Novel anthropometric indices for predicting type 2 diabetes mellitus.

BACKGROUND: This study aimed to compare anthropometric indices to predict type 2 diabetes mellitus (T2DM) among first-degree relatives of diabetic patients in the Iranian community. METHODS: In this study, information on 3483 first-degree relatives (FDRs) of diabetic patients was extracted from the database of the Endocrinology and Metabolism Research Center of Isfahan University of Medical Sciences. Overall, 2082 FDRs were included in the analyses. A logistic regression model was used to evaluate the association between anthropometric indices and the odds of having diabetes. Furthermore, a receiver operating characteristic (ROC) curve was applied to estimate the optimal cutoff point based on the sensitivity and specificity of each index. In addition, the indices were compared based on the area under the curve (AUC). RESULTS: The overall prevalence of diabetes was 15.3%. The optimal cutoff points for anthropometric measures among men were 25.09 for body mass index (BMI) (AUC = 0.573), 0.52 for waist-to-height ratio (WHtR) (AUC = 0.648), 0.91 for waist-to-hip ratio (WHR) (AUC = 0.654), 0.08 for a body shape index (ABSI) (AUC = 0.599), 3.92 for body roundness index (BRI) (AUC = 0.648), 27.27 for body adiposity index (BAI) (AUC = 0.590), and 8 for visceral adiposity index (VAI) (AUC = 0.596). The optimal cutoff points for anthropometric indices were 28.75 for BMI (AUC = 0.610), 0.55 for the WHtR (AUC = 0.685), 0.80 for the WHR (AUC = 0.687), 0.07 for the ABSI (AUC = 0.669), 4.34 for the BRI (AUC = 0.685), 39.95 for the BAI (AUC = 0.583), and 6.15 for the VAI (AUC = 0.658). The WHR, WHTR, and BRI were revealed to have fair AUC values and were relatively greater than the other indices for both men and women. Furthermore, in women, the ABSI and VAI also had fair AUCs. However, BMI and the BAI had the lowest AUC values among the indices in both sexes. CONCLUSION: The WHtR, BRI, VAI, and WHR outperformed other anthropometric indices in predicting T2DM in first-degree relatives (FDRs) of diabetic patients. However, further investigations in different populations may need to be implemented to justify their widespread adoption in clinical practice.

Reference range of testosterone and dehydroepiandrosterone sulfate levels in women during reproductive age in the Iranian population.

Backgrounds: To determine the average cutoff values of serum-free and total testosterone (FT, TT) and dehydroepiandrosterone sulfate (DHEAS) among healthy premenopausal women. Materials and Methods: Participants were women aged 18-55 years without signs and symptoms of hyperandrogenism (n = 489). Participants if Ferriman-Gallwey (FG) scores between 6 and 8 were considered a group located in the upper spectrum related to the normal hirsutism score (n = 30). DHEAS, TT, and FT levels were compared between different populations. Upper limits of 97.5 and 95 and lower limits of 5 and 2.5 percentiles were calculated to provide the reference intervals for DHEA, TT, and FT in the total sample and in the population with FG 6-8. Results: In the total population, the mean ± standard deviation (SD) serum FT, TT, and DHEAS levels were 1.40 ± 0.63 pg/mL, 0.42 ± 0.17 ng/mL, and 1.5 ± 0.97 µg/ml, respectively. The cutoff values of FT at 1.35 and TT at 0.49 were obtained for differentiating the patients with FG 6-8 scores from the normal population, with the corresponding specificity of 0.60, the sensitivity of 0.67, and area under the ROC curve (AUC) (confidence interval 95%) of 0.63 (0.52-0.73), P = 0.01 and 0.68 (0.58-0.78) P = 0.001, respectively. Conclusions: In our study, the mean ± SD serum FT level was 1.40 ± 0.63 pg/mL, the TT level was 0.42 ± 0.17 ng/mL, and the DHEAS level was 1.5 ± 0.97 µg/ml, in premenopausal women between 18 and 49 years of age. Furthermore, in a population with FG 6-8 score, a cutoff value of FT at 1.35 and TT at 0.49 was obtained. Although the irregular menstrual cycle did not change the reference range when compared with the normal group.

