Ladan Mehran

Verified email at endocrine.ac.ir

Shahid Beheshti University of Medical Sciences,
Research Institute for Endocrine Science



                               

http://researchid.co/lmehran

EDUCATION

MD,PhD

RESEARCH INTERESTS

Epidemiology, thyroid, iodine deficiency, metabolic syndrome

53

Scopus Publications

1122

Scholar Citations

21

Scholar h-index

37

Scholar i10-index

Scopus Publications

  • Parity and incidence of thyroid autoimmunity: A population-based tehran thyroid study
    Miralireza Takyar, Maryam Rahmani, Atieh Amouzegar, Elham Madreseh, Maryam Tohidi, Ladan Mehran, and Fereidoun Azizi

    Thyroid, ISSN: 10507256, eISSN: 15579077, Pages: 1186-1192, Published: August 2020 Mary Ann Liebert Inc
    INTRODUCTION Autoimmune thyroid disease (AITD) is the most common autoimmune disorder. Evidence regarding high prevalence and incidence of thyroid autoimmunity in women, and specially women of reproductive age, is still inconclusive and previous studies have suggested genetic, environmental, and existential factors to play a role in it s pathogenesis. In this study, we aimed to investigate the effect of parity and other reproductive factors on incidence of thyroid autoimmunity within the framework of the Tehran Thyroid Study. MATERIAL AND METHODS The present study was conducted within the framework of the Tehran Thyroid Study (TTS) and 1999 non pregnant euthyroid TPOAb negative women were followed up for an average of 8.3 years. 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. RESULTS Total incidence rate of TPOAb positivity were of 8.65(7.35,10.18) per1000 person-year. 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, BMI and smoking; similarly, there was no association between changes of parity, menopause and abortion status and incidence of TPOAb positivity. CONCLUSION 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 context of other genetic and environmental etiologies.

  • Isolated Hypothyroxinemia in Iranian Pregnant Women, the Role of Iodine Deficiency: A Population-Based Cross-Sectional Study
    Ali Etemadi, Atieh Amouzegar, Ladan Mehran, Maryam Tohidi, Fereidoun Azizi, Kamyar Moradi, and Hossein Delshad

    Thyroid, ISSN: 10507256, eISSN: 15579077, Pages: 262-269, Published: February 2020 Mary Ann Liebert Inc
    Objective 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. Design 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. Method Serum concentrations of TSH, T4, thyroid peroxidase antibody and T3 resin uptake values were measured in fasting blood samples, and urinary iodine concentration was measured in three separate urine samples. Multinomial logistic regression was run to analyze the possible risk factors regarding thyroid disorders. In order 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. Results 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 over 30 years old (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 thyroid peroxidase positive pregnant women (OR=2.56). All the mentioned odds ratios were statistically significant (p<0.05). 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 (p<0.05). Conclusion 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 expectable in a moderately iodine deficient setting, no correlations between presenting urinary iodine concentrations and thyroid function tests were found at the individual level. Maybe the contribution of iodine deficiency to thyroid condition for each pregnant women is more evident in pregnant women with certain thyroid disorders or those with long term iodine deficiencies.

  • LT4 and slow release T3 combination: Optimum therapy for hypothyroidism?
    Fereidoun Azizi, Atieh Amouzegar, Ladan Mehran, and Hengameh Abdi

    International Journal of Endocrinology and Metabolism, ISSN: 1726913X, eISSN: 17269148, Published: 2020 Kowsar Medical Institute
    Context Levothyroxine (LT4) is recommended as replacement therapy for thyroid hormone deficiency. However, some hypothyroid patients receiving LT4 therapy do not feel as well as healthy subjects. This article aimed to review current knowledge regarding LT4 monotherapy versus LT4+LT3 combination therapy and propose future directions regarding LT4+slow release T3 combination treatment for hypothyroidism. Evidence Acquisition We searched PubMed and Scopus using related keywords. Results The LT4 monotherapy causes higher serum free T4 (fT4), subnormal serum free T3 (fT3), and fT3/fT4 ratio in one-fourth of patients. The LT4+LT3 combination therapy increases serum T3 and fT3 concentrations and may normalize the fT3/fT4 ratio. However, the primary outcomes, including thyroid hormone deficiency, anxiety, depression, and quality of life, may not be better in LT4+LT3 combination therapy than in LT4 monotherapy. Recent surveys show that combination therapy is on the rise, in particular, due to patient demand. The LT4 plus slow-release LT3 preparation has shown promising results in improving serum thyroid hormone concentrations. Conclusions The beneficial effect of LT4+LT3 combination therapy is not clear, and the safety of long-term therapy is yet under question. More scientific well-designed research projects are required in this field.

  • Serum thyroid peroxidase antibody level and incident hypertension in Iranian men: A suggestion for the role of thyroid autoimmunity
    Maryam Tohidi, Aidin Baghbani-Oskouei, Atieh Amouzegar, Ladan Mehran, Fereidoun Azizi, and Farzad Hadaegh

    Endocrine, Metabolic and Immune Disorders - Drug Targets, ISSN: 18715303, eISSN: 22123873, Pages: 1711-1718, Published: 2020 Bentham Science Publishers Ltd.
    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.

  • Smoking status and changes in thyroid-stimulating hormone and free thyroxine levels during a decade of follow-up: The Tehran thyroid study
    Hoda Kadkhodazadeh, Atieh Amouzegar, Ladan Mehran, Safoora Gharibzadeh, Fereidoun Azizi and Maryam Tohidi

    Caspian Journal of Internal Medicine, ISSN: 20086164, eISSN: 20086172, Pages: 47-52, Published: 2020
    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.

  • Thyroid disease and the metabolic syndrome
    Ladan Mehran, Atieh Amouzegar, and Fereidoun Azizi

    Current Opinion in Endocrinology, Diabetes and Obesity, ISSN: 1752296X, eISSN: 17522978, Pages: 256-265, Published: 1 October 2019 Ovid Technologies (Wolters Kluwer Health)
    PURPOSE OF REVIEW To summarize recent developments in the association of thyroid function with metabolic syndrome (MetS). RECENT FINDINGS Although thyroid hormones even within low normal range are associated with various metabolic abnormalities, the risk of MetS remains a controversial issue. Hyperthyroid state might be associated only with insulin resistance and dysglycemia. Autoimmune thyroid diseases may be a potential risk factor for metabolic abnormalities even in those with low normal thyroid function. SUMMARY The interrelation between thyroid stimulating hormone, free T3, freeT4 and metabolic parameters is complex and might be affected by age, sex, BMI, insulin resistance, smoking, iodine intake and inflammatory markers.

  • Audit of the congenital hypothyroidism screening program in 15 Provinces of Iran
    Archives of Iranian Medicine, ISSN: 10292977, eISSN: 17353947, Pages: 310-317, Published: June 2019

  • Evaluation of the congenital hypothyroidism screening programme in Iran: A 3-year retrospective cohort study
    Ladan Mehran, Davood Khalili, Shahin Yarahmadi, Hossein Delshad, Yadollah Mehrabi, Atieh Amouzegar, Nasrin Ajang, and Fereidoun Azizi

    Archives of Disease in Childhood: Fetal and Neonatal Edition, ISSN: 13592998, eISSN: 14682052, Volume: 104, Pages: F176-F181, Published: March 2019 BMJ
    ObjectiveTo evaluate the newborn screening programme for congenital hypothyroidism (CH) in Iran from diagnosis to management and follow-up for 3 years from 2011 to 2014.DesignRetrospective cohort.Setting and patientsSeventeen university districts were randomly selected from 30 provinces. Central data in each district were gathered and collectively analysed. Congenital hypothyroid subjects were followed for 3 years.Main outcome measuresProgramme coverage, screening and treatment age, recall rate, compliance to follow-ups.ResultsThe total number of births in 2011 was 501 726, of which 452 918 neonates (90.3%) were screened and 15 671 (3.46%) were recalled; 1085 (1:462, 0.22%) were confirmed as having CH (57.1%: permanent, 42.9%: transient) and followed for 3 years. Positive predictive value (PPV) for the first screening test was 6.9%. After the second screening, recall rate was reduced to 0.69% and PPV increased to 31.3%. Median age at screening was 6 (3–9) days and for 90.6% of patients treatment was initiated before 40 days of age with a median levothyroxine dosage of 25 µg/day; 131 (13.4%) were lost to follow-up. Mean number of follow-up visits over 3 years was 5.7 (95% CI 5.5 to 5.9) and 23% (n=225) had total compliance to all follow-ups. Median time for thyroid stimulating hormone normalisation was 45 days, 95% CI (41.1 to 48.8).ConclusionIn Iran, despite well-established protocols of screening and detecting CH subjects, stricter implementation of a structured system for monitoring and surveillance is needed to promote the management of patients and to reduce rates of loss to follow-up. Determining and addressing the causes of high false positive rates must be prioritised.

  • Long-Term Variations of Antithyroperoxidase Antibodies and its Clinical Significance
    Masoumeh Keyhanian, Farzaneh Sarvghadi, Ladan Mehran, Atieh Amouzegar, Maani Beigy, Maryam Tohidi, and Fereidoun Azizi

    Hormone and Metabolic Research, ISSN: 00185043, eISSN: 14394286, Pages: 347-352, Published: 2019 Georg Thieme Verlag KG
    AbstractVarious 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.

  • Secondary and tertiary preventions of thyroid disease
    Fereidoun Azizi, Ladan Mehran, Farhad Hosseinpanah, Hossein Delshad, and Atieh Amouzegar

    Endocrine Research, ISSN: 07435800, eISSN: 15324206, Pages: 124-140, Published: 3 April 2018 Informa UK Limited
    INTRODUCTION Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impact of illness. METHODS All articles related to secondary and tertiary prevention of thyroid diseases were reviewed. Using related key words, articles published between 2001 and 2015 were evaluated, categorized, and analyzed. RESULTS In secondary prevention, congenital hypothyroidism and subclinical hypo and hyperthyroidism are equally important. Routine screening of patients with multinodular goiter by either ultrasonography or calcitonin is a controversial issue, while calcitonin assessments in medullary cancer and RET in family members are recommended. Screening of thyroid disease in pregnancy is limited to those with risk factors. Views regarding the importance of thyroid autoimmunity in secondary prevention are also presented. In tertiary prevention, prescribing excessive doses of levothyroxine, in the elderly in particular and appropriate care of all patients to avoid progression and complications are the key issues. CONCLUSION Optimization of management of thyroid diseases requires timely screening, prevention of progression to more sever disease, optimal medical care, and avoidance of iatrogenic conditions.

