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Purpose: There is limited research on the effects of maternal hyperandrogenism (MHA) on cardiometabolic risk factors in male offspring. We aimed to compare the risk of metabolic syndrome (MetS) in sons of women with preconceptional hyperandrogenism (HA) to those of non-HA women in later life., Methods: Using data obtained from the Tehran Lipid and Glucose Cohort Study, with an average of 20 years follow-up, 1913 sons were divided into two groups based on their MHA status, sons with MHA (n = 523) and sons without MHA (controls n = 1390). The study groups were monitored from the baseline until either the incidence of events, censoring, or the end of the study period, depending on which occurred first. Age-scaled unadjusted and adjusted Cox regression models were utilized to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in their sons., Results: There was no significant association between MHA and HR of MetS in sons with MHA compared to controls, even after adjustment (unadjusted HR (95% CI) 0.94 (0.80-1.11), P = 0.5) and (adjusted HR (95% CI) 0.98 (0.81-1.18), P = 0.8). Sons with MHA showed a HR of 1.35 for developing high fasting blood sugar compared to controls (unadjusted HR (95% CI) 1.35 (1.01-1.81), P = 0.04), however, after adjustment this association did not remain significant (adjusted HR (95% CI) 1.25 (0.90-1.74), P = 0.1)., Conclusion: The results suggest that preconceptional MHA doesn't increase the risk of developing MetS in sons in later life. According to this suggestion, preconceptional MHA may not have long-term metabolic consequences in male offspring., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: To investigate the association between estimated glomerular filtration rate (eGFR) change and mortality risk in a cohort from the Middle East and North Africa region with increasing chronic kidney disease burden., Methods: We included 2210 participants aged ≥ 50 years from the prospective cohort of the Tehran Lipid and Glucose Study. The interval for eGFR measurement was between the examinations in 2002-2005 to 2009-2011, and participants were followed through March 2018. Glomerular filtration rate was estimated from serum creatinine using the CKD-EPI creatinine equation. We assessed the association of rapid kidney function decline, (defined as annual eGFR decline ≥ 3 ml/min/1.73 m 2 per year); ≥ 30% eGFR decline over six years; and certain drop in kidney function (≥ 25% eGFR decline plus drop in eGFR category) with mortality outcomes., Results: During a median follow-up of 14.3 years after recruitment, 315 all-cause and 112 cardiovascular disease deaths were recorded. The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death for rapid kidney function decline, ≥ 30% decline in eGFR over 6 years, and drop in kidney function were 1.68 (1.24-2.27), 2.01 (1.46-2.78), and 1.49 (1.11-1.98), respectively. The HRs of all-cause death and for rapid kidney function decline in those without and with chronic kidney disease were 1.41 (1.03-1.91) and 3.38 (1.69-6.76), respectively. Similar findings were observed regarding cardiovascular disease-related and non-cardiovascular disease-related mortality., Conclusions: Estimated GFR decline is associated with an increased mortality risk, indicating its ability to provide additional prognostic information beyond traditional risk predictors in the general population., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Purpose: Prenatal androgen exposure could be a source of early programming, leading to the development of cardiometabolic diseases in later life. In this study, we aimed to examine cardiometabolic disturbances in males exposed to maternal androgen excess during their prenatal life., Methods: In this prospective population-based study, 409 male offspring with maternal hyperandrogenism (MHA), and 954 male offspring without MHA, as controls, were included. Both groups of male offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. Age-scaled unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association between MHA with pre-diabetes mellitus (Pre-DM), type 2 diabetes mellitus (T2DM), pre-hypertension (Pre-HTN), hypertension (HTN), dyslipidemia, overweight, and obesity in the offspring of both groups. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05., Results: A higher risk of Pre-DM (adjusted HR: 1.46 (1.20, 1.78)) was observed in male offspring with MHA after adjustment for potential confounders, including body mass index, education, and physical activity. However, no significant differences were observed in the risk of T2DM, Pre-HTN, HTN, dyslipidemia, overweight, and obesity in males with MHA compared to controls in both the unadjusted and adjusted models., Conclusion: Maternal androgen excess increases the risk of Pre-DM in male offspring in later life. More longitudinal studies with long enough follow-up are needed to clarify the effects of MHA on the cardiometabolic risk factors of male offspring in later life., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Anti-mullerian hormone (AMH) concentration is a marker of ovarian reserve that decreases with age. However, a decrease in AMH may occur more rapidly under the influence of environmental factors. The present study investigated the association between long-term exposure to ambient air pollutants with serum concentrations of AMH and the AMH rate of decline. This study included 806 women with median age of 43 years (interquartile range: 38-48) participating in the Tehran Lipid and Glucose Study (TLGS) that were followed from 2005 to 2017. The AMH concentration and the demographic, anthropometric, and personal health parameters of the study participants were obtained from the TLGS cohort database. Air pollutant data were collected from the monitoring stations and the individual exposures were estimated by previously developed land use regression (LUR) models. Multiple linear regression analysis was used to estimate linear relationships between the air pollutant exposures and serum concentration of AMH and with the AMH declination rate. The results show no statistically significant associations between exposures to any of the air pollutants (including PM 10 , PM 2.5 , SO 2 , NO, NO 2 , NO X , and benzene, toluene, ethylbenzene, p-xylene, m-xylene, o-xylene (BTEX), and total BTEX) with serum concentration of AMH. Compared to the first tertile, no statistically significant associations were observed between the second or third tertiles of air pollutants, with the AMH rate of decline. In this study, we did not find significant association between air pollution and AMH in middle age women in Tehran, Iran. Future work may study such associations in younger women., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Blood pressure (BP) is influenced by both individual and environmental factors such as ambient temperature. However, the gender-stratified and component-specific impact of temperature on BP is not well understood. Herein, we examined the temperature and seasonal effects on four main BP components, namely systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), in both genders. A total of 8990 (3954 men) Tehranian adults during 2015-2018 were included. Linear regression models for analyzing data in three models including unadjusted, age-adjusted, and further adjusted for known sociodemographic and cardiovascular confounders were conducted. Among women, each 10 °C increment was associated with a significant decrease of - 0.48 mmHg (95% confidence interval (CI): - 0.86, - 0.19) and - 0.65 mmHg (- 0.76, - 0.41) in SBP and MAP, respectively. In men, the corresponding value for SBP was - 0.46 (- 0.82, - 0.16) mmHg (P = 0.058). Gender-specific analysis in each season showed that among women, PP increased in autumn and winter with each 10 °C decrease (P < 0.05). The mean increase in SBP (3.4 and 2.06 mmHg in women and men, respectively), DBP (1.66 and 1.19 mmHg), and MAP (2.71 and 1.12 mmHg) was observed during winter compared to summer (all P < 0.05). PP showed seasonality only in women (1.46 mmHg, P-value = 0.003). In both genders, SBP in age > 60 years was more susceptible to variation compared to younger ages. Furthermore, obese women had more SBP changes compared to their non-obese counterparts (all P for interaction < 0.05). In conclusion, there was a sex difference in BP response to the outdoor temperature, with higher vulnerability among women. The reverse relation between temperature and BP occurred particularly among elderly and obese individuals. Careful monitoring of BP in cold seasons, specifically in the mentioned subgroups, could potentially attenuate cardiovascular risks., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To examine the associations between long-term exposure to five major air pollutants including SO 2 , PM 10 , O 3 , NO 2 , and CO , and incident dysglycemia, impaired fasting glucose (IFG), and diabetes, separately. A total of 4254 (1720 men) normoglycemic individuals aged 20-69 years at baseline were followed from 2001 to 2018 every 3 years. To measure the long-term hazards of air pollutants for incident dysglycemia, the Weibull proportional hazards models for every 10-unit increment adjusted for diabetes risk factors were fitted. The air pollutants were put in the models in the form of averages of 1-, 2-, and 3-year periods. During a median follow-up of 12.2 years, we observed 1780 dysglycemia events. In contrast to NO 2 , the increase in SO 2 , O 3 , and PM 10 levels were significantly associated with a higher risk of dysglycemia and IFG in all time spans excluding PM 10 at 2 years. The largest hazard ratios for incident dysglycemia and IFG were attributable to PM 10 in 3 years (2.20 (95% CI 1.67, 2.89) and 2.08 (1.55, 2.80), respectively). Moreover, exposure to all the pollutants except NO 2 in 1 year (0.89 (0.80, 0.98)) had no significant associations with incident diabetes. There was a signal that younger (< 45 years) and never-smoker individuals were more predispose to dysglycemic effects of air pollution (all P for interactions > 0.03). Our findings suggested that long-term exposure to air pollution increased incident dysglycemia risk, the effect which was mainly attributable to IFG status., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Controversies exist in the effect of body weight loss and fluctuation on cardiovascular disease (CVD) and mortality. This study aims to assess the effect of weight variability on CVD and all-cause and cardiovascular mortality in the Tehran Lipid and Glucose Study (TLGS) cohort., Method: Participants aged  ≥ 40 year at the baseline period with at least 3 BMI measurements were included in this study. After excluding individuals with cancer, CVD, end-stage renal disease, systemic use of glucocorticoids, pregnancy, and missing covariates at the baseline, a total of 3461 participants were enrolled and followed for 18 years. BMI variability was defined using root mean squared error (RMSE) and average successive variability (ASV). In the RMSE method, BMI variability was calculated using the best-fitting model for BMI trend of each subject. Multivariate Cox proportional hazard models were applied to assess BMI variability's effect on CVD and mortality., Results: Among the 3461 participants in this study, the group with the highest weight variability had an increased risk of death for all-cause (HR 1.65; 95% CI 1.21-2.25), non-cardiovascular (HR 1.77; 95% CI 1.24-2.53), and non-cancer (HR 1.77; 95% CI 1.25-2.50) mortality. However, BMI variability showed to be protective against CVD (HR 0.76; 95% CI 0.6-0.97). These findings were significant in males, non-smokers, participants with age  ≤ 60 year, BMI < 30, negative BMI slope, and both diabetic and non-diabetic subjects., Conclusion: High BMI variability is associated with increased risk of all-cause, non-CVD, and non-cancer mortality, although protective for the CVD event. Appropriate strategies for body weight maintenance after weight loss could be adopted to avoid weight variability, particularly in non-obese subjects., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: The significance of subclinical hypothyroidism (SCH) is largely due to its potential risk for developing overt hypothyroidism (OH). Investigations are still exploring predictive factors contributing to the progression of SCH to OH, particularly in patients with mildly elevated serum thyrotropin (TSH). We aimed to clarify the natural history of SCH and the predictive factors of its progression, based on the grade of SCH severity., Methods: This study was conducted within the framework of the Tehran Thyroid Study (TTS), in which 5783 individuals aged ≥ 20 years were followed. After applying exclusion criteria, data of 270 SCH subjects remained for the analysis. Thyroid function tests were assessed at baseline and every 3 years., Results: Of 270 participants with SCH, 239 (88.5%) had TSH level between 5.06 and 10 mU/L, and 31 (11.4%) had TSH ≥ 10 mU/L. During a median follow-up of 10 years, 40% had TSH within the reference range, 44% maintained elevated TSH, and 16% had added low T4 to the elevated TSH. The annual incidence rate of progression to OH was 22.3 (16.5-101.9) per 1000 person-years [18 (12.6-25.6) for those with TSH 5.07-9.9 mU/L and 57.8 (22.8-101.9) for patients with TSH ≥ 10 mU/L per 1000 person-years (P = 0.001)]. After adjusting age, sex, body mass index (BMI), thyroid peroxidase antibody (TPOAb), and serum TSH, only TPOAb positivity (HR: 2.31; 95% CI 1.10-4.83, P = 0.026) and baseline TSH level ≥ 10 mU/L (HR: 5.14; 95% CI 2.14-12.3, P < 0.001) remained as predictors for development of OH. In patients with TSH 5.07-9.9 mU/L, TPOAb positivity was associated with an increased risk of OH (HR: 2.41; 95% CI 1.10-5.30, P = 0.027). However, in patients with TSH ≥ 10 mU/L, TPOAb positivity was not a predictor (P = 0.49)., Conclusion: TPOAb and not TSH are associated with the development of OH in individuals with serum TSH below 10 mU/L, and follow-up at regular intervals is recommended in TPOAb-positive individuals with TSH between 5 and 10 mU/L., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Purpose: Fat mass and obesity-associated (FTO) is considered the first locus associated with adiposity, a concerning health problem worldwide. Many studies have evaluated the relationship between the FTO variants and obesity susceptibility. While the strong association of FTO rs1421085 with the risk of obesity across populations was reported in different studies, some researchers found a lack of association of this variant with adiposity. This systematic review and meta-analysis aimed to assess the association between obesity and rs1421085 polymorphism., Methods: We systematically searched PubMed, Scopus, and Google Scholar up to June 2022 to find pertinent studies. To further assess this issue, we surveyed the probable association of rs1421085 with obesity development among Iranian adults using the logistic regression analysis, and the obtained results were used for doing meta-analysis. After selection, nine eligible studies were included in the meta-analysis through the random- and fixed-effect models to determine the combined odds ratios (OR) and 95% confidence intervals (CI)., Results: According to our meta-analysis conducted on 5169 obese and 7772 non-obese individuals using different genetic models, including recessive, dominant, over-dominant, and additive, rs1421085 could positively increase the risk of obesity under all tested genetic models. Also, we detected a high to moderate level of heterogeneity among different studies under various genetic models., Conclusion: This meta-analysis further verified the positive association of FTO rs1421085 with the risk of developing obesity., Study Registration: This study is registered as PROSPERO CRD42021220092., Level of Evidence: Level I, systematic reviews and meta-analyses., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: This study aimed to compare the time to achieve euthyroidism and sustained control of hyperthyroidism after treatment with radioactive iodine (RAI) or long-term methimazole (LT-MMI) in patients with post-RAI relapsed hyperthyroidism., Methods: Sixty four patients with recurrence of hyperthyroidism after RAI treatment were randomly assigned to either RAI or LT-MMI treatment. Both groups were followed every 1-3 months in the first year and then every 6 months for a total of 60 months., Results: In RAI and LT-MMI groups, mean age was 49.0 ± 12.1 and 50.1 ± 14.6 years and time of relapse of hyperthyroidism after previous RAI treatment was 23.2 ± 18.8 and 20.8 ± 17.1 months, respectively. At the end of study, in the LT-MMI group, 31 (97%) and 1 (3%) were euthyroid and hypothyroid, respectively; in the RAI group, 8 (25%) patients were euthyroid, whereas 18 (56%), 3 (9.5%) and 3 (9.5%) had overt hypothyroidism, subclinical hypothyroidism and hyperthyroidism, respectively. Mean time to euthyroidism was 9.4 ± 5.0 months in the RAI group and 3.5 ± 2.8 months in the LT-MMI group (p < 0.001). Patients in the RAI group spent 77.7 ± 14.0 percent and those in the LT-MMI group spent 95.2 ± 5.9 percent of 60 months in the euthyroid state (p < 0.001)., Conclusion: In patients with post-RAI relapse of hyperthyroidism, LT-MMI treatment was superior to radioiodine because of faster achievement of euthyroidism and more sustained control of hyperthyroidism during 60 months of follow-up., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Purpose: To compare the effects of different thyroid screening scenarios, using the universal and targeted high-risk case-finding approaches with different diagnostic tests on the prevalence of subclinical hypothyroidism (SCH), thyroid autoimmunity, and pregnancy outcomes after adjustments for the intervention., Methods: During a secondary analysis of data collected in Tehran Thyroid and Pregnancy Study, a total of 2277 women from the total population, including 1303 high-risk individuals for thyroid dysfunction. The Cochran-Mantel-Haenszel method, adjusted for the intervention, was also used to evaluate the relationships between different screening scenarios [i.e., universal approach using thyroid-stimulating hormone (TSH) and/or thyroid peroxidase antibody (TPOAb) tests and targeted high-risk case-finding approach using TSH and/or TPOAb tests] and pregnancy outcomes (i.e., preterm delivery and NICU admission). The universal approach using both TSH and TPOAb measurements was considered as the reference scenario. We analyzed outcomes of different screening methods in individuals treated with LT4, compared to those individuals who were not treated., Results: Compared to the universal screening approach with both TSH and TPOAb measurements, the targeted high-risk case-finding approach overlooked approximately 42%, 62%, and 74% of women with elevated TSH (> 4 µlU/mL) when using both TSH and TPOAb tests, TSH alone, and TPO alone, respectively. After adjusting for the missed cases, 2.86% of women with preterm delivery and 2.76% of women with NICU admission were missed when they were screened using the targeted high-risk case-finding approach by measuring both TSH and TPOAb. The percentage of missed cases increased when applying the targeted approach with the TSH test alone, without measuring TPOAb. Overall, 4.16% and 4.02% of women with preterm delivery and NICU admission were overlooked in this scenario, respectively. After adjustments for the intervention, the probability of NICU admission in neonates of mothers, who were screened using the targeted high-risk case-finding approach with TPOAb measurement, was 2.31 folds higher than those screened by the reference scenario., Conclusion: This study suggests that although the targeted high-risk case-finding approach including both TSH and TPOAb tests, may overlook some women with SCH, it is a reasonable option since it is not associated with a higher risk of adverse pregnancy outcomes., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: Following the conventional 12-18 month antithyroid drug (ATD) treatment in Graves' disease (GD), 50% of patients experience relapse of hyperthyroidism., Objective: The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80 years., Methods: 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., Results: 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%., Conclusion: 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., (© 2021. Italian Society of Endocrinology (SIE).)