The association of exposure to air pollution with changes in plasma glucose indices, and incidence of diabetes and prediabetes: A prospective cohort of first-degree relatives of patients with type 2 diabetes.

Background: Increasing incidence rates of diabetes related to air pollution have been reported in high-income countries. However, few studies evaluated air pollution effect on plasma glucose indices, in addition to diabetes and prediabetes incidence in developing countries. This study investigated the association between exposure to common air pollutants and the changes plasma glucose indices over time. The incidence of type 2 diabetes (T2D) and prediabetes in future were also examined in association with exposure to air pollution. Materials and Methods: A total of 3828 first-degree relatives of patients with T2D who were prediabetes or had normal glucose tolerance (NGT) were enrolled in this study. Cox regression was used to assess the relationships between particulate matter (PM2.5 and PM10), nitrogen monoxide (NO), nitrogen dioxide, nitric oxides, sulfur dioxide (SO2), and ozone exposure and the incidence of T2D and prediabetes. We also applied a linear mixed model to assess the association between exposure to these air pollutants and changes in plasma glucose indices over time. Results: Air pollutants showed a significant positive association with changes in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and 2 h oral glucose tolerance (OGTT) in participants with NGT and prediabetes. The maximum increase in plasma glucose indices was associated with NO concentration. Our study also showed exposure to all air pollutants except SO2 was significantly associated with an increased risk of developing T2D and prediabetes (Hazard ratio > 1, P < 0.001). Conclusion: According to our results, exposure to air pollution increases the risk of T2D and prediabetes incidence in our population. The exposure to air pollutants was also associated with increasing trend in FPG, HbA1c, and OGTT levels in both groups of NGT and prediabetic participants.

Reference Intervals for Thyroid Hormones During the First Trimester of Gestation: A Report from an Area with a Sufficient Iodine Level.

A concern was raised 1 regarding the number of pregnant women in the analysis of reference range for the thyroid hormones in pregnancy 2, where we reported 185 cases and it was believed to be 145 cases.

The effect of alendronate on lipid profile of postmenopausal women with osteopenia and prediabetes: A randomized triple-blind clinical trial.

BACKGROUND: Prediabetes is a high-risk state for developing diabetes at an annual rate of 5%-10%. Early intervention can prevent further complications, including metabolic syndrome. Bisphosphonates are commonly used for osteoporotic postmenopausal women. The purpose of this study was to assess the effects of bisphosphonates on lipid profile including triglyceride (TG), total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) of prediabetic postmenopausal women with osteopenia. MATERIALS AND METHODS: In this triple-blind randomized controlled trial, sixty prediabetic, postmenopausal women with sufficient Vitamin D and osteopenia, aged 45-60 years, were randomly enrolled in two groups of intervention (receiving 70-mg alendronate for 12 weeks [duration for maximum metabolic effect of bisphosphonates], n = 30) and control (receiving placebo, n = 30) according to a randomized block procedure of size 2 and 1:1 allocation ratio. The primary outcome of the study, the lipid profile, was evaluated before and after the interventions. The effect of the intervention was assessed using analysis of covariance. RESULTS: The lipid profiles showed no significant differences to the mean values at the baseline in both the groups (all P > 0.05). At the end of the study, the differences between the groups were not significant for 25(OH) D3 (mean difference: -11.09, 95% confidence interval: -32.43-10.25), T (4.19, -30.58-38.97), cholesterol (8.13, -13.07-29.33), LDL-cholesterol (5.07, -10.18-20.31), and HDL-cholesterol (-0.86, -6.04-4.31) when the baseline values and confounders were adjusted (all P > 0.05). CONCLUSION: No statistically significant difference was detected in the serum lipid profile of prediabetic postmenopausal women with osteopenia as a result of alendronate intervention. More studies with larger sample sizes and longer intervention periods are recommended.

