and 12 months of age, parental consanguinity and family history of thyroid diseases were associated with increased risk of permanent CH. The prediction model achieved a very good power in discriminating patients with transient and permanent CH with an optimism-corrected area under the ROC curve of 0.86 (95% CI:0.84–0.88) with a very good calibration. Integrated discrimination improvement (IDI) test indicated significantly greater diagnostic performance of the model compared to serum TSH alone. Using several potential predictors for permanent CH, we developed a relatively powerful risk prediction model as a cost-saving screening tool in order to avoid unnecessary long-term treatment of transient cases which might empower clinicians for prognostication of the CH course and tailoring treatment up to 1 year of age.
Ladan Mehran, Atieh Amouzegar, Hengameh Abdi, Negar Delbari, Elham Madreseh, Maryam Tohidi, Mohammad Ali Mansournia, and Fereidoun Azizi
S. Karger AG
<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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) &#x3c;0.1 and &#x3e;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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.
Ladan Mehran, Atieh Amouzegar, Safoora Gharibzadeh, Hengameh Abdi, Mohammad Ali Mansournia, Maryam Tohidi, and Fereidoun Azizi
Georg Thieme Verlag KG