Publications by authors named "Maryam Tohidi"

118 Publications

National trends in cardiovascular health metrics among Iranian adults using results of three cross-sectional STEPwise approaches to surveillance surveys.

Sci Rep 2021 Jan 8;11(1):58. Epub 2021 Jan 8.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

To examine the trends of 7 cardiovascular health metrics (CVH metrics) incorporate of smoking, physical activity, diet, body mass index (BMI), fasting plasma glucose (FPG), total cholesterol (TC), and blood pressure (BP) level during three cross-sectional STEPwise approaches to surveillance (STEPS), 2007-2016, among Iranian adults. The study population consisted of 19,841 women and 17,243 men, aged 20-65 years. The CVH metrics were categorized as 'ideal', 'intermediate', and 'poor'. The sex-stratified weighted prevalence rate of each CVH metrics was reported. The conditional probability of each poor versus combined intermediate and ideal metric was analyzed using logistic regression. In 2016 compared to 2007, the prevalence of poor BP level (20.4% vs. 23.7%), smoking (13.7% vs. 23.8%), TC ≥ 240 mg/dl (2.4% vs. 11.2%) and FPG < 100 mg/dl (75.6% vs. 82.3%) declined, whereas poor physical activity level (49.7% vs. 30%), poor healthy diet score (38.1% vs. 4.1%), BMI levels ≥ 25 kg/m (62.8% vs. 57.8%) increased. Despite a high prevalence of obesity among women, it remained constant in women but showed an increasing trend in men; moreover, the trends of low physical activity and current smoking were better for women. Despite some improvement in CVH metrics, < 4% of Iranian adults meet ≥ 6 CVH metrics in 2016; this issue needs intervention at the public health level using a multi-component strategy.
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http://dx.doi.org/10.1038/s41598-020-79322-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794314PMC
January 2021

Recurrence of a neuroendocrine tumor of adrenal origin: a case report with more than a decade follow-up.

BMC Endocr Disord 2021 Jan 7;21(1). Epub 2021 Jan 7.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Yamen Street, Velenjak, Tehran, Iran.

Background: Neuroendocrine tumor (NET) with adrenocorticotropic hormone (ACTH) secretion are very rare. To our knowledge, no follow-up study is published for ACTH-secreting NET, regardless of the primary site, to show second occurrence of tumor after a long follow-up, following resection of primary tumor.

Case Presentation: Here, we describe a 49-year-old-man with cushingoid feature, drowsiness and quadriparesis came to emergency department at December 2005. Laboratory tests revealed hyperglycemia, metabolic alkalosis, severe hypokalemia, and chemical evidence of an ACTH-dependent hypercortisolism as morning serum cortisol of 57 μg /dL without suppression after 8 mg dexamethasone suppression test, serum ACTH level of 256 pg/mL, and urine free cortisol of > 1000 μg /24 h. Imaging showed only bilateral adrenal hyperplasia, without evidence of pituitary adenoma or ectopic ACTH producing tumors. Importantly, other diagnostic tests for differentiating Cushing disease (CD) from ectopic ACTH producing tumor, such as inferior petrosal sinus sampling (IPSS), corticotropin releasing hormone (CRH) stimulation test, octreotide scan or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan were not available in our country at that time. Therefore, bilateral adrenalectomy was performed that led to clinical and biochemical remission of hypercortisolism and decreased ACTH level to < 50 pg/mL, findings suggestive of a primary focus of NET in adrenal glands. After 11 years uncomplicated follow up, the ACTH level elevated up to 341 pg/mL and re-evaluation showed a 2 cm nodule in the middle lobe of the right lung. Surgical excision of the pulmonary nodule yielded a carcinoid tumor with positive immunostaining for ACTH; leading to decrease in serum ACTH level to 98 pg/mL. Subsequently after 7 months, serum ACHT levels rose again. More investigation showed multiple lung nodules with metastatic bone lesions accompanied by high serum chromogranin level (2062 ng/mL), and the patient managed as a metastatic NET, with bisphosphonate and somatostatin receptor analogues.

Conclusion: This case of surgically-treated NET showing a secondary focus of carcinoid tumor after one decade of disease-free follow-up emphasizes on the importance of long-term follow-up of ACTH-secreting adrenal NET.
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http://dx.doi.org/10.1186/s12902-020-00673-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791754PMC
January 2021

Urinary sodium-to-potassium ratio: a simple and useful indicator of diet quality in population-based studies.

Eur J Med Res 2021 Jan 6;26(1). Epub 2021 Jan 6.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Current evidence regarding the prognostic relevance of urinary sodium-to-potassium ratio (Na-to-K ratio), as an indicator of diet quality is limited. This study was conducted to investigate whether urinary Na-to-K ratio could be related to habitual dietary patterns, in a general population.

Methods: This study was conducted in the framework of the Tehran Lipid and Glucose Study (2014-2017) on 1864 adult men and women. Urinary Na and K concentrations were measured in the morning spot urine samples. Dietary intakes of the participants were assessed using a validated 147-item Food Frequency Questionnaire (FFQ) and major dietary patterns were obtained using principal component analysis. Mediterranean dietary pattern and Dietary Approaches to Stop Hypertension (DASH) score, were also calculated. Multivariable-adjusted linear regression was used to indicate association of dietary patterns and urinary Na-to-K ratio.

Results: Mean (± SD) age of participants was 43.7 ± 13.9 years and 47% were men. Mean (± SD) urinary Na, K and the ratio was 139 ± 41.0 and 57.9 ± 18.6 mmol/L, 2.40 ± 0.07, respectively. Higher urinary Na-to-K ratio (> 2.37 vs. < 1.49) was related to lower intakes of vegetables (282 vs. 321 g/day), low-fat dairy (228 vs. 260 g/day) and fruits (440 vs. 370 g/day). Western dietary pattern was related to higher urinary Na-to-K ratio (β = 0.06; 95% CI 0.01, 0.16). Traditional dietary pattern, Mediterranean and DASH diet scores were inversely associated with urinary Na-to-K ratio (β = - 0.14; 95% CI - 0.24, - 0.11, β = - 0.07; 95% CI - 0.09, - 0.01, β = - 0.12; 95% CI - 0.05, - 0.02, respectively).

Conclusions: Spot urinary Na-to-K ratio may be used as a simple and inexpensive method to monitor diet quality in population-based epidemiological studies.
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http://dx.doi.org/10.1186/s40001-020-00476-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788983PMC
January 2021

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

Endocr Res 2021 Feb 7;46(1):37-43. Epub 2020 Dec 7.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran, Iran.

: To determine age and sex-specific thyrotropin (TSH) and free thyroxine (FT4) reference ranges according to body mass index (BMI) categories. : With regards to the National Academy of Clinical Biochemistry (NACB) criteria, a total of 2818 individuals from the Tehran Thyroid Study population was selected and categorized in three BMI groups. : TSH levels did not differ significantly between BMI groups ( = .054). Females had statistically higher TSH levels than males in all BMI categories ( < .001). According to age-specific analyses, the youngest category (20-29 years) had the highest median values of serum TSH in all BMI groups. With increasing BMI, the 2.5 percentile of TSH remained approximately unchanged and the 97.5 percentile showed an increasing pattern. FT4 level was significantly higher in the normal weight group compared to obese individuals ( < .001); females had significantly lower FT4 levels than males in normal weight and obese groups ( < .001). According to age categories, the youngest group (20-29 years) had higher levels of FT4 than the elderly group in all BMI categories. A decreasing pattern in both 2.5 and 97.5 percentiles of FT4 was observed along with increasing BMI. : Compared to the normal weight population, obese individuals have slightly lower FT4 concentrations accompanied by similar TSH levels. With increasing BMI, upper limits of TSH and FT4 show increasing and decreasing patterns, respectively.
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http://dx.doi.org/10.1080/07435800.2020.1854778DOI Listing
February 2021

Nasopharyngeal B-cell lymphoma with pan-hypopituitarism and oculomotor nerve palsy: a case report and review of the literature.