Patterns of changes in serum lipid profiles in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients.

BACKGROUND: Lipid abnormality pervasively is associated with the risk of type 2 diabetes mellitus. To the best of our knowledge, there is no study that has examined the longitudinal changes in a wide range of serum lipid profiles in prediabetic subjects in association with the risk of developing type 2 diabetes mellitus in the future. This study aimed to identify the patterns of changes in lipid profiles over time in prediabetic patients and to classify these subjects in order to highlight which patients are at high risk for future diabetes. METHODS: This prospective 16-year (2003-2019) cohort study was conducted among 1228 prediabetic subjects. The study subjects were followed, and the changes in their lipid profiles, including triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, were evaluated. The latent Markov model was used for data analysis. RESULTS: The mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The latent Markov model identified two latent states of subjects in terms of changes in lipid profiles: a low tendency to progress diabetes / high tendency to progress diabetes (74, 26%). The latent Markov model showed that the transition probability from a "low tendency to progress diabetic" state to a "high tendency to progress diabetic" state was lower than the transition probability from "high tendency to progress diabetic" state to "low tendency to progress diabetic" state. CONCLUSIONS: The present study showed that more than half of the first-degree relatives of T2DM had approximately normal lipid profiles and that these patients are more inclined to transition from a higher- to a lower-tendency diabetic state. These findings confirm the value of regular screening of first-degree relatives of T2DM. Moreover, preventive intervention strategies are recommended to reduce their risk of developing T2DM.

Prevalence and predictors of prediabetes and its coexistence with high blood pressure in first-degree relatives of patients with type 2 diabetes: A 9-year cohort study.

BACKGROUND: Prediabetes is strongly associated with high blood pressure; however, a little is known about prediabetes and high blood pressure comorbidity in the high-risk individuals. This is the first study in the world to assess the long-term effects of risk factors associated with high blood pressure and prediabetes comorbidity in the first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) patients. MATERIALS AND METHODS: The longitudinal data obtained from 1388 nondiabetic FDRs of T2DM patients with at least two visits between 2003 and 2011. We used univariate and bivariate mixed-effects logistic regressions with a Bayesian approach to identify longitudinal predictors of high blood pressure and prediabetes separately and simultaneously. RESULTS: The baseline prevalence of high blood pressure, prediabetes, and the coexistence of both was 27.4%, 19.1%, and 29.8%, respectively. The risks of high blood pressure and prediabetes were increased by one-unit raise in the age (odds ratio [OR] of high blood pressure: 1.419 (95% credible intervals [CI], 1.077-1.877), prediabetes: 1.055 (95% CI: 1.040-1.068)) and one-unit raise in remnant-cholesterol (OR of high blood pressure: 1.093 (95%CI, 1.067-1.121), and prediabetes: 1.086 (95% CI, 1.043-1.119)). Obese participants were more likely to have high blood pressure (OR: 2.443 [95% CI, 1.978-3.031]) and prediabetes (OR: 1.399 [95% CI, 1.129-1.730]) than other participants. CONCLUSION: We have introduced remnant-cholesterol, along with obesity and age, as a significant predictor of prediabetes, high blood pressure, and the coexistence of both in the FDRs of diabetic patients. Obesity index and remnant-cholesterol showed the stronger effects on high blood pressure and prediabetes comorbidity than on each condition separately.

Thyroid volume and nodular and diffuse thyroid diseases by ultrasonography in pregnant women: A case-control study.

