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Abstract Body mass index (BMI) is a well-known risk factor for type 2 diabetes mellitus (T2DM). We aimed to identify BMI trajectory patterns and evaluate their association with T2DM during 18 years of follow-up. We included 6026 participants aged 20 to 65 from the prospective population-based Tehran Lipid and Glucose Study (TLGS). The BMI trajectory patterns were identified using latent growth mixture modeling (LGMM) during the measurement period. The association between the BMI trajectory patterns and future T2DM was evaluated using the Cox proportional hazard regression models. Three BMI trajectory patterns of low-increasing (38.6%), medium-increasing (47.1%), and high-increasing (14.3%) were detected. The participants in the medium-increasing and high-increasing BMI trajectory groups had HRs of 1.87 (95% CI 1.53–2.28) and 3.41(95% CI 2.71–4.29) for T2DM incidence, respectively. Within the normoglycemic subpopulation, the high-increasing BMI group had an HR of 3.82 (95% CI 2.79–5.24) compared to the low-increasing BMI group, while in the prediabetic subpopulation, the high-increasing BMI group had an HR of 2.93 (95% CI 2.04–4.19) compared to the low-increasing BMI group. Body weight varies in a relatively stable pattern in adulthood over the long-term period. Medium and high-increasing BMI trajectory patterns have a significantly increased risk for future T2DM in both normoglycemic and prediabetic individuals. Identifying BMI trajectory patterns can help healthcare providers in early prediction, risk assessment, and monitoring strategies development for the prevention of T2DM.

Abstract Background Understanding the relationship of thyroid hormones with the development of chronic kidney disease (CKD) has important clinical implications for managing patients with both thyroid and kidney dysfunction. In this review, our purpose was to provide a thorough comprehension of the interplay between thyroid hormones, thyroid dysfunctions, and CKD. Summary While there is evidence linking thyroid hormone levels to renal diseases, the association between thyroid hormones, specifically within the normal range, and the risk of CKD incidence is still a subject of debate. The Google Scholar, PubMed, Scopus, and Web of Science, were searched using the medical subject heading (MeSH) terms for the relevant keywords up to December 2023. Conclusion Based on the review, the development of CKD is more consistently associated with higher serum TSH and thereafter lower serum free T3 levels; however, its association with free T4 is more controversial. Furthermore, subclinical and overt hypothyroidisms were considerably associated with incident CKD. Hyperthyroidism and Hashimoto thyroiditis might increase the risk of CKD.

BackgroundType 2 diabetes mellitus (T2DM) poses a significant public health challenge, contributing to considerable morbidity and mortality worldwide, which necessitates urgent preventive measures. Thyroid disorders, prevalent in many individuals, are intricately linked to metabolic health, yet studies on their relationship with T2DM yield inconsistent results—some suggesting an increased risk with abnormal thyroid hormone levels, while others indicate potential protective effects. This study investigated the association between changes in serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels and the incidence of type 2 diabetes mellitus.MethodsData from 1938 individuals aged ≥20 in the Tehran Thyroid Study cohort were used, spanning four examination cycles from 1999 to 2012, with three-year intervals. TSH and FT4 levels were log-transformed and modeled as time-varying exposures to study their association with incident T2DM.ResultsDuring a median follow-up of 9.43 years, 135 new T2DM cases were identified. The multivariable-adjusted joint model (JM) revealed that each unit increase in log-transformed TSH level was associated with a 25% decrease in T2DM incidence [HRs (95% CI): 0.75 (0.64-0.90)]. Conversely, each unit increase in FT4 level showed a marginally significant higher risk [1.06 (0.99-1.13); p-value=0.06].ConclusionThe findings of this study suggest that dynamic changes in serum thyroid hormones are associated with the development of T2DM. Rising TSH and decreasing FT4 over time are associated with a lower risk of diabetes. These findings suggest a complex interplay between thyroid function and the risk of T2DM, emphasizing the importance of monitoring thyroid hormone levels as a part of T2DM prevention strategies.