Anthracycline agents are routinely used for treatment of many types of malignancy, while imposing the risk for cardiotoxicity (AT-CMP). Although the right ventricle (RV) is more susceptible to cardiotoxicity, most of the studies have focused on left ventricle (LV) function for monitoring AT-CMP. In this study, we have focused on RV function before and after chemotherapy using two-dimensional speckle tracking Echocardiography. In this prospective study, newly diagnosed and untreated cancerous patients without previous cardiovascular diseases were enrolled. For all patients, baseline echocardiography was performed before the initiation of the anthracycline regimen and after 6 months of follow up when the chemotherapy was stopped. Several parameters of LV and RV function were measured using 3D echocardiography and STE techniques. 60 patients were enrolled in the study. There was a significant decrease (P = 0.001) in RV fractional area change (53.57% ± 4.36 vs. 45.66% ± 6.19), RV Global longitudinal strain (GLS) (- 22.93% ± 1.95 vs. - 18.53 ± 2.75), and RV free wall strain (FWLS) (- 25.75% ± 3.01 VS. - 20.30 ± 3.78). There was a significant decline in LVEF (59.42 ± 6.36% vs. 51.1 ± 6.31%) and LV-GLS (- 21.1 ± 1.8% vs - 18.6 ± 2.6%) (both P = 0.001) as well. Among the parameters changed following chemotherapy, RV-FWLS was dropped to a pathological level in 25% of patients showing the highest potential for detection of anthracyclines effect on the myocardium. Anthracycline therapy can induce subclinical RV dysfunction. In this clinical setting, RV free wall strain shows a great ability to exhibit deleterious effects of anthracyclines on the myocardium. This finding needs to be confirmed in future and larger studies., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: 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., Method: Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021., Results: 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., Conclusion: 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., (© 2021. Italian Society of Endocrinology (SIE).)