BACKGROUND: Currently, it is shown that pregnancy may have an impact on the thyroid that can be leading to pregnancy complications such as abortion, preeclampsia, and preterm delivery. The objective was to compare the thyroid volume, number and characteristics of thyroid nodules, and prevalence of diffuse thyroid diseases in a sample of Iranian pregnant women in the first trimester to nonpregnant women. MATERIALS AND METHODS: This case-control study was conducted on 298 pregnant and 290 nonpregnant women. Thyroid volume, maximum diameter of thyroid nodules and prevalence of moderate to highly suspicious thyroid nodules, Hashimoto's appearance and goiter were assessed using thyroid ultrasonography. Antithyroperoxidase (TPO) antibodies were measured if the sonographic features were highly suggested for Hashimoto's thyroiditis. RESULTS: The mean of total thyroid volume in pregnant and nonpregnant women was 6 and 6.5 ml, respectively (P = 0.053), and the median (interquartile range) was 6.2 and 5.5, respectively. Nodules were observed in 16.4% of pregnant and 16.6% of nonpregnant women (P = 0.845). Hashimoto's thyroiditis was detected in 6.7% of pregnant and 12.4% of nonpregnant women (P = 0.013). Anti-TPO antibodies were detected in 5% of pregnant and 9.3% of nonpregnant women (P = 0.034). CONCLUSION: The thyroid volume and nodule characteristics in the first trimester of pregnancy were similar to nonpregnant women. Hashimoto's thyroiditis and anti-TPO antibodies in pregnant women were significantly lower than in nonpregnant women.

Thyroid-stimulating hormone (TSH) serum levels and risk of spontaneous abortion: A prospective population-based cohort study.

OBJECTIVE: Thyroid dysfunction, a common complication of pregnancy, is associated with adverse obstetric and neonatal consequences. This study aimed to determine the effect of TSH levels on early pregnancy outcome in a prospective population-based cohort study. DESIGN AND METHODS: The serum TSH, free thyroxine, free triiodothyronine, thyroid peroxidase antibody levels and urinary iodine concentration of 418 pregnant women in their first trimester of pregnancy were measured. According to the American Thyroid Association (ATA) and the local reference ranges for TSH, women were divided into two groups of 0.1-2.5, >2.5 mIU/L and 0.2-4.6, >4.6 mIU/L. The risk of spontaneous abortion (SA) was calculated for each group. RESULTS: Spontaneous abortion was detected in 7.2% (n = 30) of total 418 pregnancies. Women with TSH levels > 2.5 mIU/L had an increased risk of SA, compared to women with TSH levels of 0.1-2.5 mIU/L (relative risk [RR] 3.719, 95% confidence interval [CI]:1.713-8.074). The risk of SA was increased in women with TSH levels > 4.6 mIU/L (RR 5.939, 95% CI: 1.711-20.620). The rate of SA was increased by 78% for every unit increase in standard deviation of TSH concentration (RR 1.35, 95% CI: 1.09-1.70). The rate of miscarriages in the treated group by levothyroxine was 9.8% (n = 6) compared to 28.6% (n = 8) in the untreated group (P = 0.024). CONCLUSIONS: Our finding suggests that the upper limit for the TSH normal range should be redefined to <2.5 mIU/L during the first trimester of gestation. The local upper limit was 4.6 mIU/L, consistent with 4.0 mIU/L cut-off value recommended by the ATA.

Reference Intervals for Thyroid Hormones During the First Trimester of Gestation: A Report from an Area with a Sufficient Iodine Level.

The physiological changes during pregnancy modulate the endocrine system. Therefore, both the American and the European thyroid associations recommend the use of local trimester-specific reference intervals. The purpose of this study was to establish the first trimester reference intervals for thyroid function tests in the central area of Iran. We examined 436 pregnant women in their first trimester of pregnancy, and 444 non-pregnant women in a cross sectional study. Serum levels of thyroid stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, urinary iodine concentration (UIC), and thyroid volume were measured for all subjects. The first trimester-specific reference intervals (2.5th-97.5th percentile) were determined for 185 pregnant women and 256 non-pregnant women with negative TPOAb, adequate iodine level (UIC≥150 µg/l in pregnant and UIC≥100 µg/l in non-pregnant women), and normal thyroid examination. We calculated multiples of the median (MoM) for TFTs to normalize the obtained data. The first trimester-specific reference intervals of serum TSH, FT4, and FT3 for pregnant women were 0.20-4.60 mIU/l, 9.0-18.02 pmol/l, and 3.40-5.64 pmol/l, respectively, while the corresponding figures for non-pregnant women were 0.59-5.60 mIU/l, 9.52-19.30 pmol/l, and 3.70-5.55 pmol/l, respectively. The first and 99th percentile MoM of TSH in pregnant women in their first-trimester was 0.06-4.62. The local normal reference ranges for the first trimester of pregnancy in central region of Iran were different from the ranges suggested by the ATA.

