Search

Background.Type 2 diabetes is an increasingly common condition with several preventable microvascular complications such as kidney damage. Nephropathy is expensive to manage, especially as hospital dialysis treatment. Improving patients’ knowledge, attitude, and practice (KAP) toward their condition can achieve better control, delay complications, and improve their quality of life. This study evaluated the KAP and self-care behaviors of diabetic patients on dialysis and variables that affect it.Methods.This cross-sectional study was conducted at Shahid Beheshti academic hospitals of Tehran, Iran. Face-to-face interviews were held to fill five validated questionnaires: three evaluating KAP, one evaluating self-management, and one evaluating quality of life.Result.117 diabetic patients on hemodialysis (42 females) with mean (SD) age of68.70±9.26years were enrolled in the survey. The scores for patient’s KAP, self-care, and quality of life were59.90±11.23,44.27±8.35,45.06±12.87,46.21±10.23, and26.85±13.23, respectively. There was significant negative correlation between patients’ knowledge and attitude with their glycosylated hemoglobin level and their fasting blood sugar. There was significant correlation between patients’ knowledge and practice with their self-care activities.Conclusion.The present study suggests that patients’ KAP scores have a practical effect upon self-care behavior. This highlights the needs for effective diabetes education programs in developing countries like Iran.

Context Smoking is a global public health priority and accurate data of the local population is essential to improve the health policies against its use. Hence, this study aimed to summarize the important findings available on the prevalence of smoking and its association with non-communicable diseases, documented by one of the largest prospective community-based studies of Iran. Evidence acquisition All articles derived from the Tehran Lipid and Glucose Study (TLGS) in the last two decades, from the earliest publications until 30 January 2018 were reviewed for their findings on tobacco smoking. Results The prevalence of smoking in non-diabetic adults ≥ 20 years increased between baseline (phase I, 1999 - 2001) and follow-up (phase V, 2008 - 2011) from 25.5% to 35.4% among men and from 3.4% to 6.8% among women. In TLGS adolescents (10 - 18 years) water pipe use increased between 2003 and 2005 from 35.5% to 40.9% among boys and from 19.7% to 26.1% among girls. Regarding health hazards, smoking in men was associated with increased risk of combined impaired fasting glucose/impaired glucose tolerance [hazard ratio (HR) 1.69; confidence interval (CI) 95% 1.15 - 2.48] and hypertension (HR 1.26; CI 95% 0.98 - 1.63). Moreover, men, even smoking less than 10 cigarettes per day, were at increased risk for cardiovascular diseases by HR 2.12 (CI 95% 1.14 - 3.95). For women, the risk of chronic kidney disease dramatically increased 5.74-fold (CI 95% 2.71 - 12.15) among smokers. In the whole population, smoking contributed to 7.7% of all-cause mortality with HR 1.75 (CI 95% 1.38 - 2.22). Other health aspects of tobacco smoke, including its impact on metabolic status, thyroid function, female reproductive system and life style have also been reviewed. Conclusion Considering hazards of smoking, there is the urgency for more effective preventive measures in Iran; emphasizing the need for further local studies on the hazards of smoking with special attention to women and adolescents and the independent hazards of water pipe use.