There are several treatment options for localized prostate cancer with very similar outcome but vary in terms of technique and side effect profiles and risks. Considering the potential difficulty in choosing the best treatment, a patient decision aid (PDA) is used to help patients in their decision-making process. However, the use and applicability of PDA in a country in Asia Pacific region like Malaysia is still unknown. This study aims to evaluate the effectiveness of a PDA modified to the local context in improving patients' knowledge, decisional conflict, and preparation for decision making among men with localized prostate cancer. Sixty patients with localized prostate cancer were randomly assigned to control and intervention groups. A self-administered questionnaire, which evaluate the knowledge on prostate cancer (23 items), decisional conflict (10 items) and preparation for decision-making (10 items), was given to all participants at pre- and post-intervention. Data were analyzed using independent T test and paired T test. The intervention group showed significant improvement in knowledge (p = 0.02) and decisional conflict (p = 0.01) from baseline. However, when compared between the control and intervention groups, there were no significant differences at baseline and post-intervention on knowledge, decisional conflict and preparation for decision-making. A PDA on treatment options of localized prostate cancer modified to the local context in an Asia Pacific country improved patients' knowledge and decisional conflict but did not have significant impact on the preparation for decision-making. The study was also registered under the Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12614000668606 registered on 25/06/2014., (© 2020. American Association for Cancer Education.)

Purpose: Aging is associated with significant changes in fat distribution and menopause may alter this process. This study aimed to investigate the longitudinal effect of menopause on changes in adiposity indices (AI)., Methods: A total number of 3876 non-menopausal women, aged > 20 years, who participated in the Tehran Lipid and Glucose study, were selected for the present study. They were followed from 1998 to 2018 at a 3-year interval and their adiposity indices were measured. Throughout the study, participants were categorized into two groups according to their menopausal status as group 1): women who reached menopause and group 2): women who did not reach menopause. The generalized estimation equation (GEE) models were used to compare the trend of changes in AIs between these two groups., Results: At the end of the study, a total number of 1479 (38.2%) participants reached menopause. The odds of general obesity decreased by 5% (OR: 0.95, 95% CI: 0.90-0.99), and the odds of central obesity increased by 6% in group1 compared to group2 (OR: 1.06, 95% CI: 1.01-1.12)., Conclusions: Menopause alters the impact of aging on central fat distribution. Increasing awareness of the related risk in menopausal women and their healthcare professional may prevent adverse related outcomes., (© 2021. Italian Society of Endocrinology (SIE).)

Background: Although Iran has been considered iodine replete since 2000, the first national survey of iodine intake among Iranian pregnant women in 2014 indicated that despite the adequate intake of iodine by the general population, this vulnerable group has moderate iodine deficiency. Therefore, in this national cross-sectional interventional study, we aimed to assess the iodine intake and thyroid function of Iranian pregnant women 2 years after implementing national iodine supplementation for this vulnerable group., Materials and Methods: In this cross-sectional study, we conducted a national interventional survey of pregnant women. A total of 1200 pregnant women (400 women from each trimester) from 12 provinces of Iran were recruited from the antenatal care clinics from October 2018 to March 2019. The median urinary iodine concentration (MUIC), as an indicator of iodine status in three spot urine samples, was measured, along with the serum total T4 (TT4), thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPO-Ab), and iodine content of household salt., Results: The mean age of the cohort was 28 ± 6.2 years, with the mean gestational age of 22.7 ± 13.0 weeks. The overall MUIC (IQR) of pregnant women was 188 µg/L (124.2-263 µg/L). Also, the MUICs in the three trimesters of pregnancy were 174 µg/L (110-254), 175 µg/L (116-251), and 165 µg/L (114-235), respectively. The MUICs ≥ 150, 100-149, and < 100 µg/L were found in 63, 19.8, and 16.2% of the subjects, respectively. The mean TT4 level was 12 ± 4.5 µg/dL, and the median (IQR) level of TSH was 2.37 mIU/L (1.66-3.18 mIU/L). According to our local reference range, 118 (10.5%) pregnant women had subclinical hypothyroidism, 6 (0.53%) women had isolated hypothyroxinemia, and 65 (5.7%) women were TPO-Ab positive. Also, the median (IQR) level of Tg was 10.08 µg/dL (5.7-20.4 µg/dL), and the median iodine content of household salt was 29.6 µg/g; the iodine content was ≥ 30 µg/g in 85% of household salt. The results showed that more than 95% of households were under iodized salt coverage., Conclusion: The results of this study indicated that iodine supplementation with at least 150 µg of iodine per day improved the iodine intake of pregnant women. Except for subclinical hypothyroidism, the prevalence of clinical hypothyroidism, clinical/subclinical thyrotoxicosis, TPO-Ab positivity, and isolated hypothyroxinemia decreased significantly, which emphasizes the importance of iodine supplementation during pregnancy., (© 2021. Italian Society of Endocrinology (SIE).)

Background: Preterm delivery (PTD) may predict the risk of long-term maternal complications. Little is known about the association between preterm delivery and maternal risk of chronic kidney disease (CKD).This study aimed to explore whether a history of preterm delivery is associated with the risk of maternal CKD., Methods: In this population-based cohort study within the framework of the Tehran Lipid and Glucose Study (TLGS), a total of 3035 women with at least one delivery met our eligibility criteria. A time-dependent Cox proportional-hazards regression model was used to measure the hazard ratios (HRs) and 95% confidence intervals (CIs) for evaluating the association between history of preterm delivery and risk of CKD, adjusted for smoking, parity, age at first delivery, body mass index, educational level, preeclampsia, and gestational diabetes mellitus., Results: A total of 212 women with a history of at least one preterm delivery and 2823 women with term delivery were included. The median (interquartile range) follow-up in the preterm and term delivery groups was 16 (13.0-17.0) and 16 (14.0-17.0) years, respectively. The results of multivariate Cox regression model, adjusted for confounders, showed that the risk of CKD significantly increased by 46% in women with a history of preterm delivery. Moreover, according to the time-dependent Cox regression analysis, the risk of CKD in women with a history of preterm delivery was 2.68 (95% CI 1.02, 7.05, P = 0.04) fold higher than among those with no history of  preterm delivery., Conclusion: Pregnancy if complicated by preterm delivery, may increase the risk of future maternal morbidities. Our findings suggest that a history of preterm delivery was associated with an increased maternal risk of CKD in the long term. Further longitudinal studies are needed to confirm our findings., (© 2021. Italian Society of Nephrology.)

Background: Lipid accumulation product (LAP) and visceral adiposity index (VAI) are surrogates for visceral adiposity dysfunction. Our aim was to evaluate potential association of these two indices with the incidence of renal function decline., Methods: We included 6693 non-diabetic adults age ≥ 18 years, with estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m 2 , from the Tehran Lipid and Glucose Study 2002-2005 survey. Natural logarithmic transformation (Ln) was applied for LAP and VAI measures. The incidence of renal function decline, defined as eGFR < 60 ml/min/1.73 m 2 , was evaluated for each gender, across tertiles of Ln LAP, Ln VAI, body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR) and waist to hip ratio (WHR), using Cox-proportional hazard models., Results: Over a median 8.6 years of follow-up, 1670 new cases of renal function decline were identified (incidence rate 3.2%). After multivariable adjustment, the hazard ratios (HRs) with 95% CI across second and third tertiles of Ln LAP were 1.14 (0.86-1.50) and 1.33 (1.00-1.78) in men (P trend = 0.132); and 1.16 (0.90-1.50) and 1.24 (0.96-1.61) in women (P trend = 0.263), respectively. Multivariable adjusted HRs across second and third tertiles of Ln VAI were 1.40 (1.08-1.83) and 1.35 (1.02-1.78) in men (P trend = 0.031); and 0.93 (0.75-1.15) and 1.15 (0.93-1.41) in women (P trend = 0.072), respectively. HRs across tertiles of BMI, WC, WHtR and WHR were not significant for renal function decline among both genders in any adjustment models., Conclusion: Among the adiposity indices assessed in this study, VAI seems to be an independent predictor of renal function decline only in males.