Effects of somatostatin analog treatment on cardiovascular parameters in patients with acromegaly: A systematic review.

BACKGROUND: There is a belief that in patients with acromegaly, first-generation somatostatin analogs (SSAs) might improve cardiovascular (CV) structure and function. However, most published clinical trials involved only a few patients and their results are rather variable. We aimed to conduct a systematic review on available studies on the impact of these drugs on CV parameters. MATERIALS AND METHODS: A literature search was conducted in MEDLINE (OVID), EMBase, Cochrane, and ISI Web of Science for citations published until April 30 2018 to identify studies on our objective that considered changes in CV parameters. For this search, we established a Boolean search strategy using keywords related to "acromegaly," "Somatostatin analog," and "cardiovascular diseases and parameters." All study types except for case reports or conference abstracts were included. Twenty-four studies (n = 558) fulfilled the inclusion criteria and were selected for final analysis. RESULTS: In 12 studies (n = 350), decrease in heart rate (HR) and in 4 studies (n = 128), decrease in blood pressure (BP) was significant. In 15 studies (n = 320), left ventricular mass index (LVMi) changes were significant. In 9 studies (n = 202), the early diastole to peak velocity flow in late diastole (E/A ratio) was evaluated, and in 5 of them (n = 141), the improvement was significant. Eighteen studies (n = 366) examined changes in left ventricular ejection fraction (LVEF), 5 of which (n = 171) reported that these changes were significant. Decrease of left ventricular end-diastolic diameter was reported in only 2 studies (n = 27). CONCLUSION: We found that first-generation SSAs have a beneficial effect on cardiac parameters such as HR and LVMi. For other parameters such as LVEF, BP, LV diameter, and E/A ratio, we were not able to draw a firm conclusion.

DEXAMETHASONE STRESS TEST: A PILOT CLINICAL STUDY FOR IDENTIFICATION OF INDIVIDUALS HIGHLY PRONE TO DEVELOP TYPE 2 DIABETES.

OBJECTIVE: We examined whether the "Dexamethasone Stress Test" exhibits the requisite high predictive ability to identify individuals highly prone to develop type 2 diabetes mellitus (T2DM). METHODS: Seven years ago, we administered an oral glucose tolerance test (OGTT) to 33 individuals without T2DM and repeated the OGTT 24 hours after a single oral dose of 8 mg dexamethasone (Dex); all participants had a first-degree relative with T2DM, and close to half had prediabetes. We calculated receiver operating characteristic (ROC) curves for all parameters derived from the OGTT before and after Dex in individuals who subsequently developed diabetes compared to individuals who did not. RESULTS: At 7 years of follow-up, 9 individuals had developed T2DM, while 24 remained without diabetes. None of the OGTT-derived parameters before administration of Dex had an area under the ROC curve of >0.8. However, 24 hours after Dex, three parameters, including fasting plasma insulin, homeostatic model assessment-insulin resistance, and 2-hour plasma glucose level, exhibited areas under the ROC curves of 0.84, 0.86, and 0.92, respectively. CONCLUSION: The Dexamethasone Stress Test appears to be a good to excellent test in identifying individuals highly prone to develop T2DM. ABBREVIATIONS: AUC = area under the curve; Dex = dexamethasone; HOMA-IR = homeostatic model assessment-insulin resistance; NGT = normal glucose tolerance; OGTT = oral glucose tolerance test; PreDiab = prediabetes; ROC = receiver operating characteristic; T2DM = type 2 diabetes mellitus.