Context Hypertension (HTN) is a well-known modifiable risk factor for cardiovascular disease (CVD), chronic kidney disease and mortality. Positive effects of blood pressure (BP) lowering for prevention of CVD and death have been documented in several meta-analyses of randomized controlled trials. Evidence acquisition This review focuses on the key findings derived from the Tehran lipid and glucose study (TLGS) papers on different aspects of BP and HTN. Results A prevalence of 23% for HTN has been reported in the TLGS population, aged ≥ 20 years. Over a decade long follow-up, the crude incidence rate (95% CI) of new-onset HTN defined as systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg, and not using antihypertensive medication was 33.63 (32.0 - 35.3) per 1000 person-years. Age, baseline SBP and body mass index were significant risk factors for development of isolated systolic HTN; regarding isolated diastolic HTN, baseline DBP and waist circumference were recognized as important risk factors whereas age, female gender and marriage were shown to be protective factors. SBP decreased significantly in both diabetic and non-diabetic participants; DBP showed a non-significant decrease in diabetic men and a statistically significant decrease in non-diabetic men. Among women, both those with and without diabetes (DM) generally experienced statistically significant decreases in DBP. Cox proportional hazard models showed that neither SBP nor DBP were associated with incident DM in the total population and in either gender, separately. All BP components were associated with CVD and all-cause mortality in the middle-aged population. Contribution of HTN to cerebrovascular events was also documented in the TLGS participants, aged ≥ 50 years. Conclusions Several important findings regarding BP/HTN have been derived from the TLGS. According to data regarding the prevalence and incidence of preHTN and HTN and their contribution to cardiovascular morbidity and mortality in the TLGS population as a representative sample of Tehranian population, it is recommended that interventions be prioritized for lifestyle modifications for the prevention and appropriate management of preHTN/HTN.

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.

Context Hypertension (HTN) is a well-known modifiable risk factor for cardiovascular disease (CVD), chronic kidney disease and mortality. Positive effects of blood pressure (BP) lowering for prevention of CVD and death have been documented in several meta-analyses of randomized controlled trials. Evidence Acquisition This review focuses on the key findings derived from the Tehran lipid and glucose study (TLGS) papers on different aspects of BP and HTN. Results A prevalence of 23% for HTN has been reported in the TLGS population, aged ≥ 20 years. Over a decade long follow-up, the crude incidence rate (95% CI) of new-onset HTN defined as systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg, and not using antihypertensive medication was 33.63 (32.0 - 35.3) per 1000 person-years. Age, baseline SBP and body mass index were significant risk factors for development of isolated systolic HTN; regarding isolated diastolic HTN, baseline DBP and waist circumference were recognized as important risk factors whereas age, female gender and marriage were shown to be protective factors. SBP decreased significantly in both diabetic and non-diabetic participants; DBP showed a non-significant decrease in diabetic men and a statistically significant decrease in non-diabetic men. Among women, both those with and without diabetes (DM) generally experienced statistically significant decreases in DBP. Cox proportional hazard models showed that neither SBP nor DBP were associated with incident DM in the total population and in either gender, separately. All BP components were associated with CVD and all-cause mortality in the middle-aged population. Contribution of HTN to cerebrovascular events was also documented in the TLGS participants, aged ≥ 50 years. Conclusions Several important findings regarding BP/HTN have been derived from the TLGS. According to data regarding the prevalence and incidence of preHTN and HTN and their contribution to cardiovascular morbidity and mortality in the TLGS population as a representative sample of Tehranian population, it is recommended that interventions be prioritized for lifestyle modifications for the prevention and appropriate management of preHTN/HTN.

The newborn screening (NBS) program for congenital hypothyroidism (CH) was launched on a national scale in Iran since 2005; we evaluated the program in 15 provinces, from 2011 to 2014.Fifteen provinces, including 17 districts, were included in the study. Aggregated data of screening, diagnosis, and management of all neonates born in each district in 2011 were retrospectively gathered and collectively analyzed.Program coverage ranged from 77 to 100% in different districts. The positive predictive value was low and widely ranged from 1.3 to 15.5. Transient congenital hypothyroidism (TCH) distribution values were over 5 mU/L in more than 3% of the population and were reported in 9 out of 17 districts. Repeated screening test due to inappropriate sampling varied from 0.9% in Lorestan to 36% in Zabol. Recall rate varied from 0.16 in Ardebil to 1.58 in Zanjan. CH incidence was high, with the highest value being observed in Zanjan (1:241 newborns). Screening age at 3-5 days from birth were highly observed in Gonabad (95.2%) and Zanjan (94.5%), with the lowest values observed in Giroft, Zabol, Kerman and Tehran. CH treatment was initiated before 40 days of age in 90.6% of cases. Survival time for TSH normalization event varied among the districts from 25 to 163 days. After withholding treatment at 3 years of age, TCH was identified in 30%-60% of hypothyroid cases.Main indicators of the screening program have reached the optimal goals defined by the Ministry of Health and Medical Education. However, high false positive rate and non-optimal neonatal TSH distribution values necessitate readdressing these challenging issues.