  • Subclinical thyroid dysfunction and incident cardiovascular disease: Tehran thyroid study
    Iranian Journal of Endocrinology and Metabolism, ISSN: 16834844, eISSN: 16835476, Pages: 1-9, Published: April-May 2018

  • Associations between Thyroid and Blood Pressure in Euthyroid Adults: A 9-Year Longitudinal Study
    Hengameh Abdi, Safoora Gharibzadeh, Erfan Tasdighi, Atieh Amouzegar, Ladan Mehran, Maryam Tohidi, and Fereidoun Azizi

    Hormone and Metabolic Research, ISSN: 00185043, eISSN: 14394286, Pages: 236-241, Published: 1 March 2018 Georg Thieme Verlag KG
    AbstractLongitudinal studies considering associations between thyroid function in the reference range (RR) with blood pressure (BP) are scarce and contradictory. We aimed to investigate the associations of serum thyrotropin (TSH) and free T4 (FT4) with different components of BP also incident prehyperetension (preHTN) and HTN during a 9-year follow-up. A sum of 2282 euthyroid individuals from an ongoing population-based cohort study were selected. A sex-stratified multivariate generalized estimating equation (GEE) method was employed. Moreover, a multivariate transitional model was used considering preceding BP status as a predictor of dichotomous outcomes of preHTN and HTN. Multivariate-adjusted GEE analysis revealed a decreasing trend for systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP) throughout the study period in both men and women, either adjusted for serum TSH or FT4 levels. Serum FT4 within the RR was positively associated with all BP parameters in total population and in men, but serum TSH had a statistically significant mild increasing effect only on SBP, DBP and MAP of men. Multivariate transitional model found no association between serum TSH levels within the reference range (RR) and BP status; regarding serum FT4, a 1 ng/dl higher FT4 was associated with 40% increased risk of preHTN [OR (95% CI), 1.40 (1.02–1.90)], but not with HTN [OR (95% CI), 0.93 (0.80–1.09)]. It is concluded that serum FT4 within the RR is more strongly associated with BP parameters compared to TSH. This association is not consistent between men and women. Moreover, higher FT4 is associated with increased risk of preHTN.

  • Tehran thyroid study (TTS)
    Atieh Amouzegar, Ladan Mehran, Miralireza Takyar, Hengameh Abdi, and Fereidoun Azizi

    International Journal of Endocrinology and Metabolism, ISSN: 1726913X, eISSN: 17269148, Published: 2018 Kowsar Medical Institute
    Context This review summarizes key findings of the Tehran thyroid study (TTS), a large scale community-based study with approximately a two decade follow-up, about the incidence, prevalence, and natural course of thyroid disorders as well as associations between thyroid diseases and metabolic syndrome (MetS), dysglycemia, and cardiovascular disease (CVD). Evidence Acquisition PubMed, Scopus, and Web of Science databases, and the library of Research Institute for Endocrine Sciences were used to search for TTS articles. Articles were subdivided based on the fields of prevalence, incidence and natural course, and associations of thyroid function with the incident hypertension (HTN), MetS and CVDs. Results The 2.5th and 97.5th percentiles of serum thyrotropin (TSH) were 0.32 and 5.06 mU/L, respectively. Estimated reference intervals (2.5th and 97.5th percentiles) for thyroid peroxidase antibody (TPOAb) levels were 1.5 - 32.8 and 2.1 - 35 IU/mL in men and women, respectively. Euthyroid persistency was 93.24% during 6 years. There was a negative association between free thyroxine (FT4) levels and insulin resistance. Decreasing FT4 values over time would predict MetS in euthyroid and subclinical hypothyroid subjects (TSH < 10 mU/L). The incidence of thyroid disorders in patients with diabetes, pre-diabetes and healthy controls was 14, 18, and 21 per 1000 person-years, respectively, indicating significantly lower incidence in individuals with diabetes compared to healthy controls. Serum FT4 within the reference range was positively associated with all blood pressure (BP) measures in the total population and in men; however, serum TSH was positively associated with only systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure of men. No associations were found between various states of thyroid function and prevalence and incidence of CVD. Conclusions A well designed cohort study aimed to investigate the gap in knowledge regarding thyroid disorders can generate many hypotheses to be examined in randomized controlled trials.

  • Thyroid Dysfunction States and Incident Cardiovascular Events: The Tehran Thyroid Study
    Maryam Tohidi, Arash Derakhshan, Samaneh Akbarpour, Atieh Amouzegar, Ladan Mehran, Aidin Baghbani-Oskouei, Fereidoun Azizi, and Farzad Hadaegh

    Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, eISSN: 14394286, Published: 1 January 2018 Georg Thieme Verlag KG
    The objective of the study was to investigate the relation of different thyroid function states with the incidence of cardiovascular disease (CVD)/coronary heart disease (CHD) among a Middle-Eastern population with a high incidence of CVD/CHD. A total of 3975 participants entered the study (43.6% men). According to their thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels, the participants were categorized into 5 groups: euthyroid, subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism. Multivariable Cox proportional hazard models were used to assess the relation of different thyroid function states with incident CVD/CHD, with euthyroid state as reference. The mean age (SD) of the participants was 46.5 (12.0) years. At baseline, no significant difference was observed in the frequency of prevalent CVD cases (n=201) between all groups. No significant interaction was found between prevalent CVD and different thyroid function states with outcomes, hence, we did not exclude participants with prevalent CVD from data analysis. A total of 400 CVD events (358 CHD cases) during a median follow-up of 11.2 years (inter-quartile range: 1.96) occurred. During the follow-up, even in the age and sex adjusted model, no association was observed between different states of thyroid dysfunction and incidence of CVD/CHD. The multivariable hazard ratios (95% CI) of subclinical hypothyroidism, hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism for CVD events were 1.21 (0.77–1.88), 0.76 (0.33–1.69), 0.81 (0.46–1.41) and 1.48 (0.70–3.16), respectively. Both at baseline and during follow-up, no relation was observed between different states of thyroid function with prevalence and incidence of CVD/CHD.

  • Thyroid Dysfunction States and Incident Cardiovascular Events: The Tehran Thyroid Study
    Maryam Tohidi, Arash Derakhshan, Samaneh Akbarpour, Atieh Amouzegar, Ladan Mehran, Aidin Baghbani-Oskouei, Fereidoun Azizi, and Farzad Hadaegh

    Hormone and Metabolic Research, ISSN: 00185043, eISSN: 14394286, Pages: 37-43, Published: 1 January 2018 Georg Thieme Verlag KG
    AbstractThe objective of the study was to investigate the relation of different thyroid function states with the incidence of cardiovascular disease (CVD)/coronary heart disease (CHD) among a Middle-Eastern population with a high incidence of CVD/CHD. A total of 3975 participants entered the study (43.6% men). According to their thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels, the participants were categorized into 5 groups: euthyroid, subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism. Multivariable Cox proportional hazard models were used to assess the relation of different thyroid function states with incident CVD/CHD, with euthyroid state as reference. The mean age (SD) of the participants was 46.5 (12.0) years. At baseline, no significant difference was observed in the frequency of prevalent CVD cases (n=201) between all groups. No significant interaction was found between prevalent CVD and different thyroid function states with outcomes, hence, we did not exclude participants with prevalent CVD from data analysis. A total of 400 CVD events (358 CHD cases) during a median follow-up of 11.2 years (inter-quartile range: 1.96) occurred. During the follow-up, even in the age and sex adjusted model, no association was observed between different states of thyroid dysfunction and incidence of CVD/CHD. The multivariable hazard ratios (95% CI) of subclinical hypothyroidism, hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism for CVD events were 1.21 (0.77–1.88), 0.76 (0.33–1.69), 0.81 (0.46–1.41) and 1.48 (0.70–3.16), respectively. Both at baseline and during follow-up, no relation was observed between different states of thyroid function with prevalence and incidence of CVD/CHD.

  • The impact of iodine status on the recall rate of the screening program for congenital hypothyroidism: Findings from two national studies in Iran
    Ladan Mehran, Shahin Yarahmadi, Davood Khalili, Pantea Nazeri, Hossein Delshad, Zahra Abdollahi, Nasrin Azhang, and Fereidoun Azizi

    Nutrients, eISSN: 20726643, Published: November 2017 MDPI AG
    Back ground: Iodine deficiency is one of the important factors in increasing the recall rate in congenital hypothyroidism (CH) screening programs. The present study assessed whether the iodine status of the general population may predict the recall rate or vice versa. METHODS In the current national study, among 1,382,229 live births delivered between March 2010 and March 2011, 1,288,237 neonates were screened for detecting CH by TSH (thyroid stimulating hormone) measurement via heel prick sampling. Simultaneously, a total of 11,280 school-aged children, aged 7-8 years, were selected using random multi-cluster sampling for measurement of urinary iodine. RESULTS A negative correlation was found between median urinary iodine (MUI) and the recall rate (r = -0.33, p = 0.03). No correlation was found between MUIC (median urinary iodine concentration) and the incidence rate of CH. Linear regression analysis showed a 0.1% increase in the recall rate for a one unit decrease in MUIC (β = -0.11, 95% CI: -0.2, -0.1, p = 0.03). MUIC, at a cut-off point of 144.7 µg/L, was predictive for a recall rate < 3% (p = 0.05). CONCLUSION Frequencies of TSH ≥ 5 mU/L may be a more sensitive indicator for iodine status during pregnancy rather than in the general population. As higher recall rates reflect inadequate iodine nutrition, sufficient iodine supplementation is needed to reduce the recall rate in such communities.

  • Primordial and primary preventions of thyroid disease
    Fereidoun Azizi, Ladan Mehran, Farhad Hosseinpanah, Hossein Delshad, and Atieh Amouzegar

    International Journal of Endocrinology and Metabolism, ISSN: 1726913X, eISSN: 17269148, Published: 1 October 2017 Kowsar Medical Institute
    Background Primordial and primary preventions of thyroid diseases are concerned with avoiding the appearance of risk factors, delaying the progression to overt disease, and minimizing the impact of illness. Summary Using related key words, 446 articles related to primordial and primary, preventions of thyroid diseases published between 2001-2015 were evaluated, categorized and analyzed. Prevention and elimination of iodine deficiency are major steps that have been successfully achieved and maintained in many countries of the world in last 2 decades. Recent investigations related to the effect of cigarette smoking, alcohol consumption, and autoimmunity in the prevention of thyroid disorders have been reviewed. Conclusions The cornerstone for successful prevention of thyroid disease entails timely implementation of its primordial and primary preventions, which must be highly prioritized in related health strategies by health authorities.