Purpose: Idiopathic granulomatous mastitis is a rare relapsing benign inflammatory breast disease with unknown etiology. Its clinical features and imaging signs may mimic inflammatory breast cancer or some other inflammatory breast disease. This may interfere with correct and timely diagnosis and thus impose an additional burden on the costs of diagnosis and therapy, as well as patient anxiety. We aimed to characterize the imaging findings of this disease and introduce two new imaging signs., Materials and Methods: This prospective study examined 36 patients with imaging and a clinical diagnosis of mastitis granulomatosis who were untreated and then confirmed by pathology. Demographic information, clinical data, imaging findings, and signs were recorded., Results: The age range of the patients was 22-60 years with an average of 36 years. Most of the patients (78%) were at reproductive age. None of the patients had a family history of granulomatous mastitis. Most patients with granulomatous mastitis (89%) lived in regions with low socioeconomic status. For most patients, sonography indicated a heterogeneous hypoechoic mass with irregular shape and ill-defined margin (26 cases; 72.2%). Focal asymmetry (36%) and obscured mass (36%) were the most common mammographic findings. Two signs of duct ectasia containing secretion and high-flow pseudocyst appearance were described., Conclusion: Mammographic and ultrasound findings can highly suggest a diagnosis of granulomatous mastitis in an appropriate clinical context.

Background: Obesity is currently an international epidemic and metabolic derangements pose these individuals at greater risk for future morbidity and mortality. Genetics and environmental factors have undeniable effects and among genetic risk factors, FTO/CETP genes are important. The current study examines the interaction between obesity phenotypes and FTO/CETP SNPs and their effects on lipid profile changes., Materials and Methods: We selected 954 adult subjects from TCGS (47.9% male). Participants were stratified according to their BMI and presence of metabolic syndrome according to the Joint Interim Statement (JIS) definition. Nine selected polymorphisms from FTO/CETP genes were genotyped using Tetra ARMS-PCR method. After age and sex adjustment the interaction of 9 markers with lipid profiles among phenotypes were tested by PASW., Results: In three main groups, HDL&#95;C level had a strong significant association with CETP markers: (rs3764261, β(95% CI) - 0.48(- 0.61 to - 0.35), P = 1.0 × 10 -11 ), (rs1800775, β(95% CI) 0.5(0.36;0.65), P = 1.0 × 10 -6 ) and (rs1864163, β(95% CI) 0.3(0.16;0.43), P = 9.1 × 10 -5 ). This association was also seen in rs7202116 within the total population. In only unhealthy metabolic obese (MUHO) subgroups four new FTO markers (rs1421085, rs1121980, rs1558902 and rs8050136) (P value < 0.01) demonstrated significant association, even after lipid profile adjustment., Conclusion: In the present study, we investigated the association between obesity phenotypes and some variations in FTO/CETP genes for the first time. Our study showed that four markers in the first intron of the FTO gene should be the risk marker in MUHO participants., Level of Evidence: Level III, case-control study.

Continued low-dose MMI treatment for longer than 12-18 months may be considered in patients not in remission. However, ATDs are not free from adverse effects. We undertook a systematic review to clarify safety of long-term ATD treatment. Medline and the Cochrane Library for trials published between 1950 and Nov 2018 were systematically searched. We included original studies containing data for long-term (> 18 months) ATD treatment. Two reviewers independently extracted data from included trials and any disagreement was adjudicated by consensus. Of 615 related articles found, 12 fulfilled the criteria. Six articles had data for adults, five for non-adults and one article had data for both groups. The sample sizes ranged between 20 and 249 individuals, and the mean duration of ATD treatment ranged between 2.1 and 14.2 years. Considering all data from 1660 patients treated with ATD for a mean duration of 5.8 years (around 10,000 patient-years), major complications occurred only in 14 patients: 7 severe agranulocytosis, 5 severe liver damage, one ANCA-associated glomerulonephritis and one vasculitis with small cutaneous ulcerations. Minor complications rates were between 2 and 36%, while more complications were in higher doses and in the children. The most reported AE was cutaneous reaction; the other adverse events were elevated liver enzymes, leukocytopenia, arthritis, arthralgia, myalgia, thrombocytopenia, fever, nausea and oral aphthous. Long-term ATD treatment is safe, especially in low dose and in adults, indicating that it should be considered as an earnest alternative treatment for GD.

Background: Iodine deficiency and related disorders were very common in Iran prior to 1996, when universal salt iodization (USI) was implemented and in 2000 Iran was declared iodine deficiency disorders (IDD) free. The aim of this study was to evaluate the adequacy of iodine intake by Iranian households in all 30 provinces of Iran, a quarter of a century after the intervention., Methods: A total of 18,000 school-aged children (8-10 years with mean 8.7 ± 1 year) were included in this study. Urine samples were collected from all children for measurement of urinary iodine excretion and 1800, 210 and 3000 salt samples were randomly collected from the family kitchen, production site of 73 salt factories and distribution circles of 30 provinces, respectively., Results: The median urinary iodine concentration (UIC) of participants was 161 μg/L. The proportion of children with UIC of, 20-49, 50-99 and ≥ 100 μg/L were 10.3, 15.9 and 73.7%, respectively. The mean (± SD) and median salt iodine values were 28.2 (± 12.6) and 31.7 ppm, at the production site, and 31.5 (± 13.6) and 29.6 ppm at the distribution circles, respectively. About 80% of factory salts had more than 20 ppm iodine. 98% of households consumed iodized salt, 80% had appropriate salt storage, and 83% of the household salts contained ≥ 20 ppm., Conclusions: Based on the results of this study, Iranian populations are consuming adequate iodine. The well-maintained and monitored USI program has improved the dietary iodine intakes of the population, and the country has achieved all criteria of a well-controlled IDD program.

Purpose: This study aimed to investigate the interactive effect of polycystic ovary syndrome (PCOS) status and obesity status on the serum levels of adipokines., Methods: In this comparative case-control cross-sectional study, 58 women with PCOS and 104 eumenorrheic non-hirsute women as the control group were recruited. They were further divided into two subgroups of overweight/obese and normal weight. The interactive effect of the PCOS status and obesity status on the circulating levels of adipokines was assessed using general linear model with the adjustment of age., Results: A statistically significant negative interaction was reported between obesity status and PCOS status in the determination of serum adiponectin and resistin concentrations (effect size = -0.14, interaction P = 0.001, effect size = -0.15, P = 0.016). It indicated that adiponectin and resistin were significantly decreased in overweight/obese patients with PCOS compared with other subgroups. Statistically significant positive interactive effects were found between PCOS status obesity status and leptin (effect size = 0.321, interaction P = 0.036), indicating that the overweight/obese women with PCOS had the higher levels of leptin compared with the control group. Also, no interaction was reported between PCOS status and obesity status with regard to the serum levels of other adipokines., Conclusions: While no sufficient evidence is available with regard to the causal association between adipokines and PCOS, they may contribute to the development of PCOS and regarded as the novel biomarkers of PCOS.

Aim: To evaluate the relationship between inflammatory and pro inflammatory markers, with obesity and visceral adiposity in male subjects with or without metabolic syndrome (MS)., Subjects and Methods: A total of 37 patients with MS and 37 age matched controls were included (mean age 46.35 ± 1.6 years). MS was defined by the criteria of the international diabetes federation 2005. Anthropometric and biochemical profiles, including high-sensitivity C-reactive protein (Hs-CRP), visfatin and interleukin 6 (IL-6), were measured. Data were compared between groups by using t test. Pearson's correlation was used to evaluate the relationship between variables. P values less than 0.05 were considered as statistically significant., Results: In patients with MS, CRP and IL-6 were significantly correlated with body mass index, waist circumference and waist to hip ratio. Visfatin levels were significantly lower in patients with MS compared to controls (log visfatin: 1.74 ± 0.27 vs. 1.86 ± 0.13 ng/ml, MS vs. control group respectively). We cannot find any significant correlation between visfatin, CRP and IL-6. Also there were no correlation between visfatin levels and any anthropometric parameters in patients with MS or control groups., Conclusion: Serum visfatin was lower in patients with MS. Therefore it seems that visfatin could not be considered as a pro inflammatory adipocytokine in MS. The positive associations of obesity and visceral adiposity with elevated CRP and IL-6 levels suggest the importance of reducing visceral adiposity to prevent the risk of coronary disease.