BMC Endocr Disord 2020 Nov 3;20(1):163. Epub 2020 Nov 3.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Parvaneh Street, P.O. Box: 19395-4763, Tehran, Velenjak, Iran.

Background: Primary nasopharyngeal lymphoma (NPL) is a very rare tumor of Waldeyer ring (WR) lymphoid tissue. It is challenging to differentiate lymphoma infiltration of pituitary from a pituitary adenoma, meningioma infiltration, and other sellar lesions to plan a suitable treatment strategy. We presented for the first time a unique case of NPL with an unusual presentation of oculomotor nerve palsy associated with pan-pituitary involvement in a diabetic patient.

Case Presentation: A 64-year old diabetic woman with no previous history of malignancy presented with intermittent diplopia for about the last nine months. Severe headache, left eye ptosis and hypoglycemic episodes were added to her symptoms after a while. Further complaints include generalized weakness, loss of appetite, generalized musculoskeletal pain, and 6-7 kg weight loss within six months. Her family history was unremarkable. Physical examinations of eyes indicated left eye 3rd, 4th, and 6th nerve palsy. But, she was not anisocoric, and the pupillary reflexes were normal on both eyes. No lymphadenopathy, organomegaly and other abnormalities were found. Magnetic resonance imaging (MRI) showed a heterogeneous enhancement in the seller and suprasellar regions, enlargement of the stalk, parasellar dural enhancement and thickening of the sphenoid sinus without bone erosion. Also, both cavernous sinuses were infiltrated and both internal carotid arteries were encased by the neoplastic lesion. It suggested an infiltrative neoplastic lesion which compressed the cranial nerves. Pituitary hormone levels assessment indicated a pan-hypopituitarism. Following nasopharyngeal mucosal biopsy, the immunohistochemistry (IHC) findings revealed a low-grade non-Hodgkin's B-cell lymphoma. Systemic workup, including cerebrospinal fluid (CSF) studies, bone marrow aspiration, chest and abdominopelvic high-resolution computed tomography (HRCT) indicated no other involvement by the lymphoma. After chemotherapy courses, central adrenal insufficiency, partial central diabetes incipidious (CDI) and central hypothyroidism have been resolved. To our best knowledge, we found 17 cases of NPL with cranial nerve palsy, 1 case of NPL with pan-hypopituitarism and no NPL case with both cranial nerve palsy and pituitary dysfunction.

Conclusions: The incidence of cranial neuropathy in patients with diabetes should not merely be attributed to diabetic neuropathy without further evaluation.
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http://dx.doi.org/10.1186/s12902-020-00644-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607655PMC
November 2020

Assessment of the simultaneous effect of hypothyroidism and thyroid autoimmunity with gestational diabetes on the incidence of type 2 diabetes.

BMC Endocr Disord 2020 Oct 1;20(1):150. Epub 2020 Oct 1.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, Tehran, Iran.

Introduction: Despite the evidence available on the adverse impact of gestational diabetes (GDM) and thyroid disorders on developing type 2 diabetes (T2DM), the concurrent influence of these disorders on the incidence of T2DM has not been reported yet.

Methods: In this prospective study, 1894 non-diabetic women aged 20 to 60 years, with a history of at least one term delivery, without diagnosed hyperthyroidism were selected at the initiation of the Tehran Thyroid Study (TTS). Pooled logistic regression analyses were used to investigate the association of GDM, thyroid disorders i.e., hypothyroidism and/or thyroid peroxidase antibody (TPOAb) positivity and interaction between GDM and thyroid disorders with the risk of incident T2DM.

Results: Of the 1894 participants of the present study, 346 (18.3%) had a history of GDM, and 832 (43.9%) had thyroid disorders. The total cumulative incidence rate of T2DM at the median follow-up time of ~ 12 years was overall 12/1000 person-years (95% confidence interval (CI): 10/1000-13/1000), with an incidence rate of 16/1000 (95%CI: 13/1000-20/1000) in women with GDM; and 11/100,000 (95%CI: 9/100,000-12/1000) among those without GDM. After adjustment for age, the risk of incident T2DM increased among individuals with the previous GDM compared to women without a history of GDM (odds ratio (OR): 1.54, 95%CI: 1.06, 2.25). No significant associations were found between either thyroid disorders or the interaction between GDM and thyroid disorders with the development of T2DM; (OR: 1.14, 95%CI: 0.82, 1.58) and (OR: 1.27, 95%CI: 0.66, 2.43), respectively.

Conclusion: GDM and thyroid disorders have no concurrent impacts on the incidence of T2DM.
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http://dx.doi.org/10.1186/s12902-020-00627-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528385PMC
October 2020

The impact of triglyceride-glucose index on incident cardiovascular events during 16 years of follow-up: Tehran Lipid and Glucose Study.

Cardiovasc Diabetol 2020 09 29;19(1):155. Epub 2020 Sep 29.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24 Aarabi St. Velenjak, P.O. Box: 19395-4763, Tehran, Iran.

Background: To investigate whether the Triglyceride-Glucose index (TyG-index) is associated with increased risk of cardiovascular diseases (CVD)/coronary heart disease (CHD).

Methods: A total of 7521 Iranians aged ≥ 30 years (male = 3367) were included in the study. Multivariate Cox regression analyses (adjusted for age, gender, waist circumference, body mass index, educational level, smoking status, physical activity, family history of CVD, type 2 diabetes, hypertension, low and high density lipoprotein cholesterol, and lipid lowering drugs) were used to assess the risk of incident CVD/CHD across quintiles and for 1-standard deviation (SD) increase in the TyG-index. The cut off point for TyG-index was assessed by the minimum value of [Formula: see text]. We also examined the added value of the TyG-index in addition to the Framingham risk score when predicting CVD.

Results: During follow-up, 1084 cases of CVD (male = 634) were recorded. We found a significant trend of TyG-index for incident CVD/CHD in multivariate analysis (both Ps for tend ≤ 0.002). Moreover, a 1-SD increase in TyG-index was associated with significant risk of CVD/CHD in multivariate analysis [1.16 (1.07-1.25) and 1.19 (1.10-1.29), respectively]. The cut-off value of TyG-index for incident CVD was 9.03 (59.2% sensitivity and 63.2% specificity); the corresponding value of TyG-index for incident CHD was 9.03 (60.0% sensitivity and 62.8% specificity), respectively. Although no interaction was found between gender and TyG-index for CVD/CHD in multivariate analysis (both Ps for interaction > 0.085), the significant trend of TyG-index was observed only among females for incident CVD (P = 0.035). A significant interaction was found between age groups (i.e. ≥ 60 vs < 60 years) and TyG-index for CVD outcomes in the multivariate model (P-value for interaction = 0.046). Accordingly, a significant association between the TyG-index and outcomes was found only among the younger age group. Among the population aged < 60 the addition of TyG-index to the Framingham risk score (FRS) did not show improvement in the predictive ability of the FRS, using integrated discrimination improvement.