Objectives This study aimed to investigate the association between age-specific and sex-specific continuous metabolic syndrome severity score (cMetS-S) and the risk of developing type 2 diabetes mellitus (T2DM). Additionally, the study aimed to assess the added value of cMetS-S in predicting T2DM compared with traditional MetS criteria.Design The study used a longitudinal cohort design, following participants for 18 years.Setting The research was conducted within the Tehran Lipid and Glucose Study, a community-based study in Tehran, Iran.Participants A total of 6957 participants aged 20–60 years were included in the study.Interventions/exposures The cMetS-S of each participant was determined using age-specific and sex-specific equations and Cox proportional hazard regression models were used to analyse the association between cMetS-S and T2DM using continuous and quantile approaches.Primary and secondary outcome measures The outcome measure was the association between cMetS-S and the development of T2DM during the 18-year follow-up.Results A total of 1124 T2DM cases were recorded over 18 years of follow-up. In the fully adjusted model, a 1-SD increase in the cMetS-S was associated with future T2DM (HR 1.72; 95% CI 1.54 to 1.91). Men and women had HRs of 1.65 (95% CI 1.40 to 1.95) and 1.83 (95% CI 1.59 to 2.10) for T2DM per 1-SD increase in cMetS-S, respectively. Higher cMetS-S was associated with increased risk of diabetes in both prediabetic (HR 1.42;95% CI 1.23 to 1.64) and normoglycaemic individuals (HR 2.11;95% CI 1.76 to 2.54); this association was more significant in normoglycaemic individuals. Unlike the traditional-based MetS definitions, the cMetS-S improved diabetes prediction (p

AimWe aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association.MethodParticipants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined.ResultsA total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association.ConclusionHigh BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

Abstract Type 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

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.

Abstract Background Struma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer. Case presentation We described a 47-year-old multigravida woman with bilateral adnexal and lower abdominal wall masses detected during the evaluation of abnormal uterine bleeding. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and surgical removal of abdominal wall mass. Then, the pathological evaluation revealed papillary thyroid carcinoma (PTC) within struma ovarii and metastatic PTC in the abdominal wall fibro adipose tissue. Further, cervical thyroid gland physical examination and ultrasound illustrated a nodule within the left lobe. Subsequently, a total thyroidectomy was performed, and a histological examination revealed PTC. Furthermore, all affected tissue, i.e., struma ovarii, abdominal wall metastasis, and cervical thyroid gland tested for BRAF and RAS mutations and RET/PTC 1 rearrangement. RET/PTC 1 rearrangement was identified among all three different sites. Finally, after six years of follow-up, the patient had no evidence of recurrence or distant metastasis. Conclusions In light of these findings, malignant struma ovarii might yield a clue to cervical thyroid carcinoma, and the molecular analysis could provide valuable information for understanding the underlying mechanism, tumor clinicopathological behaviors, and prognosis.

Abstract Traditional 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

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.

Abstract Aims We investigated whether thyroid function could be associated with obesity phenotypes amongst euthyroid individuals. Materials and methods A cross-sectional analysis was conducted among healthy, euthyroid subjects. The study participants were chosen from the Tehran Thyroid Study (TTS). We analyzed 2988 euthyroid adults and classified them into four obesity phenotype groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). The statistical differences between thyroid hormones between various obesity phenotypes according to age and sex was compared using analysis of covariance (ANCOVA). Results It was found that MHNW participants had higher levels of FT4 when compared with metabolically healthy or unhealthy obese subjects (P 0.05). Conclusion “Metabolically abnormality” was independently related to low normal FT4 levels in overweight/obese euthyroid individuals. There is a need for further research to understand how low FT4 levels are linked to metabolically unhealthy states in euthyroid individuals.

Abstract Metabolic 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.

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.

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

Abstract Previous 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

PurposeThe association between metabolic phenotypes and thyroid function has not yet been established; therefore, this study examined whether different metabolic phenotypes are associated with the development of hypothyroidism.MethodsStudy participants were selected from the Tehran Thyroid Study (TTS). A total of 3338 euthyroid adults were included and categorized into four obesity phenotype groups: metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). The participants were assessed at baseline and during three follow-up studies at three-year intervals. Multiple logistic regression analysis was used to examine the relationship between metabolic phenotypes and the development of hypothyroidism.ResultsIn the total population, the chi-square test was only significant (P=0.008) in 3rd year with a higher prevalence of hypothyroidism in the MUNW phenotype, followed by MHO, MUO, and MHNW. Moreover, in the 3rd and 9th years of follow-up, hypothyroidism was more prevalent in MUO only in male subjects (P=0.002 and 0.035, respectively). In the unadjusted model, the MHO phenotype increased the odds of hypothyroidism compared with the MHNW phenotype (OR=1.51; 95% CI=1.04, 2.18; P-value=0.031). After adjusting for confounding factors, the odds of hypothyroidism were higher in the MUNW (OR=1.86; 95% CI=1.17, 2.96; P-value=0.008), MHO (OR=1.71; 95% CI=1.09, 2.67; P-value=0.018), and MUO (OR=1.64; 95% CI=1.03, 2.62; P-value=0.036) phenotypes than in the MHNW group. The MUNW phenotype increased the risk of hypothyroidism compared to MHNW, only in males. However, in females, the MHO phenotype increased the risk of hypothyroidism compared to MHNW.ConclusionBoth obesity and metabolic abnormalities are associated with hyperthyroidism. Healthy metabolic and weight maintenance were associated with a lower risk of hypothyroidism in males and females.