Purpose: I. R. Iran has been considered iodine replete since 2000, but iodine nutrition of vulnerable subjects is not clear. The main goal of this study was assessment of iodine nutrition and thyroid function in pregnant Iranian women., Methods: A total of 1072 pregnant women from ten provinces in the different parts of the country were recruited from November to March 2014. Median urinary iodine concentration (UIC) as the measure of iodine status and serum free T4 (FT4), thyrotropin (TSH), thyroglobulin (Tg), anti-thyroglobulin and anti-thyroid peroxidase antibodies (TgAb and TPOAb) were measured., Results: Mean ± SD age of the cohort was 27.0 ± 7.2 years and gestational age was 20.7 ± 10.0 weeks. The median UIC for pregnant women was 87.3 μg/L, being 92.1, 86.0 and 76.8 μg/L, in three trimesters of pregnancy, respectively. Median UIC of <100, 100-149, 150-249, 250-499 and ≥500 μg/L was found in 58.4, 19.8, 16.2, 5.13 and 0.46 % of subjects, respectively. Median (IQR) values in the first, second, and third trimesters were 1.7 (0.9-2.8), 2.1 (1.5-2.9), and 2.1 (1.4-2.8) mIU/L for TSH, and 16.4 (12.21-21.13), 14.34 (12.16-19.69), and 14/07 (12.02-18.64) pmol/L for FT4, respectively. The frequency of elevated serum TSH was 9.0 % (6.6 % subclinical, 2.4 % overt hypothyroidism). The frequency of low serum TSH was 0.6 %. The frequency of positive TPOAb was 7.6 %., Conclusions: Results of this study have clarified that despite iodine sufficiency of school children in Iran, pregnant women have moderate iodine deficiency and need iodine supplementation.

Purpose: Wrist circumference is an easy to measure anthropometric index of body frame and bone size. The aim of this study was to examine the association of wrist circumference with incidence of cardiovascular disease (CVD) among adult men., Methods: For this study 2531 male participants aged ≥30 years, without any history of CVD were selected and followed from 1999 to 2011. Cox proportional hazard models and logistic regression were used to examine the relation of wrist circumference with incident CVD., Results: A total of 339 cases of CVD were reported throughout a median follow-up of 9.4 years. In the multi-variable Cox model, 1 unit increase of wrist circumference was inversely associated with incident CVD with a HR (95 % CI) of 0.84 (0.72-0.98, P value = 0.02). The receiver operating characteristics curve in a logistic regression model for wrist circumference in prediction of CVD showed a cutoff of 17.75 cm, beyond which was associated with a lower risk for CVD., Conclusion: In a population with a high prevalence of CVD risk factors, it was shown that a higher wrist circumference was associated with lower risk for incident CVD. Further studies are needed to explore the underlying mechanisms of this inverse relation.

Background: There is growing evidence of the potential properties of nitrate-rich foods against development of hypertension (HTN) and vascular disease. In this study, we investigated the association of nitrate-containing vegetables (NCVs) with risk of HTN after 3 years of follow-up., Methods: This prospective study was conducted on 1546 non-hypertensive subjects, aged 20-70 years. Blood pressure was measured at baseline and after 3 years and HTN was defined by the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure criteria. Dietary intake was collected using a validated semi-quantitative food frequency questionnaire (FFQ). NCVs and high-, medium- and low-NCV subcategories were defined, and the odds of HTN after 3 years according to tertiles of NCV and NCV-category intake were estimated by logistic regression and adjusted for potential variables., Results: Mean age of participants was 38.0 ± 12.0 years at baseline and 57.0 % were women. Mean dietary intake of energy-adjusted NCV was 298.0 ± 177.3 g/day. After adjustment for total energy intake, fiber, sodium, potassium and processed meat, a significant inverse association was observed between NCV and the risk of HTN in the highest tertile category (odds ratio 0.63, 95 % confidence interval: 0.41-0.98, p for trend = 0.05). There was no significant association of 3 year risk of HTN across tertiles of low nitrate-, medium nitrate- and high-nitrate vegetables., Conclusion: Higher dietary nitrate intake from vegetables sources may have a protective effect against development of HTN.

Purpose: There is much controversy regarding the use of oral contraceptive pills (OCPs) on cardiometabolic parameters, which is why this longitudinal population-based study was conducted to assess the impact of OCP use and its duration on cardiometabolic factors., Methods: Of 5532 reproductive-aged participants of the Tehran lipid and glucose study, 3160 women who met our inclusion criteria were subdivided according to the duration of OCPs consumption into four sub-groups: (1) Non-users; (2) <11 month users; (3) 12-35 month users, and (4) ≥36 month users, and their cardiometabolic parameters were compared., Results: No statistical significant differences were observed between the cardiometabolic parameters of these sub-groups, after further adjustment for confounding factors including age, parity, and education, except for mean low-density lipoprotein-cholesterol which was significantly higher in women who used OCPs for >36 months in comparison to non-OCP users. The odds ratio of hypercholesterolemia was significantly higher in women who used OCPs for >36 months in comparison to non-OCP users; being 1.5 times higher than non-users (95 % CI 1.01-2.2)., Conclusion: Results showed that if used for less than 3 years, OCPs have no cardiometabolic effects.

Purpose: Hirsutism is the most common indicator of hyperandrogenism. Both, the sensitivity of the patients to the serum androgen levels and the responsiveness of women to the perceived excess hair growth vary among different populations. This report elaborates the relationship between the woman's discerned abnormal hair growths with the clinical diagnosis of hirsutism., Methods: The survey was conducted among 1160 women aged 18-45 and randomly selected from Tehran Lipid and Glucose Study for further detailed assessment of Hirsutism; using the m-FG scoring method. Data gathering was performed by interviews and physical examinations. The receiver operating characteristic curve was drawn and the new cutoff value, sensitivity, specificity and concordance percentage were calculated., Results: The results demonstrated that among 12 androgen-dependent body areas, the chin skin had the highest area under curve of 0.81 (CI; 0.78-0.84). According to the patient's evaluation, a threshold point of 4 had the optimum concordance percentage of 0.77 with the modified Ferriman-Gallwey scoring system., Conclusions: Patient's self-identification of excess terminal hair based on the chin area has great sensitivity and reliability in predicting the clinical hirsutism.

Purpose: Menopausal status exposes women to increased risk of cardiovascular disease. This study was performed to compare the effect of menopausal types, including surgical and natural, on metabolic syndrome and other metabolic disorders 3 years before and after menopause., Methods: Of 437 postmenopausal women, who participated in the Tehran Lipid and Glucose Study, 13 women with surgical menopause and 39 age-matched controls with natural menopause were selected. During the follow-up period, changes in metabolic and biochemical profiles were compared between surgical and natural menopause women., Results: Odds of incidence of metabolic syndrome in surgical menopause women, compared to natural menopause women, was 9.7 (95 % CI 1.8-51.8)., Conclusions: Metabolic disturbances after menopause are highly influenced by type of menopause and are more prevalent in those undergoing surgical menopause.

Purpose: In our previous study, we introduced a rat model of polycystic ovary syndrome (PCOS) induced by prenatal exposure to a single dose of testosterone on embryonic day 20. In the current study, we aimed to investigate whether prenatal exposure to a single dose of testosterone could also induce metabolic disturbances, especially insulin resistance in adulthood (100-110 days of age) and also to make it as an appropriate rat model of PCOS (exhibiting both reproductive and metabolic disturbances with minimum morphological disorders in reproductive system) for further studies in PCOS., Methods: Pregnant rats in the experimental group were subcutaneously injected with 5 mg free testosterone on the gestational day 20, while controls received only the solvent. Female offspring of both groups, prenatally androgenized (PNA) rats (PCOS models of rats) and controls were examined., Results: Body weight measures showed significant increase in the PNA rats compared to controls on days 30, 45, 60 of age and in adulthood (P < 0.05). PNA rats showed insulin resistance compared to controls. Impaired glucose tolerance was not observed in the PNA rats compared to controls. There were no significant differences in lipid profile between the PNA and control rats (P > 0.05)., Conclusion: Our study suggests that metabolic disturbances in PCOS and their severity during adult life probably depend on the particular time and levels of prenatal androgen exposure.

Background: Although dietary components may play a role in the development of chronic kidney disease (CKD), data on this topic are scarce. The objective of this study was to investigate the association between macronutrient intakes and CKD in a large non-diabetic adult population-based study., Methods: This cross-sectional study recruited 5,316 participants aged ≥27 years without diabetes within the framework of the Tehran lipid and glucose study. Dietary intake was collected using a validated food-frequency questionnaire. Macronutrients intake including total-, animal-, and plant-protein, carbohydrate, simple sugar, fructose, total fat, saturated fatty acids, poly- and monounsaturated-fatty acids (PUFA and MUFA), and n-3 and n-6 fatty acids was categorized into quartiles. Anthropometrics, blood pressure, serum creatinine, and fasting plasma glucose and lipids were measured. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease Study equation. CKD was defined as eGFR <60 ml/min/1.73 m(2)., Result: Mean age of participants was 45.0 ± 12.2 years. Mean eGFR was 71.9 ± 11.1 ml/min/1.73 m(2), and 13% had CKD. After adjustment for serum triglycerides and cholesterol, body mass index, and hypertension, the risk of CKD decreased in the highest quartile compared to lowest quartile of plant protein (OR, 95% CI) (0.70, 0.51-0.97), PUFA (0.73, 0.55-0.99), and n-6 fatty acids (0.75, 0.57-0.97). However, the risk of CKD increased in the highest quartile of animal protein (1.37, 1.05-1.79) compared to the lowest., Conclusion: Plant protein, PUFA, and n-6 fatty acids are associated with a lower risk of CKD, independently of hypertension and diabetic mellitus, while animal protein may be a risk factor for CKD in adults.