Conclusion: The TyG-index is significantly associated with increased risk of CVD/CHD incidence; this issue was more prominent among the younger population. However, adding TyG-index to FRS does not provide better risk prediction for CVD.
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http://dx.doi.org/10.1186/s12933-020-01121-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526412PMC
September 2020

Effects of oral contraceptives on the quality of life of women with polycystic ovary syndrome: a crossover randomized controlled trial.

Health Qual Life Outcomes 2020 Aug 31;18(1):293. Epub 2020 Aug 31.

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran.

Background And Objective: A limited number of studies have evaluated the effects of oral contraceptives (OCs) on the quality of life (QOL) of polycystic ovary syndrome (PCOS) patients. This study aimed to compare the effects of using OCs containing levonorgestrel (LNG) and those containing desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP) for 6 months on the QOL with PCOS.

Methods: In this crossover randomized controlled 6-arm trial, 200 eligible patients with PCOS scheduled for OC therapy were randomly assigned to one of the 6 study arms. All 6 arms include two 6-month treatment periods, one period with OCs containing LNG, and the other with each of the 3 OCs containing DSG, CPA, or DRSP. Outcomes of interest were the total score of QOL and its domains, which were assessed using a specific and valid health-related quality of life questionnaire for PCOS, which is consisted of six domains, including psychosocial-emotional, self-image, fertility, sexual function, hirsutism, and obesity- menstrual disorders.

Results: Finally, a total of 88 patients were analyzed for this study. The results showed that use of OCs containing DSG, CPA, and DRSP for 3 months was not associated with significant differences in the total scores of QOL compared to those OCs containing LNG, whereas, after 6 months of treatment, patients treated with OCs containing CPA had more improvements in their total scores of QOL, in comparison to OCs containing LNG (P < 0.042). We found no significant differences in QoL domains, including psychosocial-emotional, self-image, fertility, sexual function, hirsutism, and obesity-menstrual disorders after 3-6 months of treatment with DSG, CPA, or DRSP, compared to LNG. The sequence and period effects were not significant in any of the analyses at 3 and 6 months of treatment. The carry-over effect was not significant for most outcomes assessed.

Conclusions: This crossover study demonstrated non-inferiority of OCs with newer generation progestins on different domains of QOL, in comparison with older compounds, although usage of products containing CPA was significantly associated with more improvement in total QOL of PCOS patients, compared to those containing LNG after 6-month of treatment.

Trial Registration: IRCT201702071281N2 .
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http://dx.doi.org/10.1186/s12955-020-01544-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460764PMC
August 2020

Effect of Bedtime Melatonin Administration in Patients with Type 2 Diabetes: A Triple-Blind, Placebo-Controlled, Randomized Trial.

Iran J Pharm Res 2019 ;18(Suppl1):258-268

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran .

Melatonin is widely available as over the counter product. Despite promising effects of melatonin supplementation on glycemic control, there is a significant heterogeneity between studies. The current study aimed at determining the effect of melatonin on fasting blood glucose (FBG), insulin resistance/sensitivity indices, glycosylated hemoglobin A1c (HbA1c), and high sensitivity C-reactive protein (hs-CRP) among type 2 diabetes mellitus (T2D) population during 8 weeks in a randomized, triple-blind, placebo-controlled trial. Thirty four subjects with the mean age ± standard deviation of 57.74 ± 8.57 years and 36 subjects with the mean age of 57.61 ± 9.11 years were allocated to 6 mg nightly melatonin and placebo groups, respectively. Melatonin and placebo groups were matched by age, gender, body mass index, and duration of diabetes. Also, there was no significant difference in laboratory findings except for HbA1c, which was lower in the placebo group (7.00 ± 0.89% vs 7.60 ± 1.47%, =0.042). After trial completion, the increase of serum levels of melatonin was greater in the intervention than the placebo group (3.38 ± 1.33 vs 0.94 ± 1.28 ng/L, =0.192). Moreover, compared to placebo group, among melatonin users, homeostasis model assessment of insulin resistance (HOMA1-IR) tended to be unfavorable at the end of follow-up [-0.51 (-1.76-0.81) vs. 0.28 (-1.24-1.74), =0.20]; the similar trend was also shown for insulin sensitivity index (HOMA1-S) [2.33 (-3.59-12.46) vs. -2.33 (-10.61-9.16), =0.148]. No differences were observed in FBG, HbA1C, and hs-CRP changes between the trial groups. The current study did not support the improving effect of melatonin on glucose homeostasis.
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http://dx.doi.org/10.22037/ijpr.2019.112011.13485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393042PMC
January 2019

Serum Thyroid Peroxidase Antibody Level and Incident Hypertension in Iranian Men: A Suggestion for the Role of Thyroid Autoimmunity.

Endocr Metab Immune Disord Drug Targets 2020 ;20(10):1711-1718

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Dysfunction of the thyroid gland has profound effects on the cardiovascular system.

Objective: We aimed to explore the relation of serum thyroid peroxidase antibody (TPO-Ab), as a marker of thyroid autoimmunity with incident hypertension among a euthyroid population.

Methods: A total of 3681 participants (1647 men) entered the study. Multivariate Cox proportional hazard models were conducted to estimate the association between TPO-Ab and incident hypertension.

Results: The mean age (standard deviation) of the participants was 37.5 (12.8) years. During a median follow-up of 12.2 years, 511 men and 519 women developed hypertension. The multivariable hazard ratios (HRs) and related 95% confidence intervals (CIs) of 1-unit increase in natural logarithm (ln) of TPO-Ab for incident hypertension were 1.09 (1.00-1.19), 1.03 (0.97-1.10), and 1.05 (1.00-1.11) for men, women, and total population, respectively. Moreover, considering the TPO-Ab status as a categorical variable (i.e. TPO-Ab positive or TPO-Ab negative), the multivariate-adjusted HRs (95% CIs) of TPO-Ab positivity for incident hypertension, were 1.33 (0.95-1.85), 1.12 (0.86-1.45) and 1.19 (0.97- 1.46) for men, women, and total population, respectively.

Conclusion: Elevated serum TPO-Ab level can contribute to the development of hypertension among euthyroid men during a long follow-up; suggesting a role for thyroid autoimmunity.
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http://dx.doi.org/10.2174/1871530320666200624163035DOI Listing
January 2020

Abdominal Obesity Phenotypes and Incidence of Thyroid Autoimmunity: A 9-Year Follow-up.

Endocr Res 2020 Aug 8;45(3):202-209. Epub 2020 Apr 8.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran, IR, Iran.

Purpose: The association between obesity and autoimmune diseases has been suggested by several previous studies. The objective of our study was to assess the association of abdominal obesity phenotypes with thyroid autoimmunity.

Materials And Methods: This study was conducted within the framework of a population-based cohort study, Tehran Thyroid Study (TTS) on 4708 subjects without thyroid autoimmunity at baseline. Participants were categorized into four abdominal obesity phenotypes according to waist circumference (WC) and other metabolic syndrome components. Serum concentrations of thyroid peroxidase antibody (TPOAb), free T4 (FT4), thyrotropin (TSH), glucose, and lipid profiles were measured after 3, 6 and 9 years of follow-up. Cox proportional hazard models were used to evaluate associations of different phenotypes with the incidence of thyroid autoimmunity, adjusted for age, sex, FT4, and TSH.