Vitamin D is a modulator of immune functions. Investigations on the mechanisms of vitamin D action and pathogenesis of Hashimoto's thyroiditis (HT) have revealed that vitamin D can reduce damages to thyroid cells caused by autoreactive immune cells.Totally, 48 female patients with HT disease were introduced to the study by endocrinologists. Patients were divided into two major groups of 24 individuals and treated weekly with 50,000 IU of cholecalciferol (vitamin D group) or placebo (placebo group) using oral administration for 3 months. Eventually, 17 of the 24 patients in each group finished the study. Before and after supplementation, frequencies of Th1, Th17, Th2 and Tr1 cells and mean fluorescent intensity (MFI) of the associated cytokines, including IFN-γ, IL-17, IL-4 and IL-10, were assessed using flow cytometry. Furthermore, gene expression of IL-10 was assessed using real-time PCR.Results of this study showed that cholecalciferol supplementation caused a significant decrease in Th17/Tr1 ratio. The proportion and MFI of Th1, Th2, Tr1 and Th17 cells included no significant changes in vitamin D group, compared to those in placebo group. Expression rate and MFI of IL-10 increased in both groups. This increase was higher in vitamin D group than placebo group with no significance.In this novel preliminary clinical trial study, supplementation with cholecalciferol in HT patients for 3 months changed the balance of CD4

Context Insulin can be prescribed as a monotherapy or a combined therapy with other anti-diabetic medications. In this narrative review, the authors aimed to gather data related to comparison of insulin monotherapy versus combination of insulin and other anti-diabetic treatments with regards to different outcome measures in type 2 diabetes. Evidence acquisition This study searched and focused on the most recently published systematic reviews and their references investigating issues related to the primary aim. Results The current data available on this topic is heterogeneous and suffers from low quality with respect to most combination treatments. Considering the efficacy and safety of combination therapy of insulin with older hypoglycemic agents, in general metformin and pioglitazone have the best and worst profiles, respectively. Compared to insulin monotherapy, combination of insulin and metformin is associated with better glycemic control, reduced daily insulin dose, less hypoglycemia, and weight gain; combination of insulin and pioglitazone results in greater hypoglycemia and weight gain and is associated with increased risk of edema and heart failure. Regarding sulphonylurea, there is some concern regarding hypoglycemia and weight gain. Addition of dipeptidyl peptidase-4 inhibitors to insulin seems to be beneficial with respect to glycemic control without any significant adverse effects. New drugs, including glucagon-like peptide-1 agonists and sodium glucose co-transporter 2 inhibitors, have acceptable profiles with significant benefits regarding weight reduction when added on insulin therapy. Conclusions Considering the quality and longevity of evidence, compared to insulin monotherapy, insulin combined with metformin and pioglitazone has the best and worst profiles, respectively. New anti-diabetic medications have acceptable profiles yet are expensive. It is important for clinicians to meticulously weigh the advantages of combination therapy against the possible adverse effects with each drug class in every patient, individually.

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.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.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.Optimization of management of thyroid diseases requires timely screening, prevention of progression to more sever disease, optimal medical care, and avoidance of iatrogenic conditions.

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.

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.

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.

