Trajectory patterns of metabolic syndrome severity score and risk of type 2 diabetes.

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.

The impact of metabolic syndrome on chronic kidney disease development. Insights from a big prospective study.

BACKGROUND: Chronic kidney disease (CKD) can progress over time and cause renal replacement therapy. Studies showed the association between metabolic syndrome (MetS) and CKD. Current evidence is from cross-sectional studies. There is a need for the 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, and use of corticosteroids, 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+) and (5) MetS+ (DM-, HTN-). RESULT: At baseline, the mean age of the participants was 39.8 ± 13.3 years; 4996 (55.6%) were females. CKD was developed in 2038 (22.7%) subjects during 18 years of follow-up, of whom 1107 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 a 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 the development of chronic kidney disease incidence. Hypertension, diabetes, and age were strong indicators, while abdominal obesity and reduced HDL were not associated with the incidence of CKD.

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

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

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

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

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

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

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

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

Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study.

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.

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

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

Long-Term Variations of Antithyroperoxidase Antibodies and its Clinical Significance.

Various cut-offs have been proposed for thyroid peroxidase antibodies (TPOAb) positivity. Considering that the long-term trend of TPOAb levels and its positivity incidence is not clearly understood, we conducted the current study to determine the longitudinal variations of TPOAb in a population-based cohort study. We followed 5783 individuals of Tehran Thyroid cohort Study (TTS) for 10 years (4 phases). After exclusions, data of 3493 euthyroid participants remained for analyses. The baseline prevalence rates of TPOAb positivity were 19.8, 17, and 11.4% and the annual incidence rates (95% CI) of TPOAb positivity were 8.53 (8.29-8.77), 7.59 (7.37-7.80) and 6.79 (6.60-6.98) per 1000 persons for the 3 proposed cut-offs of 14.77, 18.38, and 40 U/l; respectively. Although a slightly increasing trend was observed for TPOAb levels (p=0.001) and its conventional positivity (TPOAb>40U/l), the recently proposed cut-offs of 14.77 and 18.38 U/l showed constant TPOAb positivity over 10 years. The time trends of the TPOAb levels among younger participants were significantly different from older participants (time×age effect p=0.004), with the former having an increasing trend and the latter, a relatively decreasing trend. Although the prevalence of TPOAb positivity was significantly (p<0.001) higher among women as compared to men, the longitudinal changes of TPOAb were similar in men and women. TPOAb positivity along with TSH values between 2.5 and 5.0 mU/l or free T4 values between 0.93 and 1.7 ng/dl exerted a significantly increased risk of subclinical or overt hypothyroidism. In an iodine sufficient population, an increasing trend in TPOAb levels was observed in line with the increasing incidence of subclinical and overt hypothyroidism.

Associations Between Thyroid and Blood Pressure in Euthyroid Adults: A 9-Year Longitudinal Study.

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.

Thyroid Dysfunction States and Incident Cardiovascular Events: The Tehran Thyroid Study.

The objective of the study was to investigate the relation of different thyroid function states with the incidence of cardiovascular disease (CVD)/coronary heart disease (CHD) among a Middle-Eastern population with a high incidence of CVD/CHD. A total of 3975 participants entered the study (43.6% men). According to their thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels, the participants were categorized into 5 groups: euthyroid, subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism. Multivariable Cox proportional hazard models were used to assess the relation of different thyroid function states with incident CVD/CHD, with euthyroid state as reference. The mean age (SD) of the participants was 46.5 (12.0) years. At baseline, no significant difference was observed in the frequency of prevalent CVD cases (n=201) between all groups. No significant interaction was found between prevalent CVD and different thyroid function states with outcomes, hence, we did not exclude participants with prevalent CVD from data analysis. A total of 400 CVD events (358 CHD cases) during a median follow-up of 11.2 years (inter-quartile range: 1.96) occurred. During the follow-up, even in the age and sex adjusted model, no association was observed between different states of thyroid dysfunction and incidence of CVD/CHD. The multivariable hazard ratios (95% CI) of subclinical hypothyroidism, hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism for CVD events were 1.21 (0.77-1.88), 0.76 (0.33-1.69), 0.81 (0.46-1.41) and 1.48 (0.70-3.16), respectively. Both at baseline and during follow-up, no relation was observed between different states of thyroid function with prevalence and incidence of CVD/CHD.

Secondary and tertiary preventions of thyroid disease.

INTRODUCTION: Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impact of illness. METHODS: All articles related to secondary and tertiary prevention of thyroid diseases were reviewed. Using related key words, articles published between 2001 and 2015 were evaluated, categorized, and analyzed. RESULTS: In secondary prevention, congenital hypothyroidism and subclinical hypo and hyperthyroidism are equally important. Routine screening of patients with multinodular goiter by either ultrasonography or calcitonin is a controversial issue, while calcitonin assessments in medullary cancer and RET in family members are recommended. Screening of thyroid disease in pregnancy is limited to those with risk factors. Views regarding the importance of thyroid autoimmunity in secondary prevention are also presented. In tertiary prevention, prescribing excessive doses of levothyroxine, in the elderly in particular and appropriate care of all patients to avoid progression and complications are the key issues. CONCLUSION: Optimization of management of thyroid diseases requires timely screening, prevention of progression to more sever disease, optimal medical care, and avoidance of iatrogenic conditions.