Results: Highest and lowest incidence rates of TPOAb positivity were observed among metabolically unhealthy, non-abdominally obese (MUNAO) [8.78 (7.31-10.55) per 1000 person-years of follow-up] and metabolically unhealthy abdominally obese (MUAO) [4.98 (3.88-6.41) per 1000 person-years of follow-up] phenotypes. Considering the metabolically healthy non-abdominal obese (MHNAO) individuals as reference, none of metabolically healthy abdominally obese (MHAO), MUNAO, and MUAO phenotypes were associated with increased risk of developing TPOAb positivity. Compared to individuals with high WC, the incidence rate (95%CI) of TPOAb positivity was higher among those with normal WC: 8.44 (7.13-10.0) vs 5.11 (4.01-6.51) per 1000 person-years, respectively. Higher WC was not associated with incident TPOAb positivity.

Conclusion: There was no significant association between baseline abdominal obesity phenotype status and development of TPOAb positivity over 9 years of follow-up.
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http://dx.doi.org/10.1080/07435800.2020.1749847DOI Listing
August 2020

Parity and Incidence of Thyroid Autoimmunity: A Population-Based Tehran Thyroid Study.

Thyroid 2020 08 7;30(8):1186-1192. Epub 2020 May 7.

Endocrine Research Center; Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Autoimmune thyroid disease is the most common autoimmune disorder. Evidence regarding causes of the high prevalence and incidence of thyroid autoimmunity in women, and especially women of reproductive age, is still inconclusive and previous studies have suggested genetic, environmental, and existential factors to play a role in its pathogenesis. In this study, we aimed to investigate the effect of parity and other reproductive factors on the incidence of thyroid autoimmunity within the framework of the Tehran Thyroid Study (TTS). This study was conducted within the framework of the TTS and 1999 nonpregnant euthyroid thyroid peroxidase antibody (TPOAb) negative women were followed up for an average of 8.3 years. A pooled logistic regression model was used to assess the association (odds ratio) between time-dependent covariates parity, menopause, and abortion, and incidence of TPOAb positivity. The total incidence rate of TPOAb positivity was 8.65 [7.35-10.18] per 1000 person-years. We found no significant association between changes in the number of parity and risk of developing TPOAb using multiple pooled logistic models both as crude effect and after adjustment for age, body mass index, and smoking. Similarly, there was no association between changes of parity, menopause, and abortion status, and incidence of TPOAb positivity. Parity does not seem to have an independent role in triggering thyroid autoimmunity, but vast immunological and physiological changes during pregnancy may act as a precipitating factor in the context of other genetic and environmental modifiers.
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http://dx.doi.org/10.1089/thy.2019.0440DOI Listing
August 2020

Improving Prediction of Age at Menopause Using Multiple Anti-Müllerian Hormone Measurements: the Tehran Lipid-Glucose Study.

J Clin Endocrinol Metab 2020 05;105(5)

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Context: Several statistical models were introduced for the prediction of age at menopause using a single measurement of anti-müllerian hormone (AMH); however, individual prediction is challenging and needs to be improved.

Objective: The objective of this study was to determine whether multiple AMH measurements can improve the prediction of age at menopause.

Design: All eligible reproductive-age women (n = 959) were selected from the Tehran Lipid and Glucose Study. The serum concentration of AMH was measured at the time of recruitment and twice after that at an average of 6-year intervals. An accelerated failure-time model with Weibull distribution was used to predict age at menopause, using a single AMH value vs a model that included the annual AMH decline rate. The adequacy of these models was assessed using C statistics.

Results: The median follow-up period was 14 years, and 529 women reached menopause. Adding the annual decline rate to the model that included single AMH improved the model's discrimination adequacy from 70% (95% CI: 67% to 71%) to 78% (95% CI: 75% to 80%) in terms of C statistics. The median of differences between actual and predicted age at menopause for the first model was -0.48 years and decreased to -0.21 in the model that included the decline rate. The predicted age at menopause for women with the same amount of age-specific AMH but an annual AMH decline rate of 95 percentiles was about one decade lower than in those with a decline rate of 5 percentiles.

Conclusion: Prediction of age at menopause could be improved by multiple AMH measurements; it will be useful in identifying women at risk of early menopause.
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http://dx.doi.org/10.1210/clinem/dgaa083DOI Listing
May 2020

Smoking status and changes in thyroid-stimulating hormone and free thyroxine levels during a decade of follow-up: The Tehran thyroid study.

Caspian J Intern Med 2020 ;11(1):47-52

Prevention of Metabolic Disorders Research Center Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Smoking can cause thyroid disorders; the aim of the present study was to investigate the association between smoking status and changes in thyroid hormone levels among adult males during a decade long follow-up of in the Tehran Thyroid Study (TTS).

Methods: Data of 895 adult males (smokers=115, non-smokers=691, ex-smokers=89) participants of the TTS without any previously known thyroid disease were analyzed. To examine trends of changes in thyroid hormone levels in these three groups, generalized estimating equation models were used. The interaction between the smoking status and each phase of the study was checked in a separate model.

Results: Age and BMI adjusted trends of free thyroxine (FT4) demonstrated a non-significant decrease in participants (P=0.121) and thyroid-stimulating hormone (TSH) gained a significant average increase value over time in the total population (adjusted marginal mean of TSH=1.15 mU/L in phase 1, vs. 1.75 mU/L in phase 4, P<0.0001). Of the three groups, non-smokers and ex-smokers showed statistically significant increases in TSH during the follow-up period, whereas the smoker group had lower increases in TSH levels, changes from phase 1 until phase 2 among smokers were 38.46%, vs 43.54% and 52.94% in the ex and non-smokers, respectively.

Conclusion: TSH was lower and FT4 was higher in smokers compared with the other smoker groups, although TSH level shows no decreasing trend over time in this group. The increasing trend of TSH in smokers was similar to ex and non-smokers. No difference was seen in FT4 trends among the smoking groups.
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http://dx.doi.org/10.22088/cjim.11.1.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992726PMC
January 2020

Systemic Thyroid Hormone Status in Treated Graves' Disease.

Int J Endocrinol Metab 2019 Oct 12;17(4):e95385. Epub 2019 Oct 12.

Department of Epidemiology and Biostatistics, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: We aimed to compare the markers of thyroid hormone status in treated euthyroid Graves' patients and levothyroxine (LT4)-treated hypothyroid Graves' patients.

Methods: We collected the data of 277 patients, including 140 radioiodine-treated hypothyroid Graves' patients on LT4 treatment (group 1), 83 euthyroid Graves' patients on methimazole (MMI) therapy (group 2), and 54 euthyroid Graves' patients off MMI or radioiodine therapy for > 2 years (group 3). After the exclusion of diabetic patients, 130, 73, and 52 patients remained for analysis in groups 1, 2, and 3, respectively. Pearson and Spearman correlation coefficients were employed to assess the relationships between T3:T4 ratio and variables in each group along with univariate and multivariate linear regression models.

Results: The mean age and female/male ratio were similar in the three groups. Serum fT4 was significantly higher and T3, TSH, TPOAb, and TRAb were significantly lower in group 1 than in group 2 and combined groups 2 and 3, which translated to 27% lower serum T3:T4 ratio in group 1. Higher BMI, serum cholesterol, and LDL cholesterol and lower HDL cholesterol were observed in group 1 than in combined groups 2 and 3. In multivariate regression analysis, the T3:T4 ratio was significantly higher in combined groups 2 and 3 than in group 1 in the presence of BMI and serum fasting blood glucose, triglycerides, and TSH.