Purpose: To evaluate the association of idiopathic hirsutism, insulin resistance and metabolic disorders., Methods: Participants of this study included 137 women with idiopathic hirsutism and 698 women as controls selected from two large population-based cross-sectional studies including 1,772 reproductive-aged women. Anthropometric and biochemical characteristics of the participants were measured and compared; for instance, insulin resistance was estimated through the homeostatic model assessment and the metabolic syndrome was detected using the Joint Interim Statement., Results: Mean age, body mass index and other anthropometric measures including waist and hip circumferences were statistically higher in women with idiopathic hirsutism. No differences were observed in blood pressure, glucose and lipid profiles, homeostatic model assessment or the prevalence of insulin resistance, obesity and metabolic syndrome in women with idiopathic hirsutism and controls after adjustment of age and body mass index. In the subgroup of women with metabolic syndrome, fasting glucose levels of those with idiopathic hirsutism were significantly higher than controls, after adjustment of age and body mass index as 114 ± 25.85 vs. 103.52 ± 41.90 mg/dL, P = 0.003. Furthermore, the age and body mass index-adjusted prevalence of impaired fasting glucose in women with idiopathic hirsutism were higher than controls as 16.8 vs. 4.6%, OR = 2.26, 95% CI 1.59-5.38. A threshold of 74.5 cm for waist circumference had the optimal combined sensitivity and specificity for prediction of insulin resistance in women with idiopathic hirsutism, though this value was 90.5 cm for controls., Conclusions: Our data suggest that although the overall metabolic characteristics were similar in women with idiopathic hirsutism and controls, glycemic disturbances were more often seen in those suffered from metabolic syndrome and idiopathic hirsutism simultaneously.

Laboratory experiments were carried out to study the effects of slow mixing conditions on magnesium hydroxide floc size and strength and to determine the turbidity and total suspended solid (TSS) removal efficiencies during coagulation of highly turbid suspensions. A highly turbid kaolin clay suspension (1,213 ± 36 nephelometric turbidity units (NTU)) was alkalized to pH 10.5 using a 5 M NaOH solution; liquid bittern (LB) equivalent to 536 mg/L of Mg(2+) was added as a coagulant, and the suspension was then subjected to previously optimized fast mixing conditions of 100 rpm and 60 s. Slow mixing speed (20, 30, 40, and 50 rpm) and time (10, 20, and 30 min) were then varied, while the temperature was maintained at 20.7 ± 1 °C. The standard practice for coagulation-flocculation jar test ASTM D2035-13 (2013) was followed in all experiments. Relative floc size was monitored using an optical measuring device, photometric dispersion analyzer (PDA 2000). Larger and more shear resistant flocs were obtained at 20 rpm for both 20- and 30-min slow mixing times; however, given the shorter duration for the former, the 20-min slow mixing time was considered to be more energy efficient. For slow mixing camp number (Gt) values in the range of 8,400-90,000, it was found that the mixing speed affected floc size and strength more than the time. Higher-turbidity removal efficiencies were achieved at 20 and 30 rpm, while TSS removal efficiency was higher for the 50-rpm slow mixing speed. Extended slow mixing time of 30 min yielded better turbidity and TSS removal efficiencies at the slower speeds.

Background: Current reference values for thyroid function tests are based on data from different ethnicities and geographical areas. The aim of the present study was to determine reference intervals for thyrotropin (TSH) and free T4 (FT4), based on the criteria of the National Academy of Clinical Biochemistry (NACB) in an Iranian population., Material and Methods: This study was conducted within the framework of Tehran Thyroid Study (TTS), an ongoing prospective cohort of 5704 randomly selected individuals, age ≥ 20 yr. A total of 2199 individuals (43.3% male, 56.7% female), based on NACB criteria were included in this study. Reference limit analysis was performed for the negative thyroid peroxidase antibody (TPOAb) group., Results: After applying all exclusion criteria except TPOAb positivity (10.5%), data of 2459 participants remained for analysis. Of these, 953 (43.3%) were males and 1246 (56.7%) were females; the mean ± SD age was 43.53 ± 14.16 yr. The mean ± SD and median+IQR for TSH were 1.77 mU/l ± 1.24 and 1.46 (0.93-2.23) mU/l, respectively. The 2.5th and 97.5th percentiles TSH were 0.32 mU/l and 5.06 mU/l respectively. The mean ± SD and median (IQR) for FT4 for all negative TPOAb subjects were 1.19 ± 0.16 and 1.18 (1.08-1.31) ng/dl respectively., Conclusion: Reference ranges for thyroid function tests need to be derived from national databases. This study determined age and sex specific TSH and FT4 reference ranges in a Tehranian population, which could eventually enable clinicians to classify patients more appropriately.

Background: Despite the high prevalence of thyroid dysfunction, the epidemiology and natural course of these disorders have not been identified yet., Aim: The present survey was conducted to determine the incidence of thyroid dysfunction and natural course of subclinical thyroid disorders in an urban community of Tehran, I.R. Iran., Subjects and Methods: Serum TSH and thyroperoxidase antibody (TPOAb) were measured at baseline and after 6.7 yr from a sample of 1999 randomly selected subjects aged≥20 yr, participants of the Tehran Lipid and Glucose Study (TLGS). Median TSH value and 2.5, 5, 95, and 97.5 TSH percentiles were determined at baseline using data obtained from 808 negative TPOAb subjects with no history of any thyroid disease or surgery, goiter, nodule, taking thyroid hormone preparations or anti-thyroid drugs. In those with abnormal TSH level, total T4 and T3 uptake were measured and free T4 index was calculated., Results: Normal TSH reference range was 0.4-5.8 μU/ml according to the 2.5 and 97.5 TSH percentiles. The incidence rates of thyroid function abnormalities in 1000 subjects per year were as follows: clinical hypothyroidism: 0.28 in women and 0.21 in men; subclinical hypothyroidism: 11.59 in women and 4.69 in men; clinical hyperthyroidism: 1.4 in women and 0.21 in men; and subclinical hyperthyroidism: 5.72 in women and 3.62 in men. A significant increase was found in the frequency of positive TPOAb in women from 15.9 to 17.7% (p=0.006). Of 8 women with subclinical hypothyroidism at baseline, 5 remained unchanged, 1 became normal, and 1 developed clinical hypothyroidism at followup. Two women with subclinical hyperthyroidism normalized at follow-up. Of 2 men with subclinical hypothyroidism at baseline, 1 remained unchanged, whereas the other progressed to clinical hypothyroidism., Conclusion: After a 6.7 yr follow-up significant increase in the incidence of subclinical thyroid disorders was observed in both men and women, as compared to overt thyroid dysfunction. Increase in the prevalence of TPOAb positivity was observed only in women.

Aim: To quantify the burden of cardiovascular diseases (CVD), and all-cause mortality attributable to diabetes., Subjects and Methods: Data on an 8.6-yr follow-up of 6331 participants (2741 men), free of CVD at baseline, were analyzed to determine the burden of CVD and all-cause mortality attributable to self-reported and screen-detected diabetes mellitus (SRDM and SDDM, respectively). Risks of events of interest were separately assessed for women and men using Cox-proportional-hazard model., Results: The mean age at baseline was 47 yr with 997 (15.7%) of participants having diabetes (men 14.8%, women 16.5%). SRDM and SDDM prevailed in 9.7% (men 9.2, women 10.2%) and 6.0% of participants (men 5.7, women 6.3%), respectively. During follow up (52,404 person-yr), we observed 447 incident cases of CVD [387 had coronary heart disease (CHD)] and 209 deaths. Among men, participants with SDDM had increased relative hazard for all-cause mortality translated to a population attributable risk fraction (PAF) of 10.1%. Among women, SDDM was associated with CVD and CHD but not with all-cause mortality; so that 9.3% and 8.8% of CVD and CHD events were respectively attributable to the SDDM. If SRDM had been eliminated from the population, the incidences of CVD, CHD, and death would have decreased by 10.5, 9.5, and 17.3% in men; and 22.0, 24.2, and 17.8% in women, respectively., Conclusion: SDDM and SRDM have high PAF for all-cause mortality and CVD. Besides diabetes treatment and prevention, screening to detect undiagnosed diabetes should warrant high priority among the public health strategies to lower the incidence of CVD and mortality.

Background: Iran has long been recognized as a country of iodine sufficiency; however, recent studies show that the proportion of subjects with insufficient urinary iodine is gradually increasing in Tehran capital city., Aim: The aim of this study was to evaluate differences between individuals with sufficient and deficient urinary iodine in Tehran., Material and Methods: In this cross-sectional study, 639 Tehranian adult subjects, aged ≥ 19 yr (242 males, 397 females), were enrolled through randomized cluster sampling. A 24-h urine sample was collected for measurement of urinary iodine, sodium and creatinine concentrations using the digestion method, flame photometry and autoanalyzer assay, respectively. Salt intake was estimated and iodine content of household salt was measured by titration., Results: Medians (interquartile range) of 24-h urinary iodine concentrations in subjects with sufficient and deficient urinary iodine were 163.0 (126.0-235.0) and 44.0 (26.0-67.0) μg/l, p<0.001, respectively. Salt with iodine content of >20 parts per million was consumed by 77.4 and 38.3% of subjects with sufficient and deficient urinary iodine, respectively (p<0.001). Median daily salt intake in subjects with sufficient urinary iodine was significantly higher than in those with deficient urinary iodine (8.1 vs 7.3 g, p<0.001). No significant differences in the mentioned variables were observed between males and females. Fifty and 30% of subjects with insufficient and sufficient urinary iodine had <7 yr education, respectively (p<0.001)., Conclusions: Iodine content of salt, the amount of salt intake and education levels differ greatly between subjects with sufficient and deficient urinary iodine in Tehran.