  • Influence of topical iodine-containing antiseptics used during delivery on recall rate of congenital hypothyroidism screening program
    Majid Valizadeh, Farzaneh Moezzi, Zohreh Khavassi, Mohammad Movahedinia, Seideh Mazloomzadeh, and Ladan Mehran

    Journal of Pediatric Endocrinology and Metabolism, ISSN: 0334018X, eISSN: 21910251, Pages: 973-978, Published: 28 August 2017 Walter de Gruyter GmbH
    AbstractBackground:The proportion of newborns recalled during neonatal screening programs for congenital hypothyroidism (CH) varies substantially by country and may be higher in settings where povodine iodine (PVP-I) is used during delivery. We assessed this hypothesis by substituting PVP-I for chlorhexidine (CHL) and evaluated the reduction in the recall rate of the Irainian newborn screening program.Methods:This study investigated 2282 neonates of mothers admitted to a local hospital for delivery between December 2012 and October 2013. We measured thyorid stimulating hormone (TSH) levels in heel-prick blood specimens of infants, aged between 3 and 5 days, born to mothers who received PVP-I (phase I) and those who received CHL after withdrawal of PVP-I from obstetric procedures (phase II). Then we compared the median TSH levels and the recall rate based on a TSH level ≥5 mU/L.Results:Of 2282 cases, 1094 infants were born to mothers exposed to PVP-I during phase I (PVP-I group) and 1188 ones were born to mothers exposed to chlorhexidine in phase II (CHL group); 6.56% of the PVP-I group and 1.91% of the CHL group were recalled later during screening (p<0.001). The median TSH level was significantly higher in the PVP-I group compared to the CHL group (1.35 vs. 1.00, p<0.001).Conclusions:Replacement of iodine-containing antiseptics by iodine-free ones, during delivery resulted in a significant reduction in the recall rate of the Iranian screening program for CH.

  • Variations in Serum Free Thyroxine Concentration Within the Reference Range Predicts the Incidence of Metabolic Syndrome in Non-Obese Adults: A Cohort Study
    Ladan Mehran, Atieh Amouzegar, Mahmood Bakhtiyari, Mohammad Ali Mansournia, Parnian Kheirkhah Rahimabad, Maryam Tohidi, and Fereidoun Azizi

    Thyroid, ISSN: 10507256, eISSN: 15579077, Pages: 886-893, Published: July 2017 Mary Ann Liebert Inc
    BACKGROUND The association of changes in thyroid hormone values over time with the incidence of metabolic syndrome (MetS) has not yet been evaluated. For the first time, this study assessed the effect of thyroid hormone variations in the subclinical and euthyroid range on the incidence of MetS and its components over a 10-year follow-up in an adult population. METHODS Data were analyzed from the prospective population-based Tehran Thyroid Study. Of 5786 randomly selected subjects aged ≥20 years, after excluding subjects with MetS (n = 1403), those with serum thyrotropin (TSH) >10 or <0.1 mIU/L (n = 104), those taking thyroid drugs (n = 85) or corticosteroids (n = 97), those with a body mass index (BMI) <18.5 kg/m2, those with a glomerular filtration rate <30, and those with a history of cancer (12), data for 2393 subjects were analyzed. Body weight, waist circumference, and blood pressure were measured, and serum concentrations of lipids and lipoproteins, fasting blood glucose, insulin, free thyroxine (fT4), and TSH were assayed at baseline and during three follow-up studies at three-year intervals. MetS was determined using definition of the Joint Interim Statement, adjusted for the Iranian population. RESULTS An increase in fT4 values overtime was associated with lower odds of abdominal obesity (odds ratio [OR] = 0.49 [confidence interval (CI) 0.35-0.69]) and hypertriglyceridemia (OR = 0.57 [CI 0.41-0.78]), and with higher odds of hypertension (OR = 1.35 [CI 1.05-1.74]), adjusted for age, sex, smoking, BMI, and Homeostasis Model Assessment Index for Insulin Resistance. fT4 was associated with lower odds of MetS in the crude model, and after adjustment for age, sex, and smoking (OR = 0.59 [CI 0.39-0.9]). This association lost its significance after further adjusting for BMI. In a subgroup analysis of obese (i.e. BMI ≥30 kg/m2) and non-obese (i.e., BMI <30 kg/m2) subjects, fT4 was a significant predictor of MetS only in non-obese subjects after adjusting for age, sex, and smoking (β = 0.49 [CI 0.29-0.83], p = 0.007) and also after further adjustment for Homeostasis Model Assessment Index for Insulin Resistance (β = 0.57 [CI 0.34-0.96], p = 0.03). Serum TSH variations over time were not associated with any of the MetS components or with odds of MetS. CONCLUSION A decrease in serum fT4 values is associated with an increased risk for MetS, especially in non-obese adults.

  • Association between Thyroid Function and Body Mass Index: A 10-Year Follow-Up
    Hengameh Abdi, Elham Kazemian, Safoora Gharibzadeh, Atieh Amouzegar, Ladan Mehran, Maryam Tohidi, Zahra Rashvandi, and Fereidoun Azizi

    Annals of Nutrition and Metabolism, ISSN: 02506807, eISSN: 14219697, Pages: 338-345, Published: 1 July 2017 S. Karger AG
    Background/Aims: We aimed to evaluate the association between change in thyroid function tests within the euthyroid range and body mass index (BMI) in persons with normal weight at baseline. Methods: This study investigated 1,100 normal-weight euthyroid persons in a population-based cohort study, Tehran Thyroid Study. BMI was calculated and serum concentrations of thyrotropin (TSH) and free T4 (FT4) were assayed at baseline and after 10 years of follow-up. We evaluated the relationship between thyroid and obesity based on 2 definitions for outcome: (1) a binary outcome as BMI <25 or ≥25 kg/m2, and (2) a multinomial outcome as normal BMI, overweight, and obese. Results: A total of 569 women and 531 men, aged 36.3 ± 13.5 years, were included. Modified Poisson regression analysis for binary outcome, after adjustment for age, sex, smoking, and anti-thyroid peroxidase antibody status, revealed a negative association between delta serum FT4 and follow-up BMI (relative risk 0.55 [95% CI 0.37-0.80]) without any significant association between change in serum TSH and follow-up BMI. However, in multinomial logistic regression analysis, we found no relationship between delta serum FT4 or TSH and follow-up BMI categories, for either overweight or obese vs. normal-weight participants. Conclusions: In normal-weight euthyroid individuals, changes in serum concentrations of FT4, but not TSH, may contribute to change in body weight.

  • Natural Course of Euthyroidism and Clues for Early Diagnosis of Thyroid Dysfunction: Tehran Thyroid Study
    Atieh Amouzegar, Zahra Ghaemmaghami, Maani Beigy, Safoora Gharibzadeh, Ladan Mehran, Maryam Tohidi, and Fereidoun Azizi

    Thyroid, ISSN: 10507256, eISSN: 15579077, Pages: 616-625, Published: May 2017 Mary Ann Liebert Inc
    Objective: Considering the limited data available on the natural course of euthyroidism, this study was designed to evaluate the progression in time from euthyroidism to subclinical or overt hypo- or hyperthyroidism. Methods: This study was conducted within the framework of the Tehran Thyroid Cohort Study, in which 5783 individuals aged 40.4 ± 0.2 years were followed for six years. The overall loss to follow-up rate was 8.3%. After applying exclusion criteria, data of 4204 euthyroid subjects remained for analysis of a six-year natural course analysis. Thyroid function tests, clinical characteristics, and metabolic characteristics were assessed at baseline and every three years. Results: The annual incidence rates [confidence intervals (CI)] of subclinical and overt hypothyroidism were 7.62 [CI 7.39–7.85) and 2.0 [CI 1.94–2.06] per 1000 persons, respectively. For thyroid hyperfunction, the annual incidence rates of subclinical and overt hyperthyroidism were 0.92 [0.90–0.95) and 0.68 [0.66–0.70) per 1000 pe...

  • Thyroid Function and Metabolic Syndrome: A Population-Based Thyroid Study
    Ladan Mehran, Atieh Amouzegar, Parnian Rahimabad, Maryam Tohidi, Zhale Tahmasebinejad, and Fereidoun Azizi

    Hormone and Metabolic Research, ISSN: 00185043, eISSN: 14394286, Pages: 192-200, Published: 1 March 2017 Georg Thieme Verlag KG
    The impact of thyroid dysfunction in subclinical ranges on metabolic syndrome (MetS) is not well known. The aim of the present study is to evaluate the association of thyroid dysfunction with MetS and its components. In the cross-sectional population-based Tehran Thyroid Study, out of 5 786 randomly selected participants, aged≥20 years, subjects with thyroid nodules and cancer or any severe systemic disease, those who were pregnant and those using thyroid medication were excluded, leaving 5 422 subjects to be investigated. Body weight, waist circumference, and blood pressure were measured. Fasting blood glucose and concentrations of lipids and lipoproteins, free T4, and TSH were assayed. Mean age of the participants was 40.3±14.4 of whom 101 (2%) had overt hypothyroidism, 294 (5%) subclinical hypothyroidism, 82 (2%) overt hyperthyroidism, and 178 (3%) had subclinical hyperthyroidism; 1 704 (32%) had MetS. Clinically hypothyroid subjects had the highest prevalence of MetS (41.6%), abdominal obesity (45%), and hypertriglyceridemia (58%) compared to other groups (p<0.05). Significant odds ratio for prevalent MetS was observed only in clinically hypothyroid men [OR: 2.9, 95% CI: 1.04, 8.4, p=0.04]. In women, the association between overt hypothyroidism and MetS was marginally significant only in the crude model [OR: 0.068, 95% CI (0.97-2.42), p=0.06]. There was higher risk of Mets in subclinically hypothyroid subjects, aged>50. Overt and subclinical hyperthyroidism had significantly higher odds of hyperglycemia in men and women after full adjustment for age, smoking, and BMI. Overt hypothyroidism and subclinical hypothyroidism especially in the elderly could be associated with MetS. Hyperthyroidism may induce hyperglycemia.

  • The predictive value of metabolic syndrome for cardiovascular and all-cause mortality: Tehran Lipid and Glucose Study
    Atieh Amouzegar, Ladan Mehran, Mitra Hasheminia, Parnian Kheirkhah Rahimabad, and Fereidoun Azizi

    Diabetes/Metabolism Research and Reviews, ISSN: 15207552, eISSN: 15207560, Published: 1 January 2017 Wiley
    INTRODUCTION The association of total and cardiovascular disease (CVD) mortality with metabolic syndrome (Mets) is controversial. We estimated the predictive value of MetS and its components for total and CVD mortality. MATERIALS AND METHODS A total of 7932 subjects aged ≥ 30 years; participants of the Tehran Lipid and Glucose Study were enrolled and followed for 9.0 ± 2.3 years. MetS was defined according to three different definitions: World Health Organization (WHO), International Diabetes Federation (IDF) and Joint Interim Statement (JIS). RESULTS WHO-MetS remained a significant predictor of total and CVD mortality in men (HR 1.66, 95%CI 1.23-2.24, p < 0.001; 1.93 HR 1.93, 95%CI 1.26-2.94, p = 0.002) and women (HR 2.01, 95%CI 1.39-2.88, p < 0.001; HR 2.71, 95%CI 1.44-5.09, p = 0.002), respectively. IDF-MetS was associated with increased risk of total mortality only in women (HR 1.51, 95%CI 1.07-2.12, p = 0.01), but after controlling for diabetes, IDF and WHO-MetS lost their associations. The incidence of CVD mortality was highest in WHO group (13.4) compared with IDF (8.5), JIS (8.14) and control (5.5) groups. The incidence of total mortality for WHO (27.1) was highest compared with IDF (17.7), JIS (16.5) and control (12.9) groups. In men, hypertension, impaired fasting glucose (IFG) and abdominal obesity and in women, IFG (WHO criteria) and high triglycerides levels increased the risk of CVD mortality. In men, hypertension and IFG directly and high triglycerides inversely were associated with total mortality. In women, IFG and obesity increased the risk of all-cause mortality. CONCLUSION Diagnosis of MetS seems no more informative than its individual components in predicting mortality. Copyright © 2016 John Wiley & Sons, Ltd.