Conclusions: Hypothyroid Graves' patients using LT4 exhibited lower T3:T4 ratio despite lower TSH levels and their BMI and lipid parameters differed from those of euthyroid Graves' patients.
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http://dx.doi.org/10.5812/ijem.95385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942169PMC
October 2019

A comparison of the effects of oral contraceptives on the clinical and biochemical manifestations of polycystic ovary syndrome: a crossover randomized controlled trial.

Hum Reprod 2020 01;35(1):175-186

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Study Question: Do oral contraceptives (OCs) containing progestins with low androgenic or antiandrogenic activities have different effects to those containing levonorgestrel (LNG) on clinical, androgenic and metabolic manifestations of polycystic ovarian syndrome (PCOS)?

Summary Answer: The three OCs tested had similar effects on clinical findings of hyperandrogenism (HA), whereas products containing LNG were less effective on androgenic profiles and had detrimental effects on lipid profiles.

What Is Known Already: Despite data available on the effects of OCs, the superiority of products with low androgenic or antiandrogenic progesterone components in comparison with older products used in women with PCOS has not been clarified.

Study Design, Size, Duration: This study is a crossover randomized controlled six-arm trial, with all six arms including two 6-month treatment periods, one period with OCs containing LNG, and the other with one of three OCs containing desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP). The trial was conducted between February 2016 and January 2018 and enrolled 200 patients with PCOS.

Participants/materials, Setting, Methods: Two hundred women with PCOS (ages 18-45 years) were recruited at the endocrine outpatient clinic of the Research Institute for Endocrine Sciences (RIES) of the Shahid Beheshti University of Medical Sciences, Tehran, Iran. A blocking or stratification random allocation (block size = 6) using a computer-based random number generator was prepared to assign participants to treatment groups. Both the clinical examiner and data analyst were blinded to participants during the trial. Outcomes of interest, including anthropometric and clinical manifestations and hormonal, and biochemical parameters were assessed at baseline, after 3 and 6 months of each treatment and after the washout period.

Main Results And The Role Of Chance: This study detected a higher decrease in free-androgen index (FAI) levels after 3 months of treatment with OCs containing DSG (95% CI: -2.3, -1.0), CPA (95% CI: -2.4, -1.1) and DRSP (95% CI: -2.6, -1.4), compared with products containing LNG (P < 0.001). Use of OCs containing DSG (95% CI: -3.6, -1.5), CPA (95% CI: -3.1, -0.8) and DRSP (95% CI: -3.4, -1.1) for 6 months was associated with more decrease in FAI, compared with products containing LNG (P < 0.001). The study showed that use of OCs containing DSG, CPA and DRSP for 3-6 months was associated with a higher increase of sex hormone-binding globulin (SHBG), compared with products containing LNG (P < 0.001). We also observed more decrease in dehydroepiandrosterone sulfate levels after use of OCs containing DSG (P = 0.003), CPA (P = 0.012) and DRSP (P < 0.001) for 6 months, compared with products containing LNG. Our results showed that the use of OCs containing DRSP for 6 months was associated with more improvement in acne, compared with products containing LNG (P = 0.007). Women treated with OCs containing CPA, and DRSP for 3 months had higher TG and HDL levels and lower LDL levels, compared with those treated with products containing LNG (P < 0.05). After 6 months of treatment, patients treated with OCs containing DRSP had a sharper decline in LDL levels and more increase in HDL levels, compared to those treated with products containing LNG (P = 0.001).

Limitations, Reasons For Caution: Considering this trial was conducted in women diagnosed with Androgen Excess Society criteria, the results may not be generalizable for mild phenotypes diagnosed using Rotterdam criteria. Other limitations of the study include the high dropout rate, the lack of a gold standard androgen assay and the multiple end points.

Wider Implications Of The Findings: Our results support the views of clinicians, who suggest an OC with a low androgenic or antiandrogenic progestin, if available, to treat PCOS.

Study Funding/competing Interest(s): This study was supported by the RIES, Shahid Beheshti University of Medical Sciences, Tehran, Iran. There are no conflicts of interest.

Trial Registration Number: IRCT201702071281N2.

Trial Registration Date: 21 February 2017.

Date Of First Patient’s Enrolment: 21 March 2017.
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http://dx.doi.org/10.1093/humrep/dez255DOI Listing
January 2020

Impact of 3-year changes in fasting insulin and insulin resistance indices on incident hypertension: Tehran lipid and glucose study.

Nutr Metab (Lond) 2019 9;16:76. Epub 2019 Nov 9.

1Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: To examine the association between changes in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin-glucose ratio (IGR) levels, over approximately 3 years with incident hypertension.

Methods: A total of 2814 Iranian participants (1123 men) without hypertension and known diabetes at baseline and the first examination were followed for a median of 6.32 years. The associations between quartiles of changes in fasting insulin and IR indices with incident hypertension were assessed using multivariate Cox proportional hazard regression analyses with first quartile as reference. The models were adjusted for baseline values of insulin or each IR index, and age, sex, smoking, physical activity, educational levels, marital status, history of cardiovascular diseases, baseline levels of systolic and diastolic blood pressures, estimated glomerular filtration rate, triglycerides, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose (only for insulin change) and both body mass index (BMI) per se, and its change. Akaike's information criteria (AIC) was applied as indicator for goodness of fit of each predictive model. The discrimination ability of models was calculated using the Harrell's C statistic.

Results: During the study, 594 incident cases of hypertension (253 men) were identified. The 4th quartile of changes in insulin, HOMA-IR, and IGR showed hazard ratios (95% confidence interval) of 1.31 (1.01-1.69), 1.18 (0.92-1.52), and 1.53 (1.18-1.98) for hypertension, respectively, in fully-adjusted models. Changes in fasting insulin levels and IR indices showed significant increasing trends for incident hypertension, moving from 1st to 4th quartiles (all -values < 0.05). Focusing on model fitness, no superiority was found between changes in fasting insulin, HOMA-IR, and IGR to predict incident hypertension. The discriminatory powers of changes in fasting insulin and IR indices as assessed by C index were similar (i.e. about 80%).

Conclusion: Changes in fasting insulin and IR indices were significantly associated with developing hypertension among normotensive population even after considering BMI changes.
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http://dx.doi.org/10.1186/s12986-019-0402-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842481PMC
November 2019

Isolated Hypothyroxinemia in Iranian Pregnant Women, the Role of Iodine Deficiency: A Population-Based Cross-Sectional Study.

Thyroid 2020 02 20;30(2):262-269. Epub 2019 Dec 20.