Purpose and Methods: Hereditary vitamin D resistant rickets (HVDRR) is a rare disease that presents with signs and symptoms of rickets, alopecia, and growth retardation during the early years of life. The disease is caused by mutations in the vitamin D receptor (VDR) gene, which leads to unresponsiveness of the mutant receptor to 1-25(OH) 2 D3. The disease is transmitted as an autosomal recessive disorder and is found with equal frequency in males and females. The disease is rarely encountered and only about 100 cases are reported so far. The current paper reported the clinical and laboratory characteristics of 2 Iranian siblings with this disorder. Results and Conclusion: They presented with rickets, growth retardation, muscle weakness, hypocalcemia and alopecia totalis since early childhood, and were followed up for 27 years. Sequencing of the DNA extracted from the peripheral white blood cells showed a missense G to A mutation in exon number 4 (g.30994 G > A) that led to the methionine substitution for the naturally occurring valine at position 26 in the DNA binding domain (DBD) of the VDR.

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.

Background and Objectives: Thyroid disorders during pregnancy are important health problems worldwide. The aim of this study was to assess the knowledge of general practitioners (GPs) about thyroid disorders during pregnancy. Methods: In this cross sectional study, 120 GPs were randomly selected among participants of a continuous medical education (CME) program, entitled “practical endocrinology”. To assess the knowledge and educational requirements of GPs regarding thyroid disorders during pregnancy, a validated and localized multiple-choice questionnaire was used. Results: A total of 100 GPs completed the questionnaire. The mean age of the participants was 37.0 years, and 41.4% were men. The mean knowledge score of GPs was 39.9%. On average, the rate of correct response to questions concerning the definition, pathophysiology, diagnosis, complications, and treatment of thyroid disorders was 39.0%, 39.3%, 48.8%, 34.3%, and 44.6%, respectively. There was a significant difference in knowledge among GPs, who had and had not passed the training course on thyroid disorders. In addition, GPs who had passed continuous medical education programs obtained higher knowledge scores regarding diagnosis and treatment (P < 0.05). Conclusions: GPs attending pregnant women in Iran lack sufficient information on the pathophysiology, diagnosis, and management of thyroid disorders during pregnancy. Considering the key role of GPs in the public healthcare system, design of high-quality educational programs and development of specific educational packages about thyroid disorders and pregnancy are necessary.

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 un- necessary 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.

Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are mediated primarily through conversion of a small amount of testosterone to estradiol by the catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme). New studies suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone, either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between pharmacologic androgen use and the incidence of IS are questionable, because a significant portion of testosterone is converted to DHT. There is also insufficient evidence to reject a causal relationship between the pro-testosterone adrenal androgens and incidence of IS. Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria for androgen therapy for cerebrovascular complications are unclear. Confounding variables, including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to be considered. Information extracted from pharmacogenetic testing may aid in expounding the protective–destructive properties of neurosteroids, as well as the prognosis of androgen therapy, in particular their cerebrovascular outcomes. This investigative review article addresses relevant findings of the clinical and experimental investigations of androgen therapy, emphasizes the significance of genetic testing of androgen responsiveness towards individualized therapy in post-IS injuries as well as identifying pertinent questions.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practices in Tehranian adults, who may be at increased risk of vitamin D deficiency. This study was conducted on 572 individuals, aged ≥20 years from public health care centers in Tehran, Iran. Based on results of a literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire (D-KAP-38) with four subscales was developed: (1) general knowledge; (2) nutritional knowledge; (3) attitudes; (4) behaviors. Validity of the D-KAP-38 questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2 ± 7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by a panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. Exploratory factor analysis suggested a four-factor construct and the results of the confirmatory factor analysis indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0%, 1.1%, 2.4%, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59 ± 14.52) and nutrition knowledge had the lowest (42.58 ± 20.40), among the four sub-scales. Results confirm the initial validity and reliability of D-KAP-38 questionnaire. Further investigations in different populations are recommended.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.