  • The prevalence, incidence and natural course of positive antithyroperoxidase antibodies in a population-based study: Tehran thyroid study
    Atieh Amouzegar, Safoora Gharibzadeh, Elham Kazemian, Ladan Mehran, Maryam Tohidi, and Fereidoun Azizi

    PLoS ONE, eISSN: 19326203, Published: January 2017 Public Library of Science (PLoS)
    OBJECTIVE Thyroid peroxidase antibody (TPOAb), the most common antibody frequently measured in population surveys is a protein expressed in the thyroid gland. We conducted the present study to analyze the prevalence and incidence of thyroid auto immunity and natural course of TPOAb in a population based study. MATERIAL AND METHODS This prospective study was conducted within the framework of the Tehran Thyroid Study (TTS) on 5783 (2376 men and 3407 women) individuals aged ≥ 20 years who had thyroid function tests at baseline and were followed up for median 9.1 year with TPOAb measurements at approximately every 3 years. RESULTS The mean age of total population at baseline was 40.04±14.32. At baseline, of the 5783 participants, 742 (12.8%) were TPOAb positive, with higher prevalence among women than in men (16.0 vs. 8.5%, p = 0.001). The prevalence of TPOAb positivity in the total population was 11.9, 14.9 and 13.6% in the young, middle age and elderly respectively. The total incidence rate (95%CI) of TPOAb positivity in the total population (5020) was 7.1 (6.36-7.98) per 1000 person-years of follow-up, with higher incidence of TPOAb positivity among young participants, i.e. 8.5 (7.5-9.7) per 1000 person-years. Sex specific incidence rate demonstrated that TPOAb positivity was higher in women, 9.3 (8.2-10.7) per 1000 person-years. The Cox's proportional hazard model analysis showed that the hazard ratio of developing TPOAb positivity was higher in women than men (P<0.0001) and tended to increase slightly with serum TSH levels (P<0.0001) but declined with increasing age (P<0.0001) in the total population. Our findings demonstrate that individuals, who became TPOAb positive in each phase, had significant elevation of TSH levels at the phase of seroconversion, compared to baseline values. CONCLUSION Gender, age and elevated serum TSH were found to be risk factors for developing TPOAb positivity. Furthermore, compared to baseline a significant elevation of TSH levels during seroconversion phase was observed in TPOAb positive individuals.

  • Worldwide recall rate in newborn screening programs for congenital hypothyroidism
    Ladan Mehran, Davood Khalili, Shahin Yarahmadi, Atieh Amouzegar, Mehdi Mojarrad, Nasrin Ajang, and Fereidoun Azizi

    International Journal of Endocrinology and Metabolism, ISSN: 1726913X, eISSN: 17269148, Published: 2017 Kowsar Medical Institute
    Context Neonatal mass screening program for congenital hypothyroidism provides the best tool for prevention of its devastating effects on mental development. Despite the overall success of the screening programs in detecting congenital hypothyroidism and eliminating its sequelae and new developments made in the program design, high recall rate and false positive results impose a great challenge worldwide. Lower recall rate and false positive results may properly organize project expenses by reducing the unnecessary repeated laboratory tests, increase physicians and parents' assurance and cooperation, as well as reduce the psychological effects in families. Evidence Acquisition In this review, we assessed the recall rate in different programs and its risk factors worldwide. Methods Publications reporting the results of the CH screening program from 1997 to 2016 focusing on the recall rate have been searched. Results Recall rates vary from 0.01% to 13.3% in different programs; this wide range may be due to different protocols of screening (use of T4 or TSH or both), different laboratory techniques, site of sample collection, recall cutoff, iodine status, human error, and even CH incidence as affected by social, cultural, and regional factors of the population. Conclusions It is suggested to implement suitable interventions to reduce the contributing factors by improving the quality of laboratory tests, selecting conservative cut off points, control iodine deficiency, use of iodine free antiseptic during delivery, and use of more specific markers or molecular tests. Applying an age dependent criteria for thyrotropin levels can be helpful in regions with a varied time of discharge after delivery or for preterm babies.

  • The Association between Blood Pressure and Normal Range Thyroid Function Tests in a Population Based Tehran Thyroid Study
    A. Amouzegar, M. Heidari, S. Gharibzadeh, L. Mehran, M. Tohidi, and F. Azizi

    Hormone and Metabolic Research, ISSN: 00185043, eISSN: 14394286, Pages: 151-156, Published: 1 March 2016 Georg Thieme Verlag KG
    Several studies have shown an association between overt hypothyroidism and diastolic hypertension. Association between subclinical hypothyroidism and hypertension is a matter of debate. The aim of this study was to examine the association of systolic and diastolic blood pressure, pulse pressure and mean arterial blood pressure with serum thyroid hormones levels in euthyroid subjects.Data from 4 756 individuals of the Tehran Thyroid study (TTS) without any previously known thyroid disease were analyzed. We divided participants based on TSH tertiles. Serum TSH and free T4 (FT4) concentration, systolic blood pressure (SBP), diastolic blood pressure (BPD) body mass index (BMI) were measured in all subjects.Among 5 786 individuals participated, 4 985 were euthyroid. After implementing exclusion criteria, 4 756 individuals remained of whom 2 122 (44.6%) were male and 2 634 (55.4%) were female. Multiple linear regression analysis revealed no association between TSH levels within reference ranges and blood pressure profile. No significant relationship was observed between TSH levels and systolic or diastolic blood pressure or the mean arterial pressure or pulse pressure in each tertile of TSH. There was a negative association between pulse pressure and TSH in the second tertile (r=- 0.066, p=0.009). Regression analysis showed that FT4 was significantly associated with systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure.No association was found between serum TSH and blood pressure profile in euthyroid subjects. Serum FT4 levels showed a positive association with blood pressure profiles.

  • Sex- and age-specific reference values and cutoff points for TPOAb: Tehran thyroid study
    Atieh Amouzegar, Mahmood Bakhtiyari, Mohammad Ali Mansournia, Ali Etemadi, Ladan Mehran, Maryam Tohidi, and Fereidoun Azizi

    Thyroid, ISSN: 10507256, eISSN: 15579077, Pages: 458-465, Published: 1 March 2016 Mary Ann Liebert Inc
    BACKGROUND Current guidelines used for establishing reference intervals for thyroid peroxidase antibodies (TPOAb), recommended by the National Academy of Clinical Biochemistry, have been a matter of controversy. The present study sought to determine TPOAb reference intervals for different age and sex groups, as well as the TPOAb cutoff points for subclinical and overt hypothyroidism in an iodine-sufficient population. METHODS This cross-sectional study was conducted within the framework of the prospective Tehran Thyroid Study (TTS), in which 4174 healthy euthyroid individuals were followed for 10 years. Thyroid function tests and TPOAb were assessed. RESULTS The mean age ± standard deviation of participants was 39.3 ± 15.2 years. Estimated reference intervals for TPOAb corresponding to the 2.5th and 97.5th percentiles were 1.5-32.8 and 2.1-35 IU/mL in males and females, respectively. There were no significant variations in the different age groups in either sex. The optimal cutoff points for TPOAb were 18.38 and 14.77 IU/mL for predicting clinical and subclinical hypothyroidism, respectively. CONCLUSIONS This study establishes the reference intervals and the optimal cutoff points for TPOAb in an iodine-sufficient population.

  • Prevalent practices of thyroid diseases during pregnancy among endocrinologists, internists and general practitioners
    Fereidoun Azizi, Ladan Mehran, Atieh Amouzegar, Shahram Alamdari, Imam Subetki, Navid Saadat, Siamak Moini, and Farzaneh Sarvghadi

    International Journal of Endocrinology and Metabolism, ISSN: 1726913X, eISSN: 17269148, Published: 2016 Kowsar Medical Institute
    BACKGROUND Maternal thyroid disease in pregnancy is associated with adverse impact on both mother and fetus. Both the American thyroid association and the endocrine society have recently published guidelines for the management of thyroid disease in pregnancy. OBJECTIVES The objective of this survey was to assess and compare the current practices of various East-Asian physicians in the screening and management of thyroid disease in pregnancy. MATERIALS AND METHODS Completed survey questionnaires were collected from 112 physicians of six East-Asian countries. The survey was based on clinical case scenarios, asking questions about the clinical practices related to diagnosis and management of thyroid disease during pregnancy. Reponses from 76 endocrinologists and 33 internists and general practitioners (generalists) were analyzed. RESULTS There were minor differences in treatment preferences for Graves' disease in pregnancy and tests to monitor antithyroid drugs between endocrinologists and generalists; the major difference being targeted free thyroxin, and also thyroxin, depicted in the upper end of normal range, by the majority of endocrinologist and within the normal range, by generalists. Compared to generalists, endocrinologists perform more targeted screening and are more familiar with its risk factors. Predominantly, endocrinologists increase levothyroxine dose in hypothyroid women, upon confirmation of pregnancy and also indicate full dose in a pregnant woman, diagnosed with overt hypothyroidism, and treat thyroid peroxidase antibody positive or negative pregnant women with thyroid stimulating hormone (2.5 - 5 mU/L), as compared to generalists. CONCLUSIONS There is wide variation in the clinical practices of screening and management of thyroid disorders during pregnancy in East-Asia, with many clinicians, in particular general practitioners, not adhering to clinical practice guidelines, unfortunately.