It is currently debated whether vitamin D requirements during pregnancy differ from those during non-gravid states. In current analyses, we aimed to determine the best model for the association between PTH and serum 25-hydroxyvitamin D (25(OH)D) and the threshold for circulating 25(OH)D at which serum parathyroid hormone (PTH) is suppressed. This multicenter prospective cross-sectional study was conducted on 227 Iranian pregnant women aged 15–45 years in their third trimester of pregnancy. The locally weighted smoothing scatter plot (LOWESS) was used to determine the curvilinear shape of the 25(OH)D/PTH relationship. Linear and non-linear methods were employed to determine the best fit and cut-point for serum 25(OH)D concentration. The median serum 25(OH)D and corresponding serum PTH concentration were 17⋅26 (13⋅44–23⋅08) ng/ml and 19⋅46 (15⋅08–25⋅04) pg/ml in our study population, respectively. The LOWESS curve suggested a non-linear and monotonic with a negative slope relation between PTH (pg/ml) and serum 25(OH)D (ng/ml). The optimal model for the association between PTH and serum 25(OH)D was a one-term fractional polynomial (FP1) (AIC = 1640⋅463). The FP1 analysis identified the 25(OH)D threshold of 12⋅48 ng/ml at which serum PTH rapidly rose. The expected degree of PTH stimulation seems to have a linear trend as 25(OH)D falls below 40 ng/ml. 25(OH)D (ng/ml) and PTH (pg/ml) had a non-linear and monotonic relationship with a negative slope. Our data suggest that a 25(OH)D threshold of 12⋅48 ng/ml is sufficient for parathyroid hormone suppression, which could be used to screen for deficient individuals.

Abstract Background Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the most important differential diagnosis of parathyroid hormone (PTH)-dependent hypercalcemia. The clinical features of FHH and PHPT can overlap in some cases. Therefore, these two diseases must be differentiated to prevent unnecessary parathyroidectomy. Here, we present a case that was not entirely matched with any of the known differential diagnoses of hypercalcemia. Case presentation A 19-year-old girl with no history of any disease presented with persistent hypercalcemia without any specific musculoskeletal complaint. We found persistent hypercalcemia in her routine laboratory data from 3 years ago; while no data was available during the childhood period. Her dietary calcium intake was normal. She did not mention any history of renal stone, bone fracture as well as family history of hypercalcemia. Biochemical features showed normal values of serum creatinine, high normal serum calcium (range, 10.3–11.3 mg/dL; (normal range: 8.8–10.4)), and non-suppressed PTH levels (range, 37.2–58.1 pg/mL; (normal range: 10–65)). Serum 25 OH vitamin D level at the first visit was 16.1 ng/mL that treated by vitamin D supplementation. Since then, all 25 OH vitamin D levels were in the acceptable range. After correction of vitamin D deficiency during the follow-up period the calcium creatinine clearance ratio(s) (CCCR) were calculated in the range of 0.009 to 0.014 (means below 1%). The clinical and laboratory data indicate more FHH rather than PHPT. Genetic studies were negative for the common genes associated with FHH (CASR, GNA11, and AP2S1 genes) and multiple endocrine neoplasia type1 (MEN1). On the other hand, no evidence of autoimmunity was found in her to support an autoimmune FHH-like syndrome. Hence, the case did not match completely to any diagnosis of FHH and PHPT, so we decided to follow her. Conclusion We presented a patient with FHH phenotype whose common genetic tests were negative. Further research is needed to ascertain other causes leading to similar manifestations.