Endocrine Research Center; Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Thyroid disorders such as subclinical hypothyroidism and isolated maternal hypothyroxinemia are understudied in pregnant women, despite their possible adverse effects on the health of mother and child. Also, the role of iodine deficiency in developing such disorders has not yet been fully understood. The present national population-based cross-sectional study was conducted on 1080 randomly recruited pregnant women, aged 20-40 from 12 provinces of Iran from 2013 to 2014. Serum concentrations of thyrotropin, T4, thyroid peroxidase antibody (TPOAb), and triiodothyronine (T3) resin uptake values were measured in fasting blood samples, and urinary iodine concentration (UIC) was measured in three separate urine samples. Multinomial logistic regression was run to analyze the possible risk factors regarding thyroid disorders. To clarify the role of iodine in thyroid status specifically, the determinants of UIC and its correlations with thyroid function tests were investigated independently and through subgroup analysis. Isolated hypothyroxinemia was the most common thyroid disorder (9.9%), followed by subclinical hypothyroidism (8%). In comparison to euthyroid pregnant women, isolated hypothyroxinemia was more likely in pregnant women older than 30 years (odds ratio [OR] = 1.6), in the second and the third trimesters (OR = 2.62 and 2.12 respectively), with history of multiparity (OR = 1.72), residing in rural areas (OR = 1.57) and in the capital province of the country (OR = 3.3). Subclinical hypothyroidism was more likely in TPOAb positive pregnant women (OR = 2.56). All the mentioned ORs were statistically significant ( < 0.05). The UIC did not correlate significantly with any of the thyroid function tests in the study population. Subgroup analysis showed a significant correlation between UIC and T4 in pregnant women with subclinical hypothyroidism ( < 0.05). Isolated maternal hypothyroxinemia was the most prevalent thyroid disorder in Iranian pregnant women and its associated risk factors were identified. Although the calculated prevalence of thyroid disorders was expected in a moderately iodine deficient setting, no correlations between UICs and thyroid function tests were found at the individual level. The contribution of iodine deficiency to thyroid condition for each pregnant woman may be more evident in pregnant women with certain thyroid disorders or those with long-term iodine deficiency.
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http://dx.doi.org/10.1089/thy.2019.0047DOI Listing
February 2020

Does a restricted energy low glycemic index diet have a different effect on overweight women with or without polycystic ovary syndrome?

BMC Endocr Disord 2019 Sep 2;19(1):93. Epub 2019 Sep 2.

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, Tehran, Iran.

Background: Obese women with polycystic ovary syndrome (PCOS) may face additional barriers in achieving weight loss. We aimed to compare the effects of the hypocaloric low glycemic index (LGI) diet on anthropometric variables and insulin resistance in women with and without PCOS and investigate the effect of this diet on the clinical and hormonal features of PCOS women.

Methods: This interventional study was carried out at the Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Of 108 women invited for the purpose of the present study, 62 participants (PCOS = 28, non-PCOS = 34) followed a 24-week energy restricted LGI diet. Anthropometric, biochemical, hormonal and clinical measurements were documented at baseline, 12 weeks and 24 weeks with intervention.

Results: The percentages of weight loss achieved by both the PCOS and non-PCOS groups did not differ significantly (PCOS: -8.04% vs. non-PCOS: -8.09%). No significant difference in decrease of homeostatic model assessment of insulin resistance (HOMA-IR) was observed between the two groups (PCOS = - 0.83 ± 0.33, non PCOS = - 0.79 ± 0.28, P = 0.83). In PCOS women, significant reduction in total testosterone (- 0.91 ± 0.33 nmol/L, P = 0.006), FAI (- 4.47 ± 1.1, P < 0.001) and increase in SHBG (38.98 ± 11.02 nmol/L, P < 0.001) were observed. Menstrual irregularity was improved in 80% of women with PCOS and a significant decrease (32.1%) in occurrence of acne was reported.

Conclusions: This diet has equally beneficial effects on anthropometric and metabolic characteristics of overweight women with and without PCOS.

Trial Registration: This study is registered in the Iranian Randomized Clinical Trials Registry (IRCT, code: IRCT2016092129909N1 ).
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http://dx.doi.org/10.1186/s12902-019-0420-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720418PMC
September 2019

Effect of phlebotomy versus oral contraceptives containing cyproterone acetate on the clinical and biochemical parameters in women with polycystic ovary syndrome: a randomized controlled trial.

J Ovarian Res 2019 Aug 30;12(1):78. Epub 2019 Aug 30.

Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Parvane Street, Yaman Street, Velenjak, P.O.Box: 19395-4763, Tehran, Iran.

Background: Reduction of the body iron stores can improve hyperandrogenemia and insulin resistance. This study aimed to compare clinical and para-clinical responses to the treatment of phlebotomy using oral contraceptive pills (OCs) containing cyproterone acetate in women with PCOS.

Methods: In this randomized clinical trial, 64 patients with PCOS were randomly assigned to the phlebotomy and OCs groups (n = 32 in each group). The intervention group, using a single treatment procedure, underwent venesection of 450 mL of whole blood at the early follicular phase of the spontaneous or progesterone-induced menstrual cycle. The control group received OCs pills for 3 months from the 1th day of spontaneous or progesterone-induced menstrual cycle onwards for 3 weeks, followed by a pill-free interval of 7 days. The women were evaluated after the 3-month intervention. The primary outcome measure was a change in the HOMA-IR and free androgen index (FAI). Secondary outcomes were changes in the Ferriman-Gallwey (FG) score and other clinical, biochemical and hormonal changes from the baseline (pre-treatment) to week 12.

Results: In the phlebotomy group, 27 (84.3%) and in the OCs group 30 (93.7%) of the women completed the 3-month follow-up. The median HOMA-IR significantly decreased from 3.5 to 2.7 in the phlebotomy, and from 3.1 to 2.8 in the OCs group, and the changes were comparable between the groups. Median changes in the FAI significantly decreased in both groups, but the differences were not statistically significant between the groups (P = 0.061). With regard to secondary outcomes, mean FG scores in both groups significantly decreased [from 16.8 (6) to 13.3 (7.4), P < 0.028] in the phlebotomy group and [from 14.3 (7) to 9.8 (7.6) in the OCs group, P = 0.001] after 3 months of treatment, but such changes had no statistically significant differences between the groups. During treatment, menstrual cycles became regular in all women in the OCs group and in 12.27 (44.4%) of the women in the phlebotomy group, and the difference was statistically significant (P = 0.001). Despite no statistically significant differences in lipid profiles between the groups at the baseline, triglycerides were significantly higher in the OCs group compared to the phlebotomy at end of follow up (p = 0.019).

Conclusion: Both treatment modalities had similar beneficial effects on insulin resistance and on androgenic profiles. However, OCs was reported more effective in treating menstrual irregularities and phlebotomy had less adverse effects on triglyceride concentrations.

Trial Registration: Code: IRCT2013080514277N1 .
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http://dx.doi.org/10.1186/s13048-019-0554-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716867PMC
August 2019

Maternal Urinary Iodine Concentration and Pregnancy Outcomes: Tehran Thyroid and Pregnancy Study.

Biol Trace Elem Res 2020 Apr 27;194(2):348-359. Epub 2019 Jul 27.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Iodine is essential for the production of thyroid hormones, and its deficiency during pregnancy may be associated with poor obstetric outcomes. The aim of this study was to investigate the relationship between maternal iodine statuses with pregnancy outcomes among pregnant Iranian women, considering their baseline thyrotropin (TSH) status. We used data from the Tehran Thyroid and Pregnancy Study (TTPS), a two-phase population-based study carried out among pregnant women receiving prenatal care. By excluding participants with overt thyroid dysfunction and those receiving levothyroxine, the remaining participants (n = 1286) were categorized into four groups, according to their urine iodine status: group 1, urine iodine concentration (UIC) < 100 μg/L; group 2, UIC between 100 and 150 μg/L; group 3, UIC between 150 and 250 μg/L; and group 4, UIC ≥ 250 μg/L. Primary outcome was preterm delivery. Preterm delivery occurred in 29 (9%), 19 (7%), 15 (5%), and 8 (4%) women, and neonatal admission was documented in 22 (7%), 30 (12%), 28 (11%), and 6 (3%) women of groups 1, 2, 3, and 4, respectively. Generalized linear regression model (GLM) demonstrated that the odds ratio of preterm delivery was significantly higher in women with urinary iodine < 100 μg/L and TSH ≥ 4 μIU/mL than those with similar urinary iodine with TSH < 4 μIU/mL (OR 2.5 [95% CI 1.1, 10], p = 0.024). Adverse pregnancy outcomes are increased among women with UIC < 100 μg/L, with serum TSH concentrations ≥ 4 μIU/mL.
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http://dx.doi.org/10.1007/s12011-019-01812-5DOI Listing
April 2020

Increased Remission Rates After Long-Term Methimazole Therapy in Patients with Graves' Disease: Results of a Randomized Clinical Trial.