Thyroid function test reference ranges in the first trimester of gestation and pregnancy outcomes: Protocol and preliminary results for cohort population-based study Isfahan, Iran.

BACKGROUND: This paper presents the protocol and primary findings of pregnancy cohort population-based study in Isfahan, Iran. MATERIALS AND METHODS: In this cohort, 418 pregnant and 438 nonpregnant women were enrolled. In the first phase, serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, and urinary iodine concentration (UIC) were measured. Furthermore, the thyroid ultrasound was also performed. According to the results of thyroid function tests in the first phase, local reference range for TSH, FT4, and FT3 in pregnant and nonpregnant women are determined. The 2.5th and 97.5th percentiles are determined as limits of the reference ranges. In the second phase, all pregnant women underwent prenatal care visits in each trimester and they followed for 7 days after delivery and the pregnancy outcomes data are reported. RESULTS: The mean ± standard deviation for TSH, FT4, FT3, and UIC in the first trimester of gestation was 1.84 ± 1.32 mIU/L, 1.01 ± 0.15 ng/dL, 4.50 ± 0.64 pmol/L, and 172.0 ± 90.29 µg/L, respectively. In nonpregnant women, these values for TSH, FT4, FT3, and UIC were 2.58 ± 1.77 mIU/L, 1.10 ± 0.21 ng/dL, 4.49 ± 0.57 pmol/L, and 190.0 ± 109.6 µg/L, respectively. CONCLUSION: The results of the present study could contribute to establish a local thyroid function tests reference ranges in the first trimester of pregnancy. It could possibly be effective on making a local reference value to prevent of thyroid disease misdiagnosis during pregnancy and adverse pregnancy outcomes.

Effects of Vitamin D deficiency treatment on metabolic markers in Hashimoto thyroiditis patients.

BACKGROUND: The aim of the current trial was to investigate the effect of Vitamin D treatment on metabolic markers in people with Vitamin D deficiency and thyroid autoimmunity. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled clinical trial, 65 Vitamin D deficient euthyroid or hypothyroid patients with positive TPO-Ab were enrolled. They randomly allocated into two groups to receive oral Vitamin D3 (50000 IU weekly) and placebo for 12 weeks. Serum concentration of calcium, phosphorus, albumin, C-reactive protein, blood urea nitrogen, creatinine, glycated hemoglobin (HbA1c), insulin, fasting plasma glucose (FPG), triglyceride (TG), total cholesterol, and high-density lipoprotein were measured in both groups before and after the trial. Homeostasis model assessment estimates of beta cell function (HOMA-B) and HOMA-insulin resistance (HOMA-IR) were calculated before and after trial in both groups. RESULTS: Thirty-three and thirty-two participants were allocated to Vitamin D-treated and placebo-treated groups, respectively. Mean (standard error) level of Vitamin D increased significantly in Vitamin D-treated group (45.53 [1.84] ng/mL vs. 12.76 [0.74] ng/mL, P = 0.001). The mean of HbA1c and insulin was increased significantly both in Vitamin D-treated and placebo-treated groups (P < 0.05). Other variables did not meet a significant change after trial (P = NS). In between-group comparison, there was not any significant difference between Vitamin D-treated and placebo-treated groups regarding measures of HOMA-B, HOMA-IR, FPG, HbA1c, and TG (P = NS). CONCLUSION: Our findings showed that weekly 50000 IU oral Vitamin D3 for 12 weeks did not improve metabolic markers, IR, or insulin secretion in Vitamin D deficient patients with Hashimoto thyroiditis.

Effect of Vitamin D deficiency treatment on thyroid function and autoimmunity markers in Hashimoto's thyroiditis: A double-blind randomized placebo-controlled clinical trial.