Abstract Background Both human genes and environmental exposures, due to complex interplay, play important role in the cancer etiology. Vitamin D is associated with a reduced risk of incidence and mortality of several human cancers. This study will aim to investigate the possible effects of individual polymorphisms in vitamin D receptor (VDR) as well as effects of VDR haplotypes on response to vitamin D supplementation in breast cancer survivors. Methods This is an interventional study in which the effects of vitamin D supplementation on plasma vitamin D levels, inflammatory and antioxidant biomarkers and factors associated with cell proliferation, differentiation, damage, and apoptosis will be investigated stratified by variations in VDR genotype. The present study will be conducted on breast cancer survivors referred to the Shohadaye Tajrish hospital and its associated clinics. One hundred ninety-eight breast cancer survivors will receive 4000 IU of vitamin D3 daily for 12 weeks. VDR Fok1, ApaI, TaqI, BsmI, and Cdx-2 genotype will be determined at the end of the study and responses to vitamin D supplements (inflammatory, antioxidant, cell proliferation, differentiation, damage, and apoptosis biomarkers) will be compared between the three subgroups of each VDR polymorphism as well as different VDR haplotype categories. Discussion Genetic variation is a fundamental factor influencing individuals’ divergent responses to diet, nutritional status, metabolic response, and diet-related health disorders. Furthermore, studies of gene and environment interactions will provide a precise and accurate assessments of individuals’ dietary requirements by considering both the genetic and environmental aspects simultaneously. The results of the current study, to some extent, will highlight the discrepancies existing in the findings of different studies regarding vitamin D, VDR, and cancer by considering both the genetic and environmental aspects simultaneously. If responses to vitamin D supplementation could be modified by VDR SNPs, determining the distribution of VDR polymorphisms in both breast cancer survivors and healthy populations will provide a new insight into the vitamin D requirements of individuals to prevent cancer and its related mortality based on their genotypes. Trial registration This trial has been registered on Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153

Primary hyperparathyroidism (PHPT) is the most prevalent cause of hypercalcemia, affecting 0.3% of the population. The only curative procedure is parathyroidectomy. Persistent PHPT occurs in 4.7 percent of patients, even in the most skilled hands. Ectopic adenomas are challenging to localize before and during surgery and frequently result in persistent PHPT. We presented a case with persistent PHPT due to lung parathyroid adenoma that was successfully resected with video-assisted thoracoscopic surgery. A 55-year-old female patient was admitted to our endocrinology clinic with persistent PHPT after four neck explorations over 16 years. The last 99m Tc-MIBI scintigraphy with SPECT showed nothing suggestive of parathyroid adenoma, neither in the neck nor the mediastinum, but a solitary nodule as an incidental finding was reported in the lower lobe of the right lung, which was highly probable for a parathyroid adenoma in a fluorodeoxyglucose PET scan. Pathological examination ruled out parathyromatosis and lung malignancy; despite its location outside the anticipated embryonic pathway, pathology revealed the presence of an ectopic parathyroid adenoma. After the surgery, serum parathyroid hormone and calcium levels decreased, and hypoparathyroidism was corrected with calcium carbonate and calcitriol.

Abstract Background Thyroid autoimmunity(TAI) is the most prevalent autoimmune condition in women of fertile age. There are increasing data regarding the association of thyroid dysfunction and thyroid autoimmunity with adverse pregnancy outcomes but there is no consensus regarding infertility and TPOAb positivity; thus we aimed to evaluate the association between thyroid TPOAb positivity and infertility in females and males in a population-based study (TTS). Methods Cross-sectional study of 3197 female and male participants in Tehran Thyroid Study (TTS) at the framework of the Tehran Lipid and Glucose Study (TLGS). Data included biochemical measurements and a self-administered questionnaire. Results A total of 12,823 cases in phase 4, 3719 cases (2108 female and 1611 male) were analyzed. The mean TSH of the infertile female and male was 2.52 ± 2.68 μIU/ml and 3.24 ± 10.26 μIU/ml respectively. The TPO median(IQR) of women with and without a history of infertility were 6.05 (3.30–13.96)and 6.04 (3.17–11.15);(P = 0.613), they were 5.08 (3.20–125.68) and 5.31 (3.93–125.68);(P = 0.490) in male participants, respectively. Results of crude and adjusted logistic regression analysis of the development of infertility by thyroid function and TPOAb, except for fT4 in male subjects, depicted no association between infertility and other variables in both crude and adjusted models. Conclusion Based on the result, thyroid autoimmunity was not associated with infertility in both females and males.