Thyroid 2019 09 28;29(9):1192-1200. Epub 2019 Aug 28.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Studies differ regarding whether, compared with courses of conventional duration, longer-term antithyroid drug treatment increases frequency of remission in patients with Graves' hyperthyroidism. We prospectively conducted a randomized, parallel-group study comparing relapse rates in patients receiving longer-term versus conventional-length methimazole therapy. We also sought variables associated with relapse following the latter. We enrolled 302 consecutive patients with untreated first episodes of Graves' hyperthyroidism. After 18-24 months of methimazole, 258 patients (85.4%) were randomized to an additional 36-102-month courses ("long-term group":  = 130; scheduled total time on methimazole: 60-120 months) or discontinuation of methimazole ("conventional group":  = 128). Patients were followed 48 months postmethimazole cessation. We performed Cox proportional hazards modeling to identify factors associated with relapse after conventional courses. Methimazole was given for 95 ± 22 months in long-term patients and 19 ± 3 months in the conventional group. Fourteen patients experienced cutaneous reactions and 2 liver enzyme elevations during the first 18 months of treatment; no further methimazole-related reactions were observed despite therapy for up to another 118 months. Hyperthyroidism recurred within 48 months postmethimazole withdrawal in 15% (18/119) of long-term patients versus 53% (65/123) of conventional group patients. In the conventional group, older age, higher triiodothyronine or thyrotropin receptor antibody concentrations, lower thyrotropin concentration, or possession of the rs1879877 polymorphism or the polymorphism were independently associated with relapse. Administration of low-dose methimazole for a total of 60-120 months safely and effectively treats Graves' hyperthyroidism, with much higher remission rates than those attained by using conventional 18-24-month courses.
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http://dx.doi.org/10.1089/thy.2019.0180DOI Listing
September 2019

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

Horm Metab Res 2019 Jun 17;51(6):347-352. Epub 2019 Jun 17.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, I. R. Iran.

Various cut-offs have been proposed for thyroid peroxidase antibodies (TPOAb) positivity. Considering that the long-term trend of TPOAb levels and its positivity incidence is not clearly understood, we conducted the current study to determine the longitudinal variations of TPOAb in a population-based cohort study. We followed 5783 individuals of Tehran Thyroid cohort Study (TTS) for 10 years (4 phases). After exclusions, data of 3493 euthyroid participants remained for analyses. The baseline prevalence rates of TPOAb positivity were 19.8, 17, and 11.4% and the annual incidence rates (95% CI) of TPOAb positivity were 8.53 (8.29-8.77), 7.59 (7.37-7.80) and 6.79 (6.60-6.98) per 1000 persons for the 3 proposed cut-offs of 14.77, 18.38, and 40 U/l; respectively. Although a slightly increasing trend was observed for TPOAb levels (p=0.001) and its conventional positivity (TPOAb>40U/l), the recently proposed cut-offs of 14.77 and 18.38 U/l showed constant TPOAb positivity over 10 years. The time trends of the TPOAb levels among younger participants were significantly different from older participants (time×age effect p=0.004), with the former having an increasing trend and the latter, a relatively decreasing trend. Although the prevalence of TPOAb positivity was significantly (p<0.001) higher among women as compared to men, the longitudinal changes of TPOAb were similar in men and women. TPOAb positivity along with TSH values between 2.5 and 5.0 mU/l or free T4 values between 0.93 and 1.7 ng/dl exerted a significantly increased risk of subclinical or overt hypothyroidism. In an iodine sufficient population, an increasing trend in TPOAb levels was observed in line with the increasing incidence of subclinical and overt hypothyroidism.
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http://dx.doi.org/10.1055/a-0887-6213DOI Listing
June 2019

Trend of lipid and thyroid function tests in adults without overt thyroid diseases: A cohort from Tehran thyroid study.

PLoS One 2019 16;14(5):e0216389. Epub 2019 May 16.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Context: While the role of overt hypothyroidism in lipid disorders is clear, the association between dyslipidemia and subclinical thyroid diseases remains unclarified.

Objective: To examine lipid trends based on thyroid function over a 10-year period.

Design: This is a prospective population based cohort study.

Setting: General community.

Participants: 2383 euthyroid participants, as well as those with subclinical thyroid diseases, in all residents of district 13 of Tehran were examined. Subjects who were on levothyroxine, anti-hyperthyroid drugs, and glucocorticoids, those with a history of thyroid surgery or RAI and pregnant women were excluded.

Main Outcome Measures: Lipid trends in Model 1 were adjusted for age and follow up duration, and in Model 2 gender-specific multivariate adjustments were performed for thyroid status, diabetes mellitus, smoking status, education, BMI, lipid lowering medications, age and follow up duration by using generalized estimating equations.

Results: In every four years of assessments, there were significant decreases in levels of all lipid parameters (all Ps <0.001) except for HDL-C, in which a decrescendo-crescendo trend was observed. The results did not change after adjusting for thyroid status, consumption of lipid lowering drugs during the follow-up period, or other variables. There were significant decreases in the prevalence of hypercholesterolemia and hypertriglyceridemia (all Ps <0.001) during the follow-up period.

Conclusion: During a 10 year follow-up, decrescendo trends were observed in levels of total cholesterol, triglycerides, which were not be accounted for by the consumption of lipid lowering drugs and thyroid status.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216389PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522003PMC
January 2020

Overtime trend of thyroid hormones and thyroid autoimmunity and ovarian reserve: a longitudinal population study with a 12-year follow up.

BMC Endocr Disord 2019 May 7;19(1):47. Epub 2019 May 7.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Ovarian reserve, vital for reproductive function, can be adversely affected by thyroid diseases. Despite alternations of thyroid hormones with ageing, data on interactions between the overtime trend of thyroid functions and ovarian reserve status has rarely been reported. We aimed to examine the overtime trend of thyroid hormones, thyroid peroxidase antibody (TPO Ab) and their associations with ovarian reserve status, identified by levels of age specific anti-mullerian hormone (AMH) in reproductive aged women, who participated in 12-year cohort of Tehran Thyroid Study (TTS).

Methods: Reproductive age women(n = 775) without any thyroid disease or ovarian dysfunction were selected from the Tehran Thyroid Study cohort. Participants were divided into four age specific AMH quartiles (Q1-Q4), Q1, the lowest and Q4, the highest. AMH was measured at the initiation of study and thyroid stimulating hormone (TSH), free T4 (FT4), and TPO Ab were measured at baseline and at three follow up visits.

Results: At baseline, there was no statistically significant difference in thyroid hormones between women of the four quartiles, although TPO Ab levels were higher in women of Q1. During the follow ups, FT4 was decreased in all quartiles (p < 0.05), whereas TPO Ab increased in Q1 (p = 0.02). Odds ratio of overall TPO Ab positivity in women of Q1 was 2.08 fold higher than those in Q4. (OR: 2.08, 95%CI: 1.16, 3.72; p = 0.01).