Objective: Thyroid hormone deficiency may affect human speech and voice. The aim of this study was to evaluate speech variables in patients with hypothyroidism., Design: A case control study., Patients: One hundred and twenty patients, 106 women and 14 men with symptoms and signs of thyroid failure; the diagnosis was confirmed by serum T4<4.5 μg/dl and serum TSH>10 mU/l. Eighty-eight normal subjects, 78 women and 10 men, age-, sex-, and smoking status- matched, served as controls., Measurements: All symptoms and signs of hypothyroidism were recorded. Serum T4, T3, and TSH concentrations were measured. Speech parameters were analyzed by the Visipitch III system model 3900 and multidimensional voice program software and compared to a group of normal subjects with no thyroid disease., Results: Mean age was 35.9±11.4 yr. Dryness in larynx and pharynx, dyspnea, and sensation of lump in the throat were reported by 53.49 and 43% of patients, respectively. Fundamental frequency, voice turbulence index, and soft phonation index were significantly different from control values. There was positive correlation between TSH concentration and variation in fundamental frequency and prevalence of voice disorders (37.2±31.2 vs 23.9±25.8 mU/l, p<0.003)., Conclusion: Frequent speech disturbances occur in patients with primary hypothyroidism.

Background: Iodine deficiency constitutes a public health problem in many countries worldwide. Fetal neurodevelopment is affected by maternal iodine intake. The aim of present study was to assess urinary iodine excretion (UIE) in the 3 trimesters of pregnancy and evaluate its association with newborn thyroid function in Tehran, an area of iodine sufficiency., Methods: Based on median urinary iodine in 3 trimesters, 138 pregnant women were divided into 2 groups with UIE<150 (group I) and UIE ≥ 150 μg/l (group II). Cord blood samples of their newborns were evaluated for serum concentrations of TSH, T3, T4, free T4 (FT4), and thyroglobolin. Quartiles of UIE were also determined. Correlations between mothers' UIE and newborns' thyroid function in both groups were investigated., Results: Fifty-two pregnant women (38%) had median UIE<150 μg/l and 86 had (62%) UIE ≥ 150 μg/l. Median UIE in groups I and II in the 1st, 2nd, and 3rd trimesters were 125 and 212 μg/l, 97 and 213 μg/l, 93 and 227 μg/l, respectively. No significant difference was seen in thyroid function of newborns in the 2 groups. Mean concentrations of T4, T3, FT4, and TSH of newborn did not show significant difference in median UIE of mothers in various quartiles., Conclusion: This study shows that newborns, irrespective of mothers' UIE, in an area with a sustained iodine supplementation program, may not be at risk of alterations in thyroid functions.

Background: Despite the high prevalence of diabetes, limited information is available about the impact of impaired glucose regulation on the cardiovascular disease (CVD) risk among Middle East populations., Aims: To determine the risk of CVD in an urban Iranian population according to glucose tolerance status., Materials and Methods: The study population consisted of 1752 men and 2273 women, aged > or = 40 yr, free of CVD at baseline. Incident CVD was ascertained over a median of 7.6 yr of follow-up., Results: A total of 340 CVD events occurred (197 in men and 143 in women). At baseline, there was no difference between newly diagnosed and known diabetes regarding the Prospective Cardiovascular Münster (PROCAM) risk score and prevalence of metabolic syndrome in both genders. Applying the 1997 American Diabetes Association (ADA) criteria, compared with those with normal glucose tolerance, after controlling traditional risk factors, hazard ratios (HR) and 95% confidence intervals (95% CI) for CVD in women with known and newly diagnosed diabetes were 3.30 (2.09-5.21) and 1.93 (1.16-3.21) and the corresponding values for men were 1.90 (1.11-3.25) and 1.69 (1.12-2.54), respectively. Impaired fasting glucose or impaired glucose tolerance was associated with 56% increased risk of CVD in women (HR 1.56, 95% CI 1.00 to 2.45), in the age-adjusted analysis, considering the 2003 ADA criteria., Conclusions: All diabetic subjects, whether newly diagnosed or known cases, should receive intensive primary prevention for CVD regardless of risk factors, in particular females with abnormal glucose regulation.

Background: Changes in concentration of thyroid hormones can affect Na+-K+-ATPase number and activity and phospholipid composition of the cell membranes leading to changes in the surface to volume ratio and strength of membrane., Aim: In this study, the osmotic fragility of the red blood cells from non-treated hypo- and hyperthyroid patients was compared to that of control subjects., Material/subjects and Methods: After 3 washings with normal saline, red blood cells were placed in varying concentrations of sodium chloride (Na- Cl) (0-0.9%) and fragility was assessed with colorimetric method; to do this, after the incubation period, tubes were centrifuged and the optical density of the tubes was measured. Hemolysis percentage in tubes was calculated based on 100% hemolysis in the tubes containing no NaCl (0%)., Results: Osmotic fragility of the cells from hyperthyroid patients in 0.45% NaCl was significantly lower than control subjects (74.6%+/-30.2 vs 93.8%+/-9.1, p<0.01). The osmotic fragility of red blood cells in 0.5% concentration of sodium chloride in hyperthyroid patients was significantly lower compared to that of controls (27.8%+/-26.0 vs 63.5%+/-27.5, p<0.001). No significant difference was observed between the osmotic fragility of the hypothyroid patients compared with control subjects., Conclusions: Alteration in osmotic fragility is seen in patients with hyperthyroidism; however, anemia reported in hypo- or hyperthyroid patients is not due to high osmotic fragility of red blood cells and other causes need to be investigated.

Objective: Two yr after legislation of salt iodization of 40 parts per million (ppm) in 1994, goiter was still endemic and urinary iodine concentration (UIC) remained elevated in many provinces of Iran. Goiter prevalence and UIC were compared 2 and 7 yr after sustained consumption of uniformly iodized salt by Iranian households., Methods: Schoolchildren (7-10 yr) of all provinces were randomly selected by cluster sampling from December 2000 to June 2001. Goiter rate, UIC, and household salt iodine values were compared to those in 1996. Factory salt iodine was also compared in 2001 vs 1996. Ultrasonographically determined thyroid volumes of 7-10 yr old children were compared in 2001 vs 1999., Results: In 2001 (no.=33600) vs 1996 (no.=36178), total, grade 1, and grade 2 goiter rates were 13.9 vs 53.8%, 11.0 vs 44.8%, and 2.9 vs 9.0%, respectively (p<0.0001). Weighted total goiter rate was 9.8% in 2001. Median (range) UIC in 2001 (no.=3329) was 165 (18-499) microg/l and in 1996 (no.=2917) was 205 (10-2300) microg/l (p<0.0001). In 2001 vs 1996, mean+/-SD for iodine salt content was 32.7+/-10.1 vs 33.0+/-10.2 ppm (p=0.68) in households and was 33.2+/-13.4 and 33.8+/-13.2 ppm (p=0.57) in factories, respectively. Among 7-10 yr old children in 2001 (no.=400) vs 1999 (no.=396), only 7-yr-old children in 2001 (the only group with probably no history of iodine deficiency) showed significant smaller thyroid volumes by ultrasonography compared to those in 1999., Conclusions: After 7 yr of optimized iodized-salt supplementation in Iran, adequate UIC values and marked reduction in goiter rate have been achieved.

Objective: To assess transient congenital hypothyroidism (TCH) etiologies in two Iranian cities., Materials and Methods: Cord dried blood spot samples were collected from neonates in Tehran and Damavand. Serum TSH and T4 were measured in those with cord TSH > or =20 mIU/l. Normal serum values at 2-3 weeks of age confirmed transient hyperthyrotropinemia (THT), while persistently abnormal levels revealed congenital hypothyroidism (CH). Normal serum TSH and T4 4-6 weeks after levothyroxine replacement therapy discontinuation at 2-3 yr of age differentiated TCH from persistent CH., Results: Among 50,409 screened newborns, 9 (1:5601 births) were diagnosed as TCH and compared to 88 full-term neonates (>/=37 weeks' gestation) with THT and 45 normal (cord TSH<20 mIU/l) neonates. At a median age of 11 days, median (range) serum TSH values in TCH, THT, and normal neonates were 36.8 (13-130), 3.6 (0.1-13.3), and 2.9 (0.7-8.0) mIU/l (p<0.0001) and serum T4 values were 97 (36-168), 142 (74-232), and 160 (79-228 nmol/l), respectively (p=0.002). Urinary iodine concentration (UIC) >220 microg/l was observed in 5 (55.6%) of TCH neonates. The occurrence of TCH was not associated with gender, parental consanguinity, mode of delivery, pre- or post-natal consumption of goitrogens and/or thyroid affecting medications, TSH receptor autoantibodies, or neonatal UIC., Conclusions: Elevated UIC was the most frequent finding in newborns with TCH but the distribution of excessive UIC was not significantly different among TCH, THT, and normal neonates. Since no other etiologies were found in TCH neonates without elevated UIC values, evaluation of other environmental and/or genetic factors is warranted.