  • Maternal Thyroid Function and Autoimmunity in 3 Trimesters of Pregnancy and their Offspring's Thyroid Function
    P. Sarkhail, L. Mehran, S. Askari, Z. Tahmasebinejad, M. Tohidi, and F. Azizi

    Hormone and Metabolic Research, ISSN: 00185043, eISSN: 14394286, Pages: 20-26, Published: 13 November 2015 Georg Thieme Verlag KG
    This study was performed to evaluate maternal thyroid dysfunction and autoimmunity during pregnancy and its correlation with thyroid function of offspring. In this cohort study, Serum TT4, TT3, T3U, TSH, TPOAb, and TgAb were measured. Serum samples of 120 pregnant women were collected during 3 trimesters as well as in 57 cord bloods, 69 neonates, 34, 37, and 36 infants aged 2, 4, and 6 months. Repeated measure and Pearson correlation test were used to compare thyroid hormone values and to assess the correlations, respectively. Main outcomes were correlations between thyroid hormones and antibodies in mothers and offspring. An increasing trend for TT3 (p for trend < 000.1) and TSH (p for trend 0.01) was found over the course of gestation. Among 120 mothers, 10 (8%) had subclinical hyperthyroidism and 18 mothers (15%) showed subclinical hypothyroidism. We found one hypothyroid (0.8%) and 3 hyperthyroid (2.5%) mothers during pregnancy. Correlations among maternal thyroid hormones were found but not with auto-antibodies. A positive correlation between maternal thyroid auto-antibodies in all trimesters with cord blood and neonates was found. Cord blood TSH had a good correlation with maternal TSH, but only in the first trimester (r=0.29, p<0.05). A positive correlation between neonatal TSH and maternal TT4 was found only in the third trimester (r=0.25, p<0.05). Subclinical hypothyroidism was the most common thyroid dysfunction in the pregnant women studied. The association between maternal auto-antibodies and thyroid hormones of offspring was observed mostly in the neonatal period and became weaker after one month of age.

  • Association between thyroid hormones, thyroid antibodies and insulinresistance in euthyroid individuals: A population-based cohort
    A. Amouzegar, E. Kazemian, S. Gharibzadeh, L. Mehran, M. Tohidi, and F. Azizi

    Diabetes and Metabolism, ISSN: 12623636, eISSN: 18781780, Pages: 480-488, Published: December 02, 2014 Elsevier BV
    AIM The association between insulin resistance and thyroid function in euthyroid subjects has not yet been clarified. This study aimed to investigate the association between thyroid function within the normal reference range and insulin resistance in participants of the Tehran Thyroid Study (TTS). METHODS This cross-sectional study was conducted within the framework of the TTS. Of 5786 subjects aged ≥ 20 years, 2758 euthyroid subjects free of thyroid disorders, diabetes, chronic kidney disease and cardiovascular disease, and not taking steroids and lipid-lowering agents, were included. Serum concentrations of free thyroxine (FT4) and TSH were measured. The homoeostasis model assessment index for insulin resistance (HOMA-IR) was used to evaluate IR. RESULTS On linear regression analysis, a negative association was found between serum FT4 levels and HOMA-IR in the model with age, smoking and physical activity (B = -0.09, P < 0.001) and in the WC-adjusted model with age, smoking and physical activity for men (B = -0.06, P < 0.01). In addition, there was a positive association between serum TSH levels and HOMA-IR in both models [with age, smoking and physical activity (B = 0.07, P = 0.006), and age, smoking, physical activity and adjusted for WC (B = 0.05, P = 0.01)] that was not more significant on logistic regression analysis. In women, neither serum FT4 nor TSH levels were associated with HOMA-IR; the prevalence of IR decreased from 27.2 to 19.1 with increasing tertiles of FT4 only in men (P = 0.01). No significant differences were observed in HOMA-IR and its components between thyroid peroxidase antibody (TPOAb)-negative and -positive groups. Also, it was found that metabolically healthy but obese (MHO) subjects had higher levels of TSH than individuals who were MONW (metabolically obese but normal weight; P < 0.01). CONCLUSION Low FT4 was independently associated with IR in healthy euthyroid Iranian men.

  • Comparison of two guidelines on management of thyroid nodules and thyroid cancer during pregnancy
    Archives of Iranian Medicine, ISSN: 10292977, eISSN: 17353947, Pages: 670-673, Published: 1 October 2014

  • Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects
    Ladan Mehran, Atieh Amouzegar, Maryam Tohidi, Maryam Moayedi, and Fereidoun Azizi

    Thyroid, ISSN: 10507256, eISSN: 15579077, Pages: 1566-1574, Published: 2014 Mary Ann Liebert Inc
    CONTEXT The association between thyroid hormones within the euthyroid range and metabolic syndrome is not clear. AIM This study evaluated the relationship between thyroid hormones and metabolic syndrome and its components in euthyroid subjects. DESIGN AND SETTING This is a cross-sectional population based study conducted within the framework of the cohort of the Tehran Thyroid Study. PARTICIPANTS Out of 5786 subjects aged ≥ 20 years, 3755 euthyroid subjects without a history of thyroid disorders, diabetes, or use of steroids or lipid-lowering agents were investigated. OUTCOME MEASURES Body weight, waist circumference (WC), and blood pressure (BP) were measured. Serum concentrations of lipids and lipoproteins, fasting blood glucose (FBG), insulin, free T4 (FT4), and thyrotropin (TSH) were assayed. Metabolic syndrome was determined by definition of the Joint Interim Statement adjusted for the Iranian population. RESULTS After adjustment for age, sex, and smoking, serum FT4 was significantly associated with high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), WC, systolic BP, and diastolic BP; the associations that remained significant after further adjustment for body mass index (BMI) and the homeostasis model assessment index for insulin resistance (HOMA-IR) except for HDL-C. Serum TSH was associated only with TGs after adjustments for age, sex, smoking, and BMI, an association that disappeared after further adjustment for HOMA-IR. Serum FT4 was negatively associated (β=-0.02, 95% confidence interval [CI: -0.03, -0.01]) and TSH was positively associated (β = 0.03 [CI: 0.01, 0.04) with insulin resistance. The prevalence of metabolic syndrome decreased from 30.1% in the lowest FT4 tertile to 22.4% in the highest FT4 tertile (p<0.001). The prevalence of other metabolic syndrome components decreased significantly from higher to lower FT4 tertiles. Higher FT4 values were associated with lower odds of metabolic syndrome (OR = 0.96 [95% CI: 0.92, 0.99]; p=0.01). CONCLUSION In euthyroid subjects, FT4, rather than TSH, is associated with risk of metabolic syndrome and its components.

  • Prevention of iodine-deficiency induced goiter and brain damage in the Islamic Republic of Iran
    Iranian Journal of Endocrinology and Metabolism, ISSN: 16834844, eISSN: 16835476, Pages: 411-429, Published: 2014

  • Prevalence of hypothyroidism in patients with dyslipidemia: Tehran Thyroid Study (TTS)
    M. Khazan, A. Amouzegar, S. Gharibzadeh, L. Mehran, M. Tohidi, and F. Azizi

    Hormone and Metabolic Research, ISSN: 00185043, eISSN: 14394286, Pages: 980-984, Published: December 2014 Georg Thieme Verlag KG
    Hypothyroidism is a relatively common endocrine disorder usually accompanied with changes in serum lipid profiles. The purpose of this study was to assess the association between dyslipidemia and hypothyroidism in a population-based study. In this cross-sectional study, 2,315 dyslipidemic patients, aged 20-90 years (mean age: 38.1 ± 13.2 years), were selected from among 5,760 participants of Tehran Thyroid Study and divided into 3 groups, the subclinical hypothyroid, overt hypothyroid, and euthyroid subjects, based on national reference ranges. Serum lipid profiles, free thyroxine (FT4), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured in all subjects. In subjects with dyslipidemia and nondyslipidemia, the prevalence of subclinical was 7% and 4.1%, respectively, and for clinical hypothyroidism 3% and 1.2%, respectively. In dyslipidemic subjects, the mean low density lipoprotein-cholesterol (LDL-C) levels differed significantly (p = 0.03) among the overt hypothyroid (144.3 ± 36.1), subclinical hypothyroid (129.3 ± 39.2), and euthyroid (132.7 ± 39.0) groups. In the overt hypothyroid group, mean total cholesterol level was higher than in the normal group, but not significant. There were no differences in median triglycerides (TG) and mean high density lipoprotein-cholesterol (HDL-C) levels among the 3 groups mentioned. After adjusting for age and sex, hypothyroidism was not related to elevated serum lipid profiles in patient with dyslipidemia. In conclusion, there is significant difference in the prevalence of subclinical and clinical hypothyroidism between nondyslipidemic and dyslipidemic subjects; after adjustment for age and sex the presence of dyslipidemia did not predict the presence of hypothyroidism.

  • Comparison of the American thyroid association with the endocrine society practice guidelines for the screening and treatment of hypothyroidism during pregnancy
    Atieh Amouzegar, Ladan Mehran, Farzaneh Sarvghadi, Hossein Delshad, Fereidoun Azizi,, and John Lazarus

    Hormones, ISSN: 11093099, Pages: 307-313, Published: June 2014 Springer Science and Business Media LLC
    Using recent Endosociety guidelines for definition of subclinical hypothyroidism, i.e. a serum TSH >2.5 mIU/L during the first and TSH >3 mIU/L during second and third trimesters, will also increase the prevalence of subclinical hypothyroidism. In a study, Shields et al reported the prevalence of subclinical hypothyroidism in pregnancy (TSH >3 mIU/L) to be 12.4% in pregnant women during routine antenatal care.

  • Local versus international recommended TSH references in the assessment of thyroid function during pregnancy
    A. Amouzegar, E. Ainy, M. Khazan, L. Mehran, M. Hedayati, and F. Azizi

    Hormone and Metabolic Research, ISSN: 00185043, eISSN: 14394286, Pages: 206-210, Published: March 2014 Georg Thieme Verlag KG
    The aim of this study was to compare the prevalence of subclinical and overt hypothyroidism based on local population-specific reference intervals versus arbitrary cutoffs that are not specific for the population studied or the assay used, during pregnancy in an area of iodine sufficiency. We tested a total of 203 pregnant women in the first trimester of pregnancy, and followed their status in the second and third trimesters. Serum samples from women were assayed for levels of total T4 and T3, FT4I, TSH, TPOAb, and TgAb. Of the 203 women based on our national trimester specific reference ranges of serum TSH and FT4I, 153, 157, and 157 were euthyroid in 3 consecutive trimesters of pregnancy. Accordingly, a total of 23, 12, and 13 had subclinical hypothyroidism in the first, second, and third trimester, respectively. Overt hypothyroidism was detected in 4, 5, and 1 women in the first, second, and third trimesters of pregnancy, respectively. The prevalence of subclinical hypothyroidism was 49, 31, and 34 in each of the trimesters respectively, when TSH>2.5 mIU/l was considered for definition of hypothyroidism in the first trimester, and over 3 mIU/l in the second and third trimesters. Our results showed that using arbitrary cutoff values for TSH instead of population-specific reference intervals may inappropriately increase the rate of subclinical hypothyroidism.