Abstract 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 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

Abstract 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 Introduction Despite the evidence available on the adverse impact of gestational diabetes (GDM) and thyroid disorders on developing type 2 diabetes (T2DM), the concurrent influence of these disorders on the incidence of T2DM has not been reported yet. Methods In this prospective study, 1894 non-diabetic women aged 20 to 60 years, with a history of at least one term delivery, without diagnosed hyperthyroidism were selected at the initiation of the Tehran Thyroid Study (TTS). Pooled logistic regression analyses were used to investigate the association of GDM, thyroid disorders i.e., hypothyroidism and/or thyroid peroxidase antibody (TPOAb) positivity and interaction between GDM and thyroid disorders with the risk of incident T2DM. Results Of the 1894 participants of the present study, 346 (18.3%) had a history of GDM, and 832 (43.9%) had thyroid disorders. The total cumulative incidence rate of T2DM at the median follow-up time of ~ 12 years was overall 12/1000 person-years (95% confidence interval (CI): 10/1000–13/1000), with an incidence rate of 16/1000 (95%CI: 13/1000–20/1000) in women with GDM; and 11/100,000 (95%CI: 9/100,000–12/1000) among those without GDM. After adjustment for age, the risk of incident T2DM increased among individuals with the previous GDM compared to women without a history of GDM (odds ratio (OR): 1.54, 95%CI: 1.06, 2.25). No significant associations were found between either thyroid disorders or the interaction between GDM and thyroid disorders with the development of T2DM; (OR: 1.14, 95%CI: 0.82, 1.58) and (OR: 1.27, 95%CI: 0.66, 2.43), respectively. Conclusion GDM and thyroid disorders have no concurrent impacts on the incidence of T2DM.

Abstract Objective We investigated whether vitamin D receptor (VDR) polymorphisms are associated with circulating metabolic biomarkers and anthropometric measures changes in breast cancer survivors supplemented with vitamin D3. Methods One hundred sixty-eight breast cancer survivors admitted to Shohaday-e-Tajrish hospital received 4000 IU of daily vitamin D3 supplements for 12 weeks. Anthropometric measurements as well dietary, physical activity and plasma metabolic biomarkers assessments were performed before and after intervention. VDR polymorphisms were considered as the main exposures. Multivariate multiple linear regression analyses were used to determine the association between the VDR single-nucleotide polymorphisms (SNPs) and changes in metabolic and anthropometric measures in response to vitamin D3 supplementation. Results One hundred twenty-five (85%) women had insufficient and inadequate levels of plasma 25-hydroxy vitamin D (25(OH)D) at baseline. Compared to the AA genotype of the ApaI, the aa category showed greater increase in muscle mass [71.3(10.7131.9)] and higher decrease in LDL-C [− 17.9(− 33.6, − 2.3)] levels after adjustment for potential confounders. In addition, the heterozygous genotype (Bb) of the BsmI VDR was associated with higher increase in WC following vitamin D3 supplementation, compared to BB [2.7(0.1,5.3)]. Haplotype score analyses indicate a significant association between inferred haplotypes from BsmI, ApaI, TaqI and FokI, BsmI and Cdx2 VDR polymorphisms and on-study visceral fat changes. Conclusions Findings of this study showed that genetic variation in the VDR gene was associated with changes in cardio-metabolic parameters in breast cancer survivors, supplemented with vitamin D3, results could provide a novel insight into better understanding of which subset of individuals benefit most from normalization of vitamin D status. Trial registration This trial has been registered on the Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153 and was approved by the ethics committees of the National Nutrition and Food Technology Research Institute (NNFTRI), Shahid Beheshti University of Medical Sciences (SBMU).