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.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.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 persons, respectively. Euthyroid persistency was 93.24% during 6 years. Predictive factors for conversion to thyroid dysfunction were thyrotropin, free thyroxine and thyroid peroxidase antibody levels, sex, and smoking. Criteria for early diagnosis of hypothyroidism (i.e., sensitivity of 94% and specificity of 82%, p 0.0001) were obtained based on baseline and three-year follow-ups of thyroid function tests and thyroid peroxidase antibody. Early diagnosis of hypothyroidism was significantly associated with impaired glucose tolerance (relative risk with 3.03 [CI 1.36-6.75]; p = 0.007), high cholesterol (relative risk 2.46 [CI 1.45-4.18]; p = 0.001), obesity (relative risk 2.92 [CI 1.64-5.2]; p 0.001), and hypertension (relative risk 1.68 [CI 1.53-1.84]; p 0.04).This study shows that after a six-year follow-up in an iodine sufficient area, 6.7% of euthyroid subjects were found to progress to thyroid dysfunction, in particular subclinical hypothyroidism.

Objectives This study aimed to assess the prevalence and incidence and predictive factors of thyroid disorders (TD) in patients with impaired glucose metabolism. Methods Prevalence of TD was calculated in patients with impaired glucose metabolism compared to healthy controls, aged over 30 years in phase 1 of the Tehran Thyroid Study (TTS). Follow up assessments were conducted every 3 yrs, after which incidence of TD was calculated and its correlations with age, sex, smoking, blood pressure, body mass index (BMI), thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides and cholesterol were assessed. Results Incidence of TD among 435 diabetics, 286 prediabetics, and 989 healthy controls at baseline was 14, 18, and 21 per 1000 patients per year, respectively, being significantly lower in diabetics than that in healthy controls, a difference however that was not significant after adjusting for the variables mentioned (OR:0.64, 95% CI: 0.39–1.01). The incidence of TD in subjects with baseline serum TSH>1.94 mU/L or TPOAb≥40 IU/ml in all three groups was higher than that in patients with TSH≤1.94 mU/L or TPOAb1.94 mU/L was predictive of TD with 70% sensitivity and specificity. Baseline serum TSH (ROC area: 0.73, 95% CI: 0.68–0.77) had better predictive value than TPOAb (ROC area: 0.65, 95% CI: 0.61–0.69) for developing TD. Conclusion Incidence of TD in type 2 diabetics or prediabetics is not higher than healthy controls. It is however necessary to conduct thyroid tests in patients with TPOAb≥40 IU/ml or TSH>1.94 mU/L.

Thyroid dysfunction is linked with mortality and particular diseases. Intra-individual variability of measured thyroid function parameters may bias its association with outcomes, the so called "regression dilution" bias. Single measurements of thyroid function parameters result in underestimation of real associations between outcome rates with the "usual life-long levels" of the aforesaid parameters. The aim of this study was to examine the intra-individual variability of FT4 and TSH of study cohorts in the Tehran Thyroid Study (TTS) and to investigate the extent of the risk underestimation during the 4 phases (Ph) of TTS, with median follow-up of 4, 7, and 10 years between the Ph2-Ph1, Ph3-Ph1, and Ph4-Ph1 intervals; respectively. We estimated regression dilution ratios (RDRs) by the Rosner method of linear regression of repeated measures for FT4 and TSH. RDR1, RDR2, and RDR3 were obtained by regressing the repeated measures of the aforesaid parameters of the last 3 TTS follow-ups on the baseline measurements. Calculations showed 0.64 RDR1, 0.58 RDR2, and 0.52 RDR3 for TSH; and 0.62 RDR1, 0.57 RDR2, and 0.55 RDR3 for FT4. A single measurement-based risk estimation in the TTS was underestimated for FT4 about 61.2, 76.5, and 80.4%; and for TSH as 55.8, 73.1 and 93% after 4, 7, and 10 years of follow-up; respectively. In conclusion, using only single measurements of TSH and FT4 the association between thyroid function and outcome rates is considerably underestimated, especially after a long follow-up period.

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.

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.