  • Screening and management of hypothyroidism in pregnancy: Results of an Asian survey
    Fereidoun Azizi, Atieh Amouzegar, Ladan Mehran, Shahram Alamdari, Imam Subekti, Bijay Vaidya, Kris Poppe, Teofilo San Luis Jr, and Takashi Akamizu

    Endocrine Journal, ISSN: 09188959, eISSN: 13484540, Pages: 697-704, Published: 2014 Japan Endocrine Society
    Maternal hypothyroidism in pregnancy is associated with several adverse outcomes. The American Thyroid Association and the Endocrine Society Guidelines for the management of thyroid diseases in pregnancy were published in 2011 and 2012, respectively; however, impact of the guidelines in routine clinical practice is unknown. We therefore carried out a survey to study current practices in the screening and management of hypothyroidism in pregnancy. We collected completed questionnaire survey based on clinical case scenarios from 321 members of the Asia-Oceania Thyrpid Association (AOTA). Responses from 310 clinician members (from 21 Asian countries) were analyzed. For a woman with hypothyroidism planning pregnancy, 54% favored testing thyroid function before adjusting the dose, whilst 32% recommended increasing the dose of L-thyroxine (L-T₄) as soon as pregnancy is confirmed. For a pregnant woman with newly diagnosed overt hypothyroidism, most responders initiated a full dose of L-T₄. One half of responders used serum TSH and free T₄ to monitor the dose of L-T₄. Although the target of thyroid function tests that responders aimed to achieve with L-T₄ was inconsistent, but a majority aim to keep TSH within recommended trimester specific range. Twenty-one % responders or their institutions screened all pregnant women for thyroid dysfunction, 66% performed targeted screening of only the high-risk group, whilst 13% did not carry out systemic screening. Majority of responders practices within recommendations of major professional societies; however, there is wide variation in the clinical practice in the treatment and screening of hypothyroidism during pregnancy in Asia.

  • Management of hyperthyroidism during pregnancy in Asia
    Fereidoun Azizi, Atieh Amouzegar, Ladan Mehran, Shahram Alamdari, Imam Subekti, Bijay Vaidya, Kris Poppe, Farzaneh Sarvghadi, Teofilo San Luis Jr, and Takashi Akamizu

    Endocrine Journal, ISSN: 09188959, eISSN: 13484540, Pages: 751-758, Published: 2014 Japan Endocrine Society
    Maternal hyperthyroidism in pregnancy is associated with adverse impacts on both mother and fetus. Recently, the American Thyroid Association and the Endocrine Society have published guidelines for the management of thyroid diseases in pregnancy. We aimed to disclose the impact of these guidelines in current practices of Asian members of the Asia-Oceania Thyroid Association (AOTA) regarding the management of hyperthyroidism in pregnancy. Completed questionnaire survey, based on clinical case scenarios, was collected from 321 Asian physician members of AOTA from 21 Asian countries in 2013. For a woman with Graves' disease planning pregnancy, 92% of clinicians favored antithyroid treatment, 52% with propylthiouracil (PTU) while 40% preferred methimazole (MMI). For a pregnant woman with newly diagnosed overt hyperthyroidism, nearly all responders initiated PTU treatment. To monitor dosage of antithyroid drugs, approximately 73% of responders used TSH and free T4 (FT4) levels without free T3 (FT3) (53%) or with FT3 (20%). Majority of responders targeted achieving low serum TSH with FT4 (or total T4) in the upper end of the normal range. For management of gestational thyrotoxicosis, 40% chose to follow up and 52% treated patients with PTU. Although timing of TSH receptor antibodies measurement in pregnant hyperthyroid patients was variable, 53% of responders would check it at least once during pregnancy. Nearly 80% of responders do not treat subclinical hyperthyroidism in pregnancy. Therefore, despite wide variations in the management of hyperthyroidism during pregnancy in Asia, majority of Asian physicians practice within the recommendations of major professional societies.

  • Reference limit of thyrotropin (TSH) and free thyroxine (FT4) in thyroperoxidase positive and negative subjects: A population based study
    Atieh Amouzegar, Hossein Delshad, Ladan Mehran, Maryam Tohidi, F. Khafaji and Freidoon Azizi

    Journal of Endocrinological Investigation, ISSN: 03914097, eISSN: 17208386, Pages: 950-954, Published: December 2013
    Background: Current reference values for thyroid function tests are based on data from different ethnicities and geographical areas. The aim of the present study was to determine reference intervals for thyrotropin (TSH) and free T4 (FT4), based on the criteria of the National Academy of Clinical Biochemistry (NACB) in an Iranian population. Material and methods: This study was conducted within the framework of Tehran Thyroid Study (TTS), an ongoing prospective cohort of 5704 randomly selected individuals, age ≥20 yr. A total of 2199 individuals (43.3% male, 56.7% female), based on NACB criteria were included in this study. Reference limit analysis was performed for the negative thyroid peroxidase antibody (TPOAb) group. Results: After applying all exclusion criteria except TPOAb positivity (10.5%), data of 2459 participants remained for analysis. Of these, 953 (43.3%) were males and 1246 (56.7%) were females; the mean±SD age was 43.53±14.16 yr. The mean±SD and median+IQR for TSH were 1.77 mU/l ±1.24 and 1.46 (0.93–2.23) mU/l, respectively. The 2.5th and 97.5th percentiles TSH were 0.32 mU/l and 5.06 mU/l respectively. The mean±SD and median (IQR) for FT4 for all negative TPOAb subjects were 1.19±0.16 and 1.18 (1.08–1.31) ng/dl respectively. Conclusion: Reference ranges for thyroid function tests need to be derived from national databases. This study determined age and sex specific TSH and FT4 reference ranges in a Tehranian population, which could eventually enable clinicians to classify patients more appropriately.

  • Iodine nutrition status and knowledge, attitude, and behavior in Tehranian women following 2 decades without public education
    Parvin Mirmiran, Pantea Nazeri, Parisa Amiri, Ladan Mehran, Nezhat Shakeri, and Fereidoun Azizi

    Journal of Nutrition Education and Behavior, ISSN: 14994046, Pages: 412-419, Published: September 2013 Elsevier BV
    OBJECTIVE To evaluate the association of iodine nutrition status and knowledge, attitude, and behavior in Tehranian women after 2 decades without updating public education. DESIGN Cross-sectional study. SETTING Eight health care centers from 4 district areas of Tehran. PARTICIPANTS A total of 383 women aged ≥ 19 years, randomly selected. MAIN OUTCOME MEASURES Iodine concentration of 24-hour urine samples, iodine content of household salts, and knowledge, attitude, and practice scores regarding iodine nutrition and iodized salt. ANALYSIS Multiple logistic regression was used to identify the association of knowledge, attitude, and practice scores with urinary iodine concentration (UIC) < 100 μg/L. RESULTS The percentages of Tehranian women with high knowledge, attitude, and practice scores were 26%, 26%, and 14%, respectively. Practice score was significantly different between females with UIC < 100 and > 100 μg/L (P = .001). Risk of UIC < 100 μg/L in women of childbearing age (19-45 years) after adjustment of education level, region of residence, and iodine content of salt was significantly associated with intermediate practice score (odds ratio = 2.6; 95% confidence interval, 1.3-13.2). CONCLUSIONS AND IMPLICATIONS Marginally suboptimal iodine status in women of childbearing age can be attributed to inappropriate practices, but not to knowledge and attitude.

  • Trimester-specific reference ranges for thyroid hormones in iranian pregnant women
    Ladan Mehran, Atieh Amouzegar, Hossein Delshad, Sahar Askari, Mehdi Hedayati, Golshan Amirshekari, and Fereidoun Azizi

    Journal of Thyroid Research, ISSN: 20908067, eISSN: 20420072, Volume: 2013, Published: 2013 Hindawi Limited
    Background. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester-specific reference intervals for a specific population. There is no normative data documented for thyroid hormones on healthy pregnant women in Iran. The present survey was conducted to determine trimester-specific reference ranges for serum TSH, thyroxine (TT4), and triiodothyronine (TT3).Methods. The serum of 215 cases was analyzed for measurement of thyroid function tests by immunoassay method of which 152 iodine-sufficient pregnant women without thyroid autoantibodies and history of thyroid disorder or goiter were selected for final analysis. Reference intervals were defined as 5th and 95th percentiles.Results. Reference intervals in the first, second, and third trimesters were as follows: TSH (0.2–3.9, 0.5–4.1, and 0.6–4.1 mIU/l), TT4 (8.2–18.5, 10.1–20.6, and 9–19.4 μg/dl), and TT3 (137.8–278.3, 154.8–327.6, and 137–323.6 ng/dl), respectively. No correlation was found between TSH and TT4 or TT3. Significant correlation was found between TT4 and TT3 in all trimesters (r=0.35,P<0.001).Conclusion. The reference intervals of thyroid function tests in pregnant women differ among trimesters. Applying trimester-specific reference ranges of thyroid hormones is warranted in order to avoid misclassification of thyroid dysfunction during pregnancy.

  • Natural course of thyroid disease profile in a population in nutrition transition: Tehran thyroid study
    Archives of Iranian Medicine, ISSN: 10292977, eISSN: 17353947, Pages: 418-423, Published: July 2013

  • Erratum: Establishment of the trimesterspecific reference range for free thyroxine index (Thyroid (2012) 23 (354-359))
    Azizi, Mehran, Amouzegar, Delshad, Tohidi, Askari and Hedayati

    Thyroid, ISSN: 10507256, eISSN: 15579077, Pages: 915, Published: 1 July 2013 Mary Ann Liebert Inc

  • Management of hyperthyroidism in pregnancy: Comparison of recommendations of american thyroid association and endocrine society
    Shahram Alamdari, Fereidoun Azizi, Hossein Delshad, Farzaneh Sarvghadi, Atieh Amouzegar, and Ladan Mehran

    Journal of Thyroid Research, ISSN: 20908067, eISSN: 20420072, Volume: 2013, Published: 2013 Hindawi Limited
    Appropriate diagnosis and treatment of hyperthyroidism during pregnancy are of outmost importance, because hyperthyroidism has major adverse impact on both mother and fetus. Since data on the management of thyroid dysfunction during pregnancy is rapidly evolving, two guidelines have been developed by the American Thyroid Association and the Endocrine society in the last 2 years. We compare here the recommendations of these two guidelines regarding management of hyperthyroidism during pregnancy. The comparison reveals no disagreement or controversy on the various aspects of diagnosis and treatment of hyperthyroidism during pregnancy between the two guidelines. Propylthiouracil has been considered as the first-line drug for treatment of hyperthyroidism in the first trimester of pregnancy. In the second trimester, consideration should be given to switching to methimazole for the rest of pregnancy. Methimazole is also the drug of choice in lactating hyperthyroid women.