Goiter rate, serum TSH, antithyroperoxidase (TPOAb), antithyroglobulin (TgAb) antibodies, and urinary iodine concentration (UIC) were evaluated 10-11 yr prior (1983-1984) and 5-6 yr after (1999-2000) national salt iodization in Iran. Pre- and post-iodization groups consisted of 465 and 1426 adults aged > or =20 yr, respectively, selected by random cluster sampling in Tehran province. Total, grade 1 and grade 2 goiter rates were 65.2, 53.1, and 12.1% in 1983-1984 vs 25.2, 15.5, and 9.7% in 1999-2000 (p<0.0001). Median serum TSH was 1.5 mIU/l in 1983-1984 vs 0.8 mIU/l in 1999-2000 (p<0.0001). Median TSH also decreased in 20-29, 30-39, 40-49, 50-59, and > or =60- yr-adults in 1983-1984 vs 1999-2000 (p<0.0001). In 1983-1984, positive TPOAb and positive TgAb were detected in 3.2 and 4%, respectively, using agglutination test. Corresponding values were 12.5 and 16.8% using immunoenzymometric assay in 1999-2000. Overt and subclinical hypothyroidism was present in 0 and 32.8/1000 in 1983-1984 vs 3.5 and 21.7/1000 in 1999-2000, respectively. Overt and subclinical hyperthyroidism was detected in 4.4 and 4.4/1000 in 1983-1984 vs 0.7 and 5.6/1000 in 1999-2000, respectively. Subclinical hypothyroidism in males was significantly more frequent in 1983-1984 vs 1999-2000 (odds ratio 5.02, 95% confidence interval 1.72-14.68; p=0.004). Salt iodization resulted in adequate UIC, decrease in serum TSH and subclinical hypothyroidism in males, and an increase in thyroid autoantibodies without significant change in thyroid abnormalities. Benefits of iodine supplementation far outweigh its hazards in Tehranian adults.

Introduction and Aims: Calcium and vitamin D play major roles in calcium homeostasis and skeletal development, especially during pregnancy. This study was conducted to determine changes in calcium, 25 hydroxy [25(OH)] vitamin D3 and other biochemical factors (PTH, osteocalcin, alkaline phosphatase, magnesium, phosphorus) related to calcium homeostasis and bone turnover during pregnancy and compare the values to those of non-pregnant women., Materials and Methods: In a cohort study, 48 pregnant women, in their first trimester of pregnancy (12+/-2.7 weeks), from 5 prenatal care centers, and 47 non-pregnant women randomly selected from the Tehran Lipid and Glucose Study (TLGS) population were enrolled. These pregnant women were followed in their second (26+/-1.9 weeks) and third trimesters (37+/-3.2 weeks) of pregnancy. Samples were drawn from June 2002 to March 2003. Including criteria were healthy women with no background of disease. Women using photo protection and calcium and vitamin D supplementation were excluded. A questionnaire was used to obtain demographic information for both groups. Venous blood samples were taken after 12-14 h of overnight fasting to measure serum calcium, phosphorus, magnesium, alkaline phosphatase, PTH, 25 (OH) vitamin D3 and serum osteocalcin levels. The repeated measures analysis of variance and t-test were used for statistical analysis. Data were matched for age and weight in both the case (in the first trimester) and control groups., Results: Significant differences were found in the mean serum levels of osteocalcin and alkaline phosphatase between the three trimesters of pregnancy (p< 0.001). Osteocalcin was significantly higher in the first trimester as compared to second and third trimesters of pregnancy. Alkaline phosphatase was significantly lower in the first trimester as compared to the second and third trimesters of pregnancy and their controls. There was also a significant difference in osteocalcin in the second and third trimesters and alkaline phosphatase in the first and third trimesters of pregnancy in comparison to the control group. The mean values of osteocalcin were 12.7+/-8.5, 8.1+/-6.9, 5.6+/-5.0 and 13.9+/-7.9 ng/ml, respectively, and mean values for alkaline phosphatase were 115+/-38, 125+/-37, 174+/-61 and 134+/-35.0 Iu/l, respectively. In the first trimester, alkaline phosphatase was lower and osteocalcin was higher than in the second and third trimesters. In the first trimester of pregnancy, 20 and 40% of women had 25(OH) vitamin D3 < 10 and < 20 ng/ml, respectively, and 19% of women had serum calcium levels < 8.6 mg/dl., Conclusion: 60% of women in the first trimester, 48% in the second and 47% in the third trimester had either severe or moderate vitamin D deficiency. It is recommended that the importance of calcium supplements with vitamin D in pregnant women be stressed for these individuals.

Thyrotoxicosis occurs more frequently during the post-partum period than at other times in women of childbearing age. Graves' disease and post-partum thyroiditis are two major causes of thyrotoxicosis in this period. The major task lies in differentiation of these two diseases in the post-partum period; since throtoxicosis caused by post-partum thyroiditis usually does not require treatment. The radioiodine uptake is elevated or normal in Graves' disease and low in post-partum thyroiditis, and TSH-receptor antibodies are positive in Graves' and negative in post-partum thyroiditis. Post-partum thyrotoxicosis due to Graves' disease may be treated with radioiodine but it requires radiation safety measurements for infant and is contraindicated if the mother is breast-feeding. Antithyroid drugs are the mainstay of the treatment of post-partum thyrotoxicosis. Recent investigations conclude that neither propylthiouracil nor methimazole cause any alterations in thyroid function and physical and mental development of infants breast-fed by lactating thyrotoxic mothers, and both can be safely administered in moderately high doses during lactation.

Background: One decade after universal salt iodization in Iran, goiter prevalence, urinary iodine concentration (UIC) and thyroperoxidase antibody (TPOAb) values were assessed among schoolchildren in Gorgan, Iran., Methods: From 2003-2004, 500 girls and 900 boys aged 7-11 yr were evaluated for goiter by palpation. UIC was measured in 183 randomly-selected goitrous children. Serum TSH, T4, and TPOAb were measured in 53 goitrous and 30 non-goitrous children with adequate UIC., Results: Goiter was detected in 370 (26.4%) children. Goiter was present in 31% of girls and 17% of boys age 9 (p<0.012); 37% of girls and 20% of boys age 10 (p<0.003); and 52% of girls and 19% of boys age 11 (p<0.0001). Median (range) UIC for all goitrous children sampled was 190 (20-600) microg/l; 220 (30590) in boys and 170 (20-600) in girls (p=0.001). Eight point seven percent of goitrous children and 22% of goitrous girls aged 10-11 had UIC<100 microg/l, while 47% of the goitrous children had UIC> or =200 microg/ l. TPOAb was present in 52.8% of goitrous children and 10% of non-goitrous children (p=0.0001). TPOAb was present in 53.9% of 10-11 and 22.7% of 7-9 yr old goitrous and non-goitrous children (p=0.003) with adequate UIC. Median (range) TSH was 2.9 (0.3-10.9) mlU/I in TPO-positive and 1.8 (0.5-4.1) in TPO-negative children (p=0.001)., Conclusions: Gorgan, Iran, is an iodine-sufficient area and almost half of schoolchildren have more than adequate UIC. TPOAb is associated with endemic goiter. Despite sufficient UIC overall, some school-aged girls remain at risk of iodine deficiency.

Objective: Auditory disturbances may be present in iodine deficient children. The aim of this study was to determine the effect of long-term iodine supplementation on auditory thresholds in iodine deficient children., Design and Methods: 70, 70 and 72 schoolchildren of an area of severe iodine deficiency were studied before intervention (1989), 3 yr after injection of 480 mg iodized oil (1992) and 7 yr after consumption of iodized salt (1999), respectively. Goiter was graded and serum T4, T3, TSH and thyroglobulin concentrations and urinary iodine levels were measured. Audiometry was performed with a pure tone audiometer., Results: There was significant decrease in the prevalence and severity of goiter and serum TSH and thyroglobulin concentrations, and significant rise in serum T4 in 1992 and 1999, as compared to 1989. Before iodine supplementation, hearing was abnormal in 44% of schoolchildren, mean hearing threshold was 15.8 +/- 5.9 and in all children was >10 dB. Mean hearing threshold decreased to 10.2 +/- 4.6 and 10.0 +/- 5.9, 3 and 10 yr after intervention (p < 0.001). Forty seven and 62% of children had thresholds < 10 dB in 1992 and 1999, respectively. Hearing thresholds > 15 dB were detected in 46, 11 and 10% of schoolchildren in 1989, 1992 and 1999, respectively (p < 0.001)., Conclusion: Continuous iodine supplementation permanantly improves the auditory thresholds of iodine deficient children.