Weight fluctuation, mortality, and cardiovascular disease in adults in 18 years of follow-up: Tehran Lipid and Glucose Study.

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

Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS).

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

Appropriate duration of antithyroid drug treatment as a predictor for relapse of Graves' disease: a systematic scoping review.

BACKGROUND: Following the conventional 12-18 month antithyroid drug (ATD) treatment in Graves' disease (GD), 50% of patients experience relapse of hyperthyroidism. OBJECTIVE: The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80 years. METHODS: Articles were identified through the search of PubMed from January 1, 1941 to April 30, 2021. All study types were included. Articles were eligible if they reported data on the length of ATD treatment, particularly thyroid hormones and TSH receptor antibodies (TRAb) concentrations and specifically those with data on the remission and/or relapse rates. RESULTS: We described major progress regarding the duration of ATD therapy and related outcomes at every 20 years. Articles of 1941-1960 were mainly concerned with determination of favorable treatment, minimal effective dose, side effects and rate of remission after < 12-month ATD therapy. Studies with larger number of patients and longer follow-ups appeared in 1961-1980; higher remission rate after 18-24 months versus 6 months of ATD therapy was reported. Articles of 1981-2000 focused on identification of factors associated with high relapse rates after discontinuation of ATD. In 2001-2021, ATD became the first choice of treatment in many countries. However, 12-18 months of ATD therapy was arbitrarily chosen as the appropriate option. According to recent studies, persistent normalization of TRAb occurs after 5 years of methimazole therapy and ATD treatment of > 60 months could offer a 4-year remission rate of 85%. CONCLUSION: Long-term ATD treatment for more than 60 months is safe and effective, has the highest remission rate and cures most patients with GD; hence, it should be considered as the most appropriate duration for ATD therapy in these patients.

TPO antibody in euthyroid pregnant women and cognitive ability in the offspring: a focused review.

PURPOSE: A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. METHOD: Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. RESULTS: There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. CONCLUSION: Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy.

Virus-Host Protein-Protein Interactions between Human Papillomavirus 16 E6 A1 and D2/D3 Sub-Lineages: Variances and Similarities.

High-risk strains of human papillomavirus are causative agents for cervical and other mucosal cancers, with type 16 being the most frequent. Compared to the European Prototype (EP; A1), the Asian-American (AA; D2/D3) sub-lineage seems to have increased abilities to promote carcinogenesis. Here, we studied protein-protein interactions (PPIs) between host proteins and sub-lineages of the key transforming E6 protein. We transduced human keratinocyte with EP or AA E6 genes and co-immunoprecipitated E6 proteins along with interacting cellular proteins to detect virus-host binding partners. AAE6 and EPE6 may have unique PPIs with host cellular proteins, conferring gain or loss of function and resulting in varied abilities to promote carcinogenesis. Using liquid chromatography-mass spectrometry and stringent interactor selection criteria based on the number of peptides, we identified 25 candidates: 6 unique to AAE6 and EPE6, along with 13 E6 targets common to both. A novel approach based on pathway selection discovered 171 target proteins: 90 unique AAE6 and 61 unique EPE6 along with 20 common E6 targets. Interpretations were made using databases, such as UniProt, BioGRID, and Reactome. Detected E6 targets were differentially implicated in important hallmarks of cancer: deregulating Notch signaling, energetics and hypoxia, DNA replication and repair, and immune response.

Maternal Thyroid Function and Autoimmunity in 3 Trimesters of Pregnancy and their Offspring's Thyroid Function.

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.

The Association Between Blood Pressure and Normal Range Thyroid Function Tests in a Population Based Tehran Thyroid Study.

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.

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

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.

Prevalence of hypothyroidism in patients with dyslipidemia: Tehran Thyroid Study (TTS).

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.

Local versus international recommended TSH references in the assessment of thyroid function during pregnancy.

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.

Reference limit of thyrotropin (TSH) and free thyroxine (FT4) in thyroperoxidase positive and negative subjects: a population based study.

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.

Management of thyroid peroxidase antibody euthyroid women in pregnancy: comparison of the american thyroid association and the endocrine society guidelines.

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.

The incidence of thyroid function abnormalities and natural course of subclinical thyroid disorders, Tehran, I.R. Iran.

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

The association of cigarette smoking with serum TSH concentration and thyroperoxidase antibody.

BACKGROUND: Although 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. AIM: 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. SUBJECTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

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

Experiences in the prevention, control and elimination of iodine deficiency disorders: a regional perspective.

Before 1987, iodine deficiency was not considered an issue of major importance in the countries of the Eastern Mediterranean Region (EMR). Progress began with a systematic national study of goitre and other iodine deficiency disorders (IDD) in the Islamic Republic of Iran in 1983. Following a major review of the prevalence of IDD in member states, Guidelines for national programmes for the control of iodine deficiency disorders in the EMR were published by the World Health Organization (WHO) in 1988. This paper discusses progress towards elimination of iodine deficiency by reviewing the status of IDD in the countries of EMR and programmes for prevention and control of IDD with particular reference to the Islamic Republic of Iran, the first country to be declared IDD-free by WHO.

Experiences in the prevention, control and elimination of iodine deficiency disorders: a regional perspective

Before 1987, iodine deficiency was not considered an issue of major importance in the countries of the Eastern Mediterranean Region [EMR]. Progress began with a systematic national study of goitre and other iodine deficiency disorders [IDD] in the Islamic Republic of Iran in 1983. Following a major review of the prevalence of IDD in member states, Guidelines for national programmes for the control of iodine deficiency disorders in the EMR were published by the World Health Organization [WHO] in 1988.This paper discusses progress towards elimination of iodine deficiency by reviewing the status of IDD in the countries of EMR and programmes for prevention and control of IDD with particular reference to the Islamic Republic of Iran, the first country to be declared IDD-free by WHO