  • Management of thyroid peroxidase antibody euthyroid women in pregnancy: Comparison of the american thyroid association and the endocrine society guidelines
    L. Mehran, M. Tohidi, F. Sarvghadi, H. Delshad, A. Amouzegar, O. P. Soldin, and F. Azizi

    Journal of Thyroid Research, ISSN: 20908067, eISSN: 20420072, Volume: 2013, Published: 2013 Hindawi Limited
    The presence of thyroid autoantibodies is relatively high in women of childbearing age. There is evidence that positive thyroperoxidase antibody even in euthyroid women may increase the risk of spontaneous and recurrent pregnancy loss and preterm delivery. However, the evidence is not enough to justify recommendation on the screening of pregnant women for thyroid autoantibodies or LT4 supplementation for reducing maternal or fetal complications. In this paper we reviewed the related evidence and compared the new guidelines of the American Thyroid Association and Endocrine Society with respect to the screening and management of positive thyroperoxidase antibody in euthyroid pregnant women. As there was no major contradiction or disagreement between the two guidelines, either one of two guidelines may be used by clinicians for the appropriate management of thyroid autoimmunity during pregnancy.

  • Does a text messaging intervention improve knowledge, attitudes and practice regarding iodine deficiency and iodized salt consumption?
    Ladan Mehran, Pantea Nazeri, Hossein Delshad, Parvin Mirmiran, Yadollah Mehrabi, and Fereidoun Azizi

    Public Health Nutrition, ISSN: 13689800, eISSN: 14752727, Pages: 2320-2325, Published: December 2012 Cambridge University Press (CUP)
    AbstractObjectiveTo determine the effectiveness of implementation of a prevention programme via mobile phone text messaging in enhancing knowledge, attitudes and practice concerning iodine deficiency and iodized salt consumption.DesignIn a randomized controlled trial, participants were subjected to a brief tele-educational support regarding iodine deficiency and the importance of iodized salt consumption. The intervention group received daily text messages via mobile phone for 6 weeks. Knowledge, attitude and practice scores, urinary iodine concentration and salt iodine content were assessed at baseline and 8 weeks after the intervention.SettingParticipants were recruited from health-care centres in Tehran, the capital city of Iran.SubjectsFor the present study 205 females aged ≥18 years were randomly assigned to the intervention (n 95) and control (n 110) groups.ResultsA significant difference was found in median knowledge scores between the intervention and control groups at follow-up (P = 0·004). There was also a significant difference in median attitude scores between the intervention and control groups (P = 0·02). The intervention group did not differ significantly in median practice score, urinary iodine concentration and salt iodine content from the control group.ConclusionsText messaging interventions are effective in improving individuals’ knowledge and attitudes regarding preventive health-care topics.

  • Association between serum TSH concentration and body mass index in euthyroid subjects: The role of smoking
    Archives of Iranian Medicine, ISSN: 10292977, eISSN: 17353947, Pages: 400-403, Published: July 2012

  • The incidence of thyroid function abnormalities and natural course of subclinical thyroid disorders, Tehran, I.R. Iran
    Hossein Delshad, Ladan Mehran, Mohammad-Reza Tohidi, Mahdi Assadi and Freidoon Azizi

    Journal of Endocrinological Investigation, ISSN: 03914097, eISSN: 17208386, Pages: 516-521, Published: May 2012
    Background: Despite the high prevalence of thyroid dysfunction, the epidemiology and natural course of these disorders have not been identified yet. Aim: The present survey was conducted to determine the incidence of thyroid dysfunction and natural course of subclinical thyroid disorders in an urban community of Tehran, I.R. Iran. Subjects and methods: Serum TSH and thyroperoxidase antibody (TPOAb) were measured at baseline and after 6.7 yr from a sample of 1999 randomly selected subjects aged ≥20 yr, participants of the Tehran Lipid and Glucose Study (TLGS). Median TSH value and 2.5, 5, 95, and 97.5 TSH percentiles were determined at baseline using data obtained from 808 negative TPOAb subjects with no history of any thyroid disease or surgery, goiter, nodule, taking thyroid hormone preparations or anti-thyroid drugs. In those with abnormal TSH level, total T4 and T3 uptake were measured and free T4 index was calculated. Results: Normal TSH reference range was 0.4–5.8 µU/ml according to the 2.5 and 97.5 TSH percentiles. The incidence rates of thyroid function abnormalities in 1000 subjects per year were as follows: clinical hypothyroidism: 0.28 in women and 0.21 in men; subclinical hypothyroidism: 11.59 in women and 4.69 in men; clinical hyperthyroidism: 1.4 in women and 0.21 in men; and subclinical hyperthyroidism: 5.72 in women and 3.62 in men. A significant increase was found in the frequency of positive TPOAb in women from 15.9 to 17.7% (p=0.006). Of 8 women with subclinical hypothyroidism at baseline, 5 remained unchanged, 1 became normal, and 1 developed clinical hypothyroidism at follow-up. Two women with subclinical hyperthyroidism normalized at follow-up. Of 2 men with subclinical hypothyroidism at baseline, 1 remained unchanged, whereas the other progressed to clinical hypothyroidism. Conclusion: After a 6.7 yr follow-up significant increase in the incidence of subclinical thyroid disorders was observed in both men and women, as compared to overt thyroid dysfunction. Increase in the prevalence of TPOAb positivity was observed only in women.

  • Eighteen years of continuously sustained elimination of iodine deficiency in the Islamic Republic of Iran: The vitality of periodic monitoring
    Hossien Delshad, Atieh Amouzegar, Parvin Mirmiran, Ladan Mehran, and Fereidoun Azizi

    Thyroid, ISSN: 10507256, eISSN: 15579077, Pages: 415-421, Published: 1 April 2012 Mary Ann Liebert Inc
    BACKGROUND Two decades ago the Islamic Republic of Iran was among countries most severely affected by iodine deficiency. Iran has since achieved great success in the control and elimination of iodine deficiency disorders (IDDs) following the national salt iodization program, initiated in 1989. The aim of the study was to evaluate the effectiveness of sustained consumption of iodized salt by Iranian households and the current status of iodine nutrition in all 30 provinces of Iran. METHODS Goiters-measured by palpation-and urinary iodine concentration of children were assessed. In this descriptive cross-sectional study, 36,000 schoolchildren (18,000 girls and 18,000 boys), aged 8-10 years, were randomly selected, from October 2007 to February 2008, from 30 provinces of the country. Goiter prevalence and urinary iodine excretion in schoolchildren and the iodine content of salt at household, factory, and distribution site levels were measured. RESULTS The goiter rate in the country was 6.5% (6% grade 1 and 0.5% grade 2), and the weighted goiter rate was 5.7%. The total goiter rate in Hamedan, Zanjan, Kermanshah, Mazandaran, and Gilan provinces was over 10%. The median urinary iodine was 140 μg/L. Urinary iodine levels of 20-50, 50-99, and ≥100 μg/L were noted in 15.3%, 19.8%, and 64.9% of the samples, respectively. In four provinces, the median urinary iodine was lower than 100 μg/L. The mean (±SD) and median salt iodine values were 23.2 (±13.8) and 34.7 ppm, respectively, at the production level, and 32.4 (±14.7) and 32.3 ppm, respectively, at the distribution level. Ninety-eight percent of households consumed iodized salt, 58% of households had appropriate salt storage, and 27% of the household salts contained <20 ppm. CONCLUSIONS Iran has achieved much in the development of universal salt iodization strategy and elimination of IDDs and currently meets all criteria for sustainable elimination of iodine deficiency. However, the lack of adequate iodine nutrition in some provinces necessitates special attention and proper monitoring.

  • The Association of cigarette smoking with serum TSH concentration and thyroperoxidase antibody
    L. Mehran, A. Amouzgar, H. Delshad, and F. Azizi

    Experimental and Clinical Endocrinology and Diabetes, ISSN: 09477349, eISSN: 14393646, Volume: 120, Pages: 80-83, Published: 2012 Georg Thieme Verlag KG
    AbstractAlthough several studies have found an association between tobacco smoking and thyroid disorders such as Graves’ disease, Graves’ ophtalmopathy, goiter and thyroid multi nodularity, the effect of smoking on thyroid function is controversial.The aim of this study was to evaluate the association between smoking and serum TSH concentration and the presence of thyroperoxidase antibody (TPO Ab) in Tehranian adults.In this cross sectional community based survey, 1 581 randomly selected subjects with no history of thyroid disorders were studied within the framework of Tehran Lipid and Glucose Study. Serum TSH and TPOAb were measured in a fasting serum sample. Weight and height were measured and BMI was calculated. Smokers were classified into ever and never smokers based on the declaration of participants.Mean Ln TSH values in the ever smoker (0.36±0.82) was significantly lower than the never smoker (0.6±0.82) group (p<0.001) even after adjustment for age and BMI. The odds ratio for hypothyroidism (TSH>5.8) was 0.4 in the ever smoker group compared to the never one (odds ratio 0.4, 95% CI=0.2–0.8). The frequency of positive TPOAb in never smokers was significantly higher than ever smokers (%13.5 vs. % 6.7, p<0.001).The results suggest that smoking is associated with decreased serum TSH concentrations, lower risk of hypothyroidism and possibly with a lower frequency of thyroid auto immunity.

  • Appropriate iodine nutrition in Iran: 20 years of success
    Acta Medica Iranica, ISSN: 00446025, eISSN: 17359694, Pages: 361-366, Published: 2010

  • Continuous adequate iodine supplementation in fars province: The 2007 goiter and urinary iodine excretion survey in schoolchildren
    Iranian Journal of Medical Sciences, ISSN: 02530716, eISSN: 17353688, Pages: 16-20, Published: March 2010

  • Sustainability of a well-monitored salt iodization program in Iran: Marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt
    F. Azizi, L. Mehran, R. Sheikholeslam, A. Ordookhani, M. Naghavi, M. Hedayati, M. Padyab, and P. Mirmiran

    Journal of Endocrinological Investigation, ISSN: 03914097, Pages: 422-431, Published: May 2008 Springer Science and Business Media LLC
    Objective: Two yr after legislation of salt iodization of 40 parts per million (ppm) in 1994, goiter was still endemic and urinary iodine concentration (UIC) remained elevated in many provinces of Iran. Goiter prevalence and UIC were compared 2 and 7 yr after sustained consumption of uniformly iodized salt by Iranian households. Methods: Schoolchildren (7–10 yr) of all provinces were randomly selected by cluster sampling from December 2000 to June 2001. Goiter rate, UIC, and household salt iodine values were compared to those in 1996. Factory salt iodine was also compared in 2001 vs 1996. Ultrasonographically determined thyroid volumes of 7–10 yr old children were compared in 2001 vs 1999. Results: In 2001 (no.=33600) vs 1996 (no.=36178), total, grade 1, and grade 2 goiter rates were 13.9 vs 53.8%, 11.0 vs 44.8%, and 2.9 vs 9.0%, respectively (p<0.0001). Weighted total goiter rate was 9.8% in 2001. Median (range) UIC in 2001 (no.=3329) was 165 (18–499) μg/l and in 1996 (no.=2917) was 205 (10–2300) μg/l (p<0.0001). In 2001 vs 1996, mean±SD for iodine salt content was 32.7±10.1 vs 33.0±10.2 ppm (p=0.68) in households and was 33.2±13.4 and 33.8±13.2 ppm (p=0.57) in factories, respectively. Among 7–10 yr old children in 2001 (no.=400) vs 1999 (no.=396), only 7-yr-old children in 2001 (the only group with probably no history of iodine deficiency) showed significant smaller thyroid volumes by ultrasonography compared to those in 1999. Conclusions: After 7 yr of optimized iodized-salt supplementation in Iran, adequate UIC values and marked reduction in goiter rate have been achieved.