The predictive value of metabolic syndrome for cardiovascular and all-cause mortality: Tehran Lipid and Glucose Study.

INTRODUCTION: The association of total and cardiovascular disease (CVD) mortality with metabolic syndrome (Mets) is controversial. We estimated the predictive value of MetS and its components for total and CVD mortality. MATERIALS AND METHODS: A total of 7932 subjects aged ≥ 30 years; participants of the Tehran Lipid and Glucose Study were enrolled and followed for 9.0 ± 2.3 years. MetS was defined according to three different definitions: World Health Organization (WHO), International Diabetes Federation (IDF) and Joint Interim Statement (JIS). RESULTS: WHO-MetS remained a significant predictor of total and CVD mortality in men (HR 1.66, 95%CI 1.23-2.24, p < 0.001; 1.93 HR 1.93, 95%CI 1.26-2.94, p = 0.002) and women (HR 2.01, 95%CI 1.39-2.88, p < 0.001; HR 2.71, 95%CI 1.44-5.09, p = 0.002), respectively. IDF-MetS was associated with increased risk of total mortality only in women (HR 1.51, 95%CI 1.07-2.12, p = 0.01), but after controlling for diabetes, IDF and WHO-MetS lost their associations. The incidence of CVD mortality was highest in WHO group (13.4) compared with IDF (8.5), JIS (8.14) and control (5.5) groups. The incidence of total mortality for WHO (27.1) was highest compared with IDF (17.7), JIS (16.5) and control (12.9) groups. In men, hypertension, impaired fasting glucose (IFG) and abdominal obesity and in women, IFG (WHO criteria) and high triglycerides levels increased the risk of CVD mortality. In men, hypertension and IFG directly and high triglycerides inversely were associated with total mortality. In women, IFG and obesity increased the risk of all-cause mortality. CONCLUSION: Diagnosis of MetS seems no more informative than its individual components in predicting mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Association between Thyroid Function and Body Mass Index: A 10-Year Follow-Up.

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 anti-thyroid 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.

Screening and management of hypothyroidism in pregnancy: results of an Asian survey.

Maternal hypothyroidism in pregnancy is associated with several adverse outcomes. The American Thyroid Association and the Endocrine Society Guidelines for the management of thyroid diseases in pregnancy were published in 2011 and 2012, respectively; however, impact of the guidelines in routine clinical practice is unknown. We therefore carried out a survey to study current practices in the screening and management of hypothyroidism in pregnancy. We collected completed questionnaire survey based on clinical case scenarios from 321 members of the Asia-Oceania Thyrpid Association (AOTA). Responses from 310 clinician members (from 21 Asian countries) were analyzed. For a woman with hypothyroidism planning pregnancy, 54% favored testing thyroid function before adjusting the dose, whilst 32% recommended increasing the dose of L-thyroxine (L-T4) as soon as pregnancy is confirmed. For a pregnant woman with newly diagnosed overt hypothyroidism, most responders initiated a full dose of L-T4. One half of responders used serum TSH and free T4 to monitor the dose of L-T4. Although the target of thyroid function tests that responders aimed to achieve with L-T4 was inconsistent, but a majority aim to keep TSH within recommended trimester specific range. Twenty-one % responders or their institutions screened all pregnant women for thyroid dysfunction, 66% performed targeted screening of only the high-risk group, whilst 13% did not carry out systemic screening. Majority of responders practices within recommendations of major professional societies; however, there is wide variation in the clinical practice in the treatment and screening of hypothyroidism during pregnancy in Asia.

Management of hyperthyroidism during pregnancy in Asia.

Maternal hyperthyroidism in pregnancy is associated with adverse impacts on both mother and fetus. Recently, the American Thyroid Association and the Endocrine Society have published guidelines for the management of thyroid diseases in pregnancy. We aimed to disclose the impact of these guidelines in current practices of Asian members of the Asia-Oceania Thyroid Association (AOTA) regarding the management of hyperthyroidism in pregnancy. Completed questionnaire survey, based on clinical case scenarios, was collected from 321 Asian physician members of AOTA from 21 Asian countries in 2013. For a woman with Graves' disease planning pregnancy, 92% of clinicians favored antithyroid treatment, 52% with propylthiouracil (PTU) while 40% preferred methimazole (MMI). For a pregnant woman with newly diagnosed overt hyperthyroidism, nearly all responders initiated PTU treatment. To monitor dosage of antithyroid drugs, approximately 73% of responders used TSH and free T4 (FT4) levels without free T3 (FT3) (53%) or with FT3 (20%). Majority of responders targeted achieving low serum TSH with FT4 (or total T4) in the upper end of the normal range. For management of gestational thyrotoxicosis, 40% chose to follow up and 52% treated patients with PTU. Although timing of TSH receptor antibodies measurement in pregnant hyperthyroid patients was variable, 53% of responders would check it at least once during pregnancy. Nearly 80% of responders do not treat subclinical hyperthyroidism in pregnancy. Therefore, despite wide variations in the management of hyperthyroidism during pregnancy in Asia, majority of Asian physicians practice within the recommendations of major professional societies.

The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

Aim: We 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. Method: Participants 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. Results: A 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. Conclusion: High 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.