Abstract Background Despite the strong association of smoking with cardiovascular disease (CVD) and cerebral stroke, the consequences of smoking have not been elucidated among Iranian populations. This study aimed to assess sex-specific incidence of CVDs among an urban Iranian population with different smoking habits. Methods Participants were recruited from the Tehran Lipid and Glucose Study (TLGS). Data on socio-demographic features and smoking habits from a sample of 10,400 individuals (4378 men and 6022 women), aged ≥20 years without prior CVD history were analyzed. Participants were followed up for 12 years for incidence of CVD/CHD events. Men were categorized in six groups, including never-, passive, ex-, passive and ex-, occasional and daily smokers. Women were categorized in three groups, i.e. never smokers, passive smokers and ever smokers. Using cox regression model, adjusted hazard ratios (HRs) of incident CVD/CHD were calculated for each group, given never smokers as the reference. Results In men, HR of CVD was 1.13 (95%CI: 0.80–1.59) in passive smokers, 1.23 (95%CI: 0.91–1.66) in ex-smokers, 1.46 (95%CI: 0.90–2.36) in passive and ex-smokers, 2.33 (95%CI: 1.25–4.33) in occasional smokers and 2.05 (95%CI: 1.57–2.67) in daily smokers. In smokers of ≥21 cigarettes/day, HR of CVD was 3.79 (95%CI: 2.25–6.37), with less risk observed in those who smoked lesser numbers of cigarettes/day. Quitters of ≥15 years were almost risk free. In women, none of the HRs of CVD/CHD were significant. Conclusion An increased risk of incidence of CVD/CHD was found in current male smokers. To confirm and further elaborate these findings, more data of sex-specific studies are required from culturally diverse urban and rural areas of Iran.

Abstract Background Data on the effects of motivational interviewing (MI) on modifying unhealthy lifestyles and promoting weight status during childhood is controversial. Adolescents are more prone to assume higher personal responsibilities for behavioral changes. This study aims to investigate whether MI will improve weight management process in adolescents. Methods/design A systematic review will be conducted on clinical trials, assessing the effect of MI on weight management processes in adolescents, aged 10 to 19 years. The primary objective is to assess the efficacy of MI in controlling weight-related measures in overweight and obese adolescents. Secondary objectives are assessing the efficacy of MI on obesity-related behaviors and cognitive abilities considering heterogeneity in outcomes of primary studies in different MI settings. Main data sources include MEDLINE/PubMed, Scopus, Embase, Web of Science, Cochrane, and PsycINFO from 1980 to May, 2018, with no language restrictions. Study selection, data extraction, and risk of bias assessment will be performed by two independent reviewers. A meta-analysis will be conducted on relevant outcomes. Data will be analyzed for outcome of interest using the 95% confidence interval (CI) of an estimate for dichotomous outcomes and mean differences (MDs) for continious outcomes. Cochrane’s Q statistic and the I 2 statistic will be performed to evaluate the heterogeneity. Subgroup analysis and suitable analytical strategies will be conducted to identify the potential sources of heterogeneity. As we expect a high heterogeneity in our included studies, pooled risk ratios (RRs) and 95% CI will be calculated to estimate the overall effect sizes, using meta-regression models or finite mixture modeling through conducting random effect methods. GRADE system will be used to evaluate the certainty of evidence. We will also use subgroup analysis and the GRADE system to investigate the effect of methodological quality of primary studies on results of meta-analysis. Funnel plots and egger and beggs test and plot will be implemented to assess publication bias. Discussion The results of this systematic review will provide more insights regarding the effect of MI on weight management in adolescents and will be useful for future research and health promotion programs in this age group. Systematic review registration PROSPERO 2017:CRD42017069813.

ContextWhile the role of overt hypothyroidism in lipid disorders is clear, the association between dyslipidemia and subclinical thyroid diseases remains unclarified.ObjectiveTo examine lipid trends based on thyroid function over a 10-year period.DesignThis is a prospective population based cohort study.SettingGeneral community.Participants2383 euthyroid participants, as well as those with subclinical thyroid diseases, in all residents of district 13 of Tehran were examined. Subjects who were on levothyroxine, anti-hyperthyroid drugs, and glucocorticoids, those with a history of thyroid surgery or RAI and pregnant women were excluded.Main outcome measuresLipid trends in Model 1 were adjusted for age and follow up duration, and in Model 2 gender-specific multivariate adjustments were performed for thyroid status, diabetes mellitus, smoking status, education, BMI, lipid lowering medications, age and follow up duration by using generalized estimating equations.ResultsIn every four years of assessments, there were significant decreases in levels of all lipid parameters (all Ps ConclusionDuring a 10 year follow-up, decrescendo trends were observed in levels of total cholesterol, triglycerides, which were not be accounted for by the consumption of lipid lowering drugs and thyroid status.