  • Experiences in the prevention, control and elimination of iodine deficiency disorders: A regional perspective
    Eastern Mediterranean Health Journal, ISSN: 10203397, Pages: 761-770, Published: November 2004

RECENT SCHOLAR PUBLICATIONS

  • Cumulative effects of thyroid hormones over 10 years and risk of general and abdominal obesity; tehran thyroid study
    L Mehran, A Amouzegar, H Abdi, S Gharibzadeh, M Mansournia, F Azizi
    Endocrine Abstracts 70 2020

  • Serum Thyroid Peroxidase Antibody Level and Incident Hypertension in Iranian Men: A Suggestion for the Role of Thyroid Autoimmunity.
    M Tohidi, A Baghbani-Oskouei, A Amouzegar, L Mehran, F Azizi, ...
    Endocrine, Metabolic & Immune Disorders Drug Targets 2020

  • Parity and Incidence of Thyroid Autoimmunity: A Population-Based Tehran Thyroid Study
    M Takyar, M Rahmani, A Amouzegar, E Madreseh, M Tohidi, L Mehran, ...
    Thyroid 2020

  • LT4 and Slow Release T3 Combination: Optimum Therapy for Hypothyroidism?
    F Azizi, A Amouzegar, L Mehran, H Abdi
    International Journal of Endocrinology and Metabolism 18 (2) 2020

  • Isolated Hypothyroxinemia in Iranian Pregnant Women, the Role of Iodine Deficiency: A Population-Based Cross-Sectional Study
    A Etemadi, A Amouzegar, L Mehran, M Tohidi, F Azizi, K Moradi, ...
    Thyroid 30 (2), 262-269 2020

  • Smoking status and changes in thyroid-stimulating hormone and free thyroxine levels during a decade of follow-up: The Tehran thyroid study
    H Kadkhodazadeh, A Amouzegar, L Mehran, S Gharibzadeh, F Azizi, ...
    Caspian Journal of Internal Medicine 11 (1), 47 2020

  • Thyroid disease and the metabolic syndrome
    L Mehran, A Amouzegar, F Azizi
    Current Opinion in Endocrinology, Diabetes and Obesity 26 (5), 256-265 2019

  • Audit of the Congenital Hypothyroidism Screening Program in 15 Provinces of Iran
    L Mehran, S Yarahmadi, D Khalili, M Hedayati, A Amouzegar, ...
    Archives of Iranian medicine 22 (6), 310-317 2019

  • Long-Term variations of antithyroperoxidase antibodies and its clinical significance
    M Keyhanian, F Sarvghadi, L Mehran, A Amouzegar, M Beigy, M Tohidi, ...
    Hormone and Metabolic Research 51 (06), 347-352 2019

  • Evaluation of the congenital hypothyroidism screening programme in Iran: a 3-year retrospective cohort study
    L Mehran, D Khalili, S Yarahmadi, H Delshad, Y Mehrabi, A Amouzegar, ...
    Archives of Disease in Childhood-Fetal and Neonatal Edition 104 (2), F176-F181 2019

  • Tehran thyroid study (TTS)
    A Amouzegar, L Mehran, M Takyar, H Abdi, F Azizi
    International journal of endocrinology and metabolism 16 (4 Suppl) 2018

  • An Overview of Celiac Disease in Childhood Type 1 Diabetes
    I Shahramian, A Bazi, A Sargazi
    International journal of endocrinology and metabolism 16 (3) 2018

  • Secondary and tertiary preventions of thyroid disease
    F Azizi, L Mehran, F Hosseinpanah, H Delshad, A Amouzegar
    Endocrine Research 43 (2), 124-140 2018

  • Associations between thyroid and blood pressure in euthyroid adults: A 9-year longitudinal study
    H Abdi, S Gharibzadeh, E Tasdighi, A Amouzegar, L Mehran, M Tohidi, ...
    Hormone and Metabolic Research 50 (03), 236-241 2018

  • Subclinical Thyroid dysfunction and incident Cardiovascular disease: Tehran Thyroid study
    S AKBARPOUR, M TOHIDI, A AMOUZEGAR, L MEHRAN, F HADAEGH, ...
    IRANIAN JOURNAL OF ENDOCRINOLOGY AND METABOLISM (IJEM) 20 (100666), 1-9 2018

  • Thyroid dysfunction states and incident cardiovascular events: The Tehran Thyroid Study
    M Tohidi, A Derakhshan, S Akbarpour, A Amouzegar, L Mehran, ...
    Hormone and Metabolic Research 50 (01), 37-43 2018

  • The impact of iodine status on the recall rate of the screening program for congenital hypothyroidism: Findings from two national studies in Iran
    L Mehran, S Yarahmadi, D Khalili, P Nazeri, H Delshad, Z Abdollahi, ...
    Nutrients 9 (11), 1194 2017

  • Primordial and primary preventions of thyroid disease
    F Azizi, L Mehran, F Hosseinpanah, H Delshad, A Amouzegar
    International journal of endocrinology and metabolism 15 (4) 2017

  • Influence of topical iodine-containing antiseptics used during delivery on recall rate of congenital hypothyroidism screening program
    M Valizadeh, F Moezzi, Z Khavassi, M Movahedinia, S Mazloomzadeh, ...
    Journal of Pediatric Endocrinology and Metabolism 30 (9), 973-978 2017

  • Hemostasis in overt and subclinical hyperthyroidism
    A Ordookhani, KD Burman
    International Journal of endocrinology and metabolism 15 (3) 2017

MOST CITED SCHOLAR PUBLICATIONS

  • Sustainability of a well-monitored salt iodization program in Iran: marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without
    F Azizi, L Mehran, R Sheikholeslam, A Ordookhani, M Naghavi, ...
    Journal of endocrinological investigation 31 (5), 422-431 2008
    Citations: 93

  • Experiences in the prevention, control and elimination of iodine deficiency disorders: a regional perspective
    F Azizi, L Mehran
    EMHJ-Eastern Mediterranean Health Journal, 10 (6), 761-770, 2004 2004
    Citations: 87

  • Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects
    L Mehran, A Amouzegar, M Tohidi, M Moayedi, F Azizi
    Thyroid 24 (11), 1566-1574 2014
    Citations: 70

  • Establishment of the trimester-specific reference range for free thyroxine index
    F Azizi, L Mehran, A Amouzegar, H Delshad, M Tohidi, S Askari, ...
    Thyroid 23 (3), 354-359 2013
    Citations: 56

  • Eighteen years of continuously sustained elimination of iodine deficiency in the Islamic Republic of Iran: the vitality of periodic monitoring
    H Delshad, A Amouzegar, P Mirmiran, L Mehran, F Azizi
    Thyroid 22 (4), 415-421 2012
    Citations: 56

  • Trimester-specific reference ranges for thyroid hormones in Iranian pregnant women
    L Mehran, A Amouzegar, H Delshad, S Askari, M Hedayati, G Amirshekari, ...
    Journal of thyroid research 2013 2013
    Citations: 45

  • Thyroid function and metabolic syndrome: a population-based thyroid study
    L Mehran, A Amouzegar, PK Rahimabad, M Tohidi, Z Tahmasebinejad, ...
    Hormone and Metabolic Research 49 (03), 192-200 2017
    Citations: 38

  • Natural course of thyroid disease profile in a population in nutrition transition: Tehran Thyroid Study
    F Azizi, A Amouzegar, H Delshad, M Tohidi, L Mehran, Y Mehrabi
    Archives of Iranian medicine 16 (7), 0-0 2013
    Citations: 32

  • The prevalence, incidence and natural course of positive antithyroperoxidase antibodies in a population-based study: Tehran thyroid study
    A Amouzegar, S Gharibzadeh, E Kazemian, L Mehran, M Tohidi, F Azizi
    PloS one 12 (1), e0169283 2017
    Citations: 31

  • Reference limit of thyrotropin (TSH) and free thyroxine (FT4) in thyroperoxidase positive and negative subjects: A population based study
    A Amouzegar, H Delshad, L Mehran, M Tohidi, F Khafaji, F Azizi
    Journal of endocrinological investigation 36 (11), 950-954 2013
    Citations: 31

  • Screening and management of hypothyroidism in pregnancy: results of an Asian survey
    F Azizi, A Amouzegar, L Mehran, S Alamdari, I Subekti, B Vaidya, ...
    Endocrine Journal, EJ14-0083 2014
    Citations: 29

  • Does a text messaging intervention improve knowledge, attitudes and practice regarding iodine deficiency and iodized salt consumption?
    L Mehran, P Nazeri, H Delshad, P Mirmiran, Y Mehrabi, F Azizi
    Public health nutrition 15 (12), 2320-2325 2012
    Citations: 29

  • Appropriate iodine nutrition in Iran: 20 years of success
    H Delshad, L Mehran, F Azizi
    Acta Medica Iranica, 361-366 2010
    Citations: 29

  • Management of hyperthyroidism in pregnancy: comparison of recommendations of american thyroid association and endocrine society
    S Alamdari, F Azizi, H Delshad, F Sarvghadi, A Amouzegar, L Mehran
    Journal of thyroid research 2013 2013
    Citations: 28

  • The association of cigarette smoking with serum TSH concentration and thyroperoxidase antibody
    L Mehran, A Amouzgar, H Delshad, F Azizi
    Experimental and clinical endocrinology & diabetes 120 (02), 80-83 2012
    Citations: 27

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  • Marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations in Iranian schoolchildren, 10 years after universal salt iodination
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    Iranian Journal of Endocrinology and Metabolism 10 (3), 191-203 2008
    Citations: 26

  • Management of thyroid peroxidase antibody euthyroid women in pregnancy: comparison of the American Thyroid Association and the Endocrine Society Guidelines
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    Citations: 25

  • Association between thyroid hormones, thyroid antibodies and insulin resistance in euthyroid individuals: A population-based cohort
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    Citations: 23

  • Variations in serum free thyroxine concentration within the reference range predicts the incidence of metabolic syndrome in non-obese adults: a cohort study
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    Citations: 22