BACKGROUND: The link between autoimmune thyroid diseases and Vitamin D deficiency has been reported. However, there are controversies in this regard. We conducted a double-blind randomized placebo-controlled clinical trial to investigate the effect of Vitamin D deficiency treatment on thyroid function and autoimmunity marker (thyroid peroxidase antibody [TPO-Ab]) in patients with Hashimoto's thyroiditis. MATERIALS AND METHODS: Fifty-six patients with Hashimoto's thyroiditis and Vitamin D deficiency (25-hydroxyvitamin D level ≤20 ng/mL) were randomly allocated into two groups to receive Vitamin D (50000 IU/week, orally) or placebo for 12 weeks, as Vitamin D-treated (n = 30) and control (n = 26) groups, respectively. TPO-Ab, thyroid-stimulating hormone (TSH), parathormone, calcium, albumin, and creatinine concentrations were compared before and after trial between and within groups. The data were presented as mean (standard error [SE]) and analyzed by appropriate tests. RESULTS: Mean (SE) of Vitamin D was increased in Vitamin D-treated group (45.5 [1.8] ng/mL vs. 12.7 [0.7] ng/mL, P = 0.01). Mean (SE) of TPO-Ab did not significantly change in both groups (734 [102.93] IU/mL vs. 820.25 [98.92] IU/mL, P = 0.14 in Vitamin D-treated and 750.03 [108.7] [IU/mL] vs. 838.07 [99.4] [IU/mL] in placebo-treated group, P = 0.15). Mean (SE) of TSH was not changed in both groups after trial, P = 0.4 and P = 0.15 for Vitamin D-treated and control groups, respectively. No significant difference was observed between two study groups in none studied variables (P > 0.05). CONCLUSION: Vitamin D treatment in Vitamin D deficient patients with Hashimoto's thyroiditis could not have significant effect on thyroid function and autoimmunity.

Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial.

BACKGROUND: The people with prediabetes have insulin resistance (IR). IR may affect thyroid function, size and nodules. We investigated the effects of metformin on the thyroid gland in prediabetic people. MATERIALS AND METHODS: In a randomized, double-blind placebo-control clinical trial, 89 people with prediabetes, aged 18-65 years were studied for 3 months. They were divided into two, metformin (n = 43) and placebo (n = 46) treated groups. Serum thyroid stimulating hormone (TSH) was measured and thyroid nodules and volume was studied by ultrasonography. The data were compared between and within groups, before and after the study. RESULTS: Mean of the baseline characteristics in metformin and placebo-treated groups had no statistically significant difference. At the end of the study, serum TSH was not significantly different between the two groups. However, if the TSH range was divided into two low normal (0.3-2.5 µU/ml) and high-normal (2.6-5.5 µU/ml) ranges, significant decrease was observed in metformin-treated group with a high-normal basal serum TSH (P = 0.01). Thyroid volume did not change in metformin-treated group. However, in placebo-treated group, the thyroid was enlarged (P = 0.03). In 53.9% of participants, thyroid nodule was observed. There was just a decrease in the volume of small solid (not mixed) nodules from median of 0.07 ml to 0.04 ml in metformin-treated group (P = 0.01). CONCLUSION: In prediabetic people, metformin decreases serum TSH, only, in those people with TSH >2.5 µU/ml and reduces the size of small solid thyroid nodules. It also prevents an increase in the thyroid volume.

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

Defining gestational thyroid dysfunction through modified non-pregnancy reference intervals: an individual participant meta-analysis.

BACKGROUND: Establishing local trimester-specific reference intervals for gestational TSH and FT4 is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific non-pregnancy reference intervals as compared to trimester-specific reference intervals. METHODS: We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the non-pregnancy reference intervals included an absolute modification (per 0.1 mU/L TSH or 1 pmol/L FT4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 to 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity and positive predictive value (PPV) of aforementioned methodologies with population-based trimester-specific reference intervals. RESULTS: The final study population comprised 52,496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity 0.70, confidence interval [CI] 0.47-0.86; PPV 0.64, CI 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity 0.91, CI 0.67-0.98; PPV 0.71, CI 0.58-0.80). Absolute and fixed modifications yielded similar results. Confidence intervals were wide, limiting generalizability. CONCLUSION: We could not identify modifications of non-pregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned towards studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.