OBJECTIVES: Interactions of human genes and environmental exposures play a crucial role in cancer etiology and prognosis. We investigated whether response to vitamin D3 supplementation in terms of plasma oxidative stress (OS) and apoptotic biomarkers were mediated by the vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) among breast cancer survivors. METHODS: Two hundred and fourteen women who were diagnosed with breast cancer (invasive or in situ) and had completed all treatment regimens received 4000 IU of vitamin D3 daily for 12 weeks. Anthropometric, dietary, sun exposure, physical activity, as well as laboratory assessments including plasma superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and Bcl2 were performed at enrolment and post-intervention. VDR genotyping was performed at ApaI, TaqI, FokI, BsmI, and Cdx-2. Linear regression was used to analyze whether the effect of vitamin D3 supplementation on response variables was modulated by the selected VDR SNPs. RESULTS: Linear regression analysis adjusted for age, BMI, on-study plasma 25(OH)D changes, and baseline circulating 25(OH)D indicated that the AA genotype of the ApaI on VDR was associated with greater increase and decrease in plasma Bcl2 [0.21, 95% Confidence Interval (CI) (0.03, 0.39)] and MDA [−0.68, 95% CI (−1.35, −0.02)] compared to aa respectively. This association did not remain statistically significant after correction for multiple testing. Overall, we found no statistically significant interaction of the VDR SNPs and inferred haplotypes with the circulating OS and apoptotic biomarkers except for the FokI BsmI ApaIhaplotype and circulating MDA (p-value for global score = 0.02) after multiple testing correction. CONCLUSIONS: Our findings indicate a weak interaction between the VDR haplotypes and responses of plasma OS and apoptotic biomarkers to vitamin D3 supplementation. However, further assessments of additional genes and biomarkers with longer intervention periods may further explain the complex interplay between genes and nutrients. FUNDING SOURCES: Cancer Research Center, National Nutrition and Food Technology Research Institute, and the Endocrine Research Center of Shahid Beheshti University of Medical Sciences.

Accurate assessment of thyroid status during pregnancy is vital for maternal and fetal health. Because free thyroxine (FT4) values in pregnancy vary widely between methods, assessment of total T4 (TT4) and FT4 index (FT4I) may be superior to FT4 in pregnant women. However, trimester-specific reference intervals for FT4I have not yet been established. In this longitudinal self-sequential survey, we aimed at determining the trimester-specific reference range for FT4I in healthy Iranian women with singleton pregnancies.A total of 466 healthy pregnant women were evaluated. After exclusion of women with history, ultrasonographic, or laboratory evidence of any thyroid disorder or iodine deficiency and those who were positive for thyroid autoantibodies, 152 women entered the study. Serum thyrotropin (TSH), TT4, and triiodothyronine-resine uptake were measured by an immunoassay method. Reference intervals were defined as 5th and 95th percentiles, using the bootstrap-based procedure.Mean values in the first, second, and third trimesters were 1.7±1.5, 1.9±1.8, and 1.9±1.8 mIU/L for TSH; 12.9±3, 14.4±3.1, and 13.6±3.3 μg/dL for TT4; and 12.8±3.5, 14.2±3.3, and 13.5±3.8 for FT4I, respectively. Reference intervals in the first, second, and third trimesters were as follows (respectively): 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 FT4I-8.5-19, 9.7-21, and 8.7-20.4. Serum TSH had no significant correlation with TT4. Serum TSH had a significant but weak correlation with FT4I only in the first trimester (r=-0.24, p=0.006).This study, for the first time, establishes the trimester-specific reference intervals for FT4I in a reference population of normal iodine-sufficient pregnant Iranian women.

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.