Conclusion: Women with the lowest ovarian reserves had higher levels of TPO Ab, with a positive trend of this antibody overtime in comparison to other quartiles, indicating that this group may be at a higher risk of hypothyroidism over time.
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http://dx.doi.org/10.1186/s12902-019-0370-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505305PMC
May 2019

High prevalence of benign mammary tumors in a rat model of polycystic ovary syndrome during postmenopausal period.

Gynecol Endocrinol 2019 Aug 16;35(8):679-684. Epub 2019 Apr 16.

a Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. Significant associations between PCOS and benign breast diseases (BBD) and a possibly potential association between PCOS and breast cancer have been reported. The etiology of these events of mammary glands in PCOS remains unclear. Animal models that show BBD and breast cancer may contribute to further understanding about these diseases. We aimed to examine the spontaneous occurrence of mammary tumors, their prevalence, and type in our rat model of PCOS. Prenatal androgen-induced PCOS rats and controls were examined in later life. Benign mammary tumors were observed in 75% and 33.33% of PCOS rats and controls during the postmenopausal period, respectively ( = .0158). Mammary tumors were non-invasive, margins of excision were normal and tumors were freely movable, in both groups. After microscopic evaluations of tumors, proliferative breast lesions and adenomas with a tubular growth pattern were observed in both groups. However, in PCOS rats, of benign tumors two had a mixed pattern of fibroadenoma/fibroma and cysts. High prevalence of benign mammary tumors was observed in our rat model of PCOS during the postmenopausal period, possibly due to hormonal imbalances during their reproductive lifespan; this model may contribute to current data available regarding the events of mammary glands in PCOS.
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http://dx.doi.org/10.1080/09513590.2019.1576613DOI Listing
August 2019

Effect of long-term sodium nitrate administration on diabetes-induced anemia and glucose homeostasis in obese type 2 diabetic male rats.

Nitric Oxide 2019 05 14;86:21-30. Epub 2019 Feb 14.

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences. Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Purpose: Anemia is common in patients with type 2 diabetes. This aims at determining long-term effects of nitrate administration on diabetes-induced anemia in obese type 2 diabetic rats.

Methods: Male Wistar rats were divided into 4 groups: Control, control + nitrate, diabetes, and diabetes + nitrate. Type 2 diabetes was induced using high-fat diet followed by injection of streptozotocin (30 mg/kg). Sodium nitrate (100 mg/L in drinking water) was administered for six months. After overnight fasting, levels of glucose and erythropoietin (EPO) and complete blood cell count (CBC) were measured at month 0, month 3, and month 6. At month 6, serum iron, and testosterone as well as EPO protein levels and hypoxia-inducible factor-1 (HIF-1) mRNA levels in kidney and liver were measured.

Results: Nitrate administration decreased serum glucose in diabetic rats by 10% and 15% at months 3 and 6, respectively. Nitrate restored decreased red blood cells count, hemoglobin concentration, and hematocrit to control levels in diabetic rats; in addition, nitrate restored decreased serum, kidney, and liver EPO levels to near normal values. Nitrate also increased HIF-1 mRNA levels in both kidney and liver of diabetic rats. Diabetic rats had lower serum testosterone (37%) and iron (20%) and nitrate restored these parameters to near normal values.

Conclusion: Long-term and low dose of nitrate had beneficial effects against anemia in obese type 2 diabetic rats; these effects were associated with increased EPO and HIF-1 levels in kidney and liver as well as increased circulating EPO, testosterone, and iron.
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http://dx.doi.org/10.1016/j.niox.2019.02.003DOI Listing
May 2019

Association of circulating 25-hydroxyvitamin D and parathyroid hormone with carotid intima media thickness in children and adolescents with excess weight.

J Steroid Biochem Mol Biol 2019 04 31;188:117-123. Epub 2018 Dec 31.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Evidence on the association of vitamin D and parathyroid hormone (PTH) with cardiovascular risk factors in the young is limited. We therefore assessed the relationships of circulating vitamin D and PTH concentrations and subclinical atherosclerosis in overweight or obese children and adolescents. This was a cross-sectional study, investigated the association of 25-hydroxyvitamin D (25(OH)D), intact PTH (iPTH), and iPTH/25(OH)D ratio with carotid intima-media thickness (cIMT) in 368 Iranian children and adolescents with a body mass index (BMI) ≥1 z-score based on WHO criteria. Ultrasound measurement of cIMT was performed. Multivariable linear and logistic regressions were used to test associations between 25(OH)D, iPTH, and iPTH/25(OH)D ratio using one-ln-unit increment with cIMT. Median (25-75 interquartile range) 25(OH)D and iPTH concentrations were 11.8 (8.2-18.6) ng/ml and 38.2 (25.0-61.4) pg/ml, respectively. Among boys, each one-ln-unit increase of iPTH and iPTH/25(OH)D ratio was significantly associated with 0.194 mm and 0.147 mm increase, respectively, in cIMT, after adjustment for confounders. A similar pattern of association was observed between iPTH (β = 0.143, p = 0.037) and iPTH/25(OH)D ratio (β=0.172, p = 0.007) with cIMT among obese participants. Furthermore, among obese participants in the fully adjusted model, each one-ln-unit increase of iPTH and 25(OH)D/iPTH ratio was significantly associated with 53% and 39% increased odds of having high cIMT, respectively. Girls and those who were overweight did not show any significant association of 25(OH)D, iPTH, and iPTH/25(OH)D ratio with cIMT. High iPTH and iPTH/25(OH)D ratio were associated with increased cIMT in boys and those who are obese.
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http://dx.doi.org/10.1016/j.jsbmb.2018.12.015DOI Listing
April 2019

Diabetes Mellitus: Findings from 20 Years of the Tehran Lipid and Glucose Study.

Int J Endocrinol Metab 2018 Oct 16;16(4 Suppl):e84784. Epub 2018 Oct 16.

Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Context: We summarized findings from Tehran lipid and glucose study (TLGS) about different aspects of type 2 diabetes (T2D) over the span of nearly 2 decades.

Evidence Acquisition: A review was undertaken to retrieve papers related to all aspects of T2D from the earliest date available up to January 30, 2018.

Results: An annual crude incidence rate of 10 per 1000 person-years of follow-up was found for T2D in adult participants. Overall incidence rate of pre-diabetes/T2D was 36.3 per 1000 person-years or about 1% each year among youth. Diabetes was associated with increased risk of CVD [hazard ratio (HR): 1.86, 95% confidence interval (95% CI): 1.57 - 2.27] and mortality [HR: 2.56; 95% CI: 2.08 - 3.16] in the total population. Compared with non-diabetic men and women, their diabetic counterparts survived 1.4 and 0.7 years shorter, respectively, during 15 years of follow-up. Wrist circumference, hyperinsulinaemia, 25-hydroxy vitamin D and increase in alanin aminotranferase provided incremental prognostic information beyond the traditional risk factors for incident T2D in adults. Using decision tree algorithms, a number of high risk groups were found for incident T2D. A probability of 84% was found for incidence of T2D among a group of men with fasting plasma glucose (FPG) > 5.3 mmol/L and waist to height ratio (WHtR) > 0.56, and women with FPG > 5.2 mmol/L and WHtR > 0.56.

Conclusions: Original TLGS studies have contributed greatly to clarify important evidence regarding the epidemiology and risk factors for T2D among Iranian population.
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http://dx.doi.org/10.5812/ijem.84784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289292PMC
October 2018