[This corrects the article DOI: 10.1371/journal.pone.0216389.].

Thyroid peroxidase antibody (TPOAb), the most common antibody frequently measured in population surveys is a protein expressed in the thyroid gland. We conducted the present study to analyze the prevalence and incidence of thyroid auto immunity and natural course of TPOAb in a population based study.This prospective study was conducted within the framework of the Tehran Thyroid Study (TTS) on 5783 (2376 men and 3407 women) individuals aged ≥ 20 years who had thyroid function tests at baseline and were followed up for median 9.1 year with TPOAb measurements at approximately every 3 years.The mean age of total population at baseline was 40.04±14.32. At baseline, of the 5783 participants, 742 (12.8%) were TPOAb positive, with higher prevalence among women than in men (16.0 vs. 8.5%, p = 0.001). The prevalence of TPOAb positivity in the total population was 11.9, 14.9 and 13.6% in the young, middle age and elderly respectively. The total incidence rate (95%CI) of TPOAb positivity in the total population (5020) was 7.1 (6.36-7.98) per 1000 person-years of follow-up, with higher incidence of TPOAb positivity among young participants, i.e. 8.5 (7.5-9.7) per 1000 person-years. Sex specific incidence rate demonstrated that TPOAb positivity was higher in women, 9.3 (8.2-10.7) per 1000 person-years. The Cox's proportional hazard model analysis showed that the hazard ratio of developing TPOAb positivity was higher in women than men (P

Following publication of the original article [1], the authors reported that one of the co-authors has a mistake in the author name.

Background: Physical activity (PA) is associated with the metabolic syndrome (MetS) and its components. This study aimed to examine the association between PA and MetS and its components among normal weight and overweight/obese adolescent in Tehran Lipid and Glucose Study (TLGS). Methods: This cross-sectional study includes 777 adolescents, aged 12-18 years, who were selected by multi-stage random cluster sampling from among TLGS participants. Subjects were classified as normal weight and overweight/obese based on the age- and sex-specific standardized percentile curves of BMI for Iranian population. Levels of PA were assessed using a standardized and modifiable activity questionnaire (MAQ), and categorized into tertiles. MetS was defined according to the Cook′s criteria. Results: Prevalence of the MetS was higher in overweight/obese than normal group (35% vs. 3%; P: 0.02). Normal groups were more physically active (50% vs. 44%); however, difference was not significant. There was a significant association between the light PA and risk of lower level of HDL-C before and after adjustment, in normal weight group (OR: 1.61, CI 95%: 1.11, 2.35; OR: 1.65, CI 95%: 1.12, 2.44, respectively). The overweight/obese group with light and moderate PA had a higher risk of having abdominal obesity than those with vigorous PA, only after adjustment for determined covariates (OR: 1.11, CI 95%: 1.07, 1.21; OR: 1.06, CI 95%: 1.01, 1.08, respectively); the association between MetS and PA was not significant. Conclusions: The results of this study confirm the association between PA and some individual components of MetS such as waist and HDL-C.

Background. Type 2 diabetes is an increasingly common condition with several preventable microvascular complications such as kidney damage. Nephropathy is expensive to manage, especially as hospital dialysis treatment. Improving patients’ knowledge, attitude, and practice (KAP) toward their condition can achieve better control, delay complications, and improve their quality of life. This study evaluated the KAP and self-care behaviors of diabetic patients on dialysis and variables that affect it. Methods. This cross-sectional study was conducted at Shahid Beheshti academic hospitals of Tehran, Iran. Face-to-face interviews were held to fill five validated questionnaires: three evaluating KAP, one evaluating self-management, and one evaluating quality of life. Result. 117 diabetic patients on hemodialysis (42 females) with mean (SD) age of 68.70±9.26 years were enrolled in the survey. The scores for patient’s KAP, self-care, and quality of life were 59.90±11.23, 44.27±8.35, 45.06±12.87, 46.21±10.23, and 26.85±13.23, respectively. There was significant negative correlation between patients’ knowledge and attitude with their glycosylated hemoglobin level and their fasting blood sugar. There was significant correlation between patients’ knowledge and practice with their self-care activities. Conclusion. The present study suggests that patients’ KAP scores have a practical effect upon self-care behavior. This highlights the needs for effective diabetes education programs in developing countries like Iran.