Because of their increased need for iodine, pregnant women are among the high-risk groups for iodine deficiency. The purpose of this study was to evaluate the effectiveness of an educational program on the iodine nutrition status of pregnant women.In this randomized controlled trial, 100 pregnant women were randomly selected from five healthcare centers in the southern region of Tehran, the capital of Iran. In the intervention group, pregnant women received a four-month educational program, which included two face-to-face educational sessions, using a researcher-designed educational pamphlet in the second and third trimesters, and two follow-up telephone calls. Knowledge, attitude, and practice (KAP) scores, urinary iodine concentration (UIC), and salt iodine content were assessed at baseline and four months after the intervention.At baseline, there were significant associations between knowledge and attitude (r = 0.38, p = 0.03) between practice and UIC (r = 0.28, p = 0.01) and between UIC and iodine content of salt (r = 0.24, p = 0.009). Although a significant difference was found in mean KAP scores between the two groups after the educational intervention, scores were significantly higher in the intervention group compared with controls (p 0.01). There were no significant differences in UIC and iodine content of salt between the two groups at follow-up.Despite educational intervention increasing KAP among women regarding the importance of iodine and iodized salt consumption during pregnancy, their iodine status did not improve. Considering the main socio-environmental determinants of iodine deficiency, in particular, the monitoring of salt fortification, prescribing iodine containing supplements as well as improving health literacy in pregnant women seem essential strategies.

Traditional standardization methods have been used in medical research for a long time to standardize the effect of interest for one confounder such as age. Model-based standardization extension of these methods is used when we have more than one variable produces an effect which is the population average and has marginal causal interpretation. In this paper, we discuss the most traditional model-based standardization methods that are used to estimate the marginal causal effect of exposure. We applied these methods to data from Tehran Thyroid Study and estimated the standardized effect of exposure on outcome. Based on the simulation studies, covariate standardization is preferred except when 1) we have enough information about the mechanism of exposure or 2) the outcome is rare and exposure is frequent, so propensity score standardization is suggested.

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 2, 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.

Type 2 diabetes mellitus is a common disease imposing a great economic burden to health systems. As the prevalence of type 2 diabetes in Iran has grown over the past decades, it has become necessary to evaluate the level of knowledge, attitude and practice of type 2 diabetic patients in our country for policy planning to increase the patients’ awareness of diabetes and its complications and, in the long run, decrease costs of treatment. The aim of this study was to evaluate the level of knowledge, attitude and practice of patients with diabetes and its relationship with self-managing of disease and quality of life. This study was conducted with the aim of assessing the knowledge, attitude, self-reported practice, self-care and health-related quality of life (HRQoL) among patients attending diabetes clinic of Torfeh academic hospital in Tehran, Iran, during April to June 2014. The study population comprised of 120 type 2 diabetic patients aged above 30 years receiving anti-diabetic medications visiting Torfeh’s outpatient diabetes clinic for follow-up care. Face-to-face interviews were carried out to fill five questionnaires evaluating patients’ knowledge, attitude, practice, self-care and HRQoL. Demographic characteristics were recorded at the beginning of the study. Laboratory data were extracted from patients’ most recent medical documents. Data were analyzed using Statistical Package for Social Science (SPSS) version 21. 120 type 2 diabetic patients (86 female and 34 male patients) with mean age of 55.98 ± 9.50 years were evaluated. The mean score of knowledge, attitude, practice, self-care and HRQoL was 67.99 ± 10.38, 73.43 ± 11.84, 64.69 ± 16.63, 58.22 ± 12.24 and −1.13 ± 0.6, respectively. There was a significant negative relationship between HbA1c and patients’ practice. We did not find any correlation between patients’ knowledge, attitude or practice and their HRQoL. There was a significant direct relationship between patients’ knowledge with their attitude and practice. This study observed a good level of knowledge, attitude and practice but a low level of self-care and HRQoL among patients. As knowledge and attitude have a direct relationship with practice and the number of people with diabetes continues to rise, we can help patients improve practice and decrease the burden of diabetes complications and their related expenditures by increasing their knowledge.

Nitric oxide participates in the regulation of thyroid function.The purpose of this study was to determine whether there is an association between serum nitric oxide metabolites (NOx) and free thyroxine (free T4), anti-thyroid peroxidase (anti-TPO), and thyroid-stimulating hormone (TSH) levels.Study subjects were adults, aged ≥20 years, who participated in the Tehran Thyroid Study (TTS). In a cross-sectional study, in the third phase of TTS, serum NOx concentrations were measured in 1974 adult participants; pregnant women and subjects who had chronic diarrhea, cancer, weight loss, and hospitalization within the past 3 months were excluded, as were those taking medicines that affect thyroid function; the remaining 1771 subjects were grouped according to tertiles of free T4, anti-TPO, and TSH. Spearman's correlation coefficients and multivariable linear regression analysis were used to determine the relationship between serum NOx levels and free T4, anti-TPO, and TSH.Serum NOx levels were negatively correlated with free T4 in men (r = -0.083; p = 0.029). An inverse association between the third tertile of free T4 and NOx levels was found in both non-adjusted (β = -0.095, p = 0.031) and multivariable-adjusted (β = -0.094, p = 0.039) analyses, only in men. After multivariable adjustment, the third tertile of anti-TPO was significantly associated with NOx levels in women (β = -0.067, p = 0.050).Based on the result, serum NOx concentration was found to be associated with free T4 in men and anti-TPO in women.

Background: Iodine deficiency elimination program has begun since two decades ago in Iran. This study was performed to evaluate the adequacy of iodine supplementation after 17 years of national salt iodization in the Kermanshah province.Methods: In this cross-sectional study 1200 schoolchildren aged 8 to10 year-old from Kermanshah province were randomly selected and evaluated in 2007. Goiter prevalence, urinary iodine excretion and iodine content of household salts were assessed. The results obtained were compared with those before iodization in 1996 and 2001. Results: Total prevalence of goiter was 10.8% in the province. The prevalence of grade 2 goiter was 1 and 0.7 percent in urban and rural areas, respectively. The median urinary iodine among 120 schoolchildren was 129.7 µg/L, with 17.5 % having urinary iodine excretion less than 50µg/L. 74.6% of households were using purified iodized salt, 71% of households had appropriate salt storage.Conclusions: The goiter prevalence has decreased significantly in Kermanshah, 17 years after national salt iodization. The median urinary iodine of schoolchildren was more than 100 µg /L in comparison with the results of studies conducted in 1996 and 2001 which indicates a well established IDD program in Iran.

Parathyroid hormone-related protein producing pancreatic neuroendocrine tumors have been infrequently reported. Herein, we report a case of an Iranian woman who had such a tumor during pregnancy, and gave birth to a female neonate with esophago-tracheal fistula and imperforated anus. Hypercalcemia was diagnosed at postpartum because of elevated serum calcium levels in the neonate and neurologic deterioration of the mother. Extensive literature review revealed 42 cases with pancreatic neuroendocrine tumors and hypercalcaemia. The clinical and laboratory findings of such patients are reviewed in this manuscript.

Iodine deficiency constitutes a public health problem in many countries worldwide. Fetal neurodevelopment is affected by maternal iodine intake. The aim of present study was to assess urinary iodine excretion (UIE) in the 3 trimesters of pregnancy and evaluate its association with newborn thyroid function in Tehran, an area of iodine sufficiency.Based on median urinary iodine in 3 trimesters, 138 pregnant women were divided into 2 groups with UIE150 (group I) and UIE ≥ 150 μg/l (group II). Cord blood samples of their newborns were evaluated for serum concentrations of TSH, T3, T4, free T4 (FT4), and thyroglobolin. Quartiles of UIE were also determined. Correlations between mothers' UIE and newborns' thyroid function in both groups were investigated.Fifty-two pregnant women (38%) had median UIE150 μg/l and 86 had (62%) UIE ≥ 150 μg/l. Median UIE in groups I and II in the 1st, 2nd, and 3rd trimesters were 125 and 212 μg/l, 97 and 213 μg/l, 93 and 227 μg/l, respectively. No significant difference was seen in thyroid function of newborns in the 2 groups. Mean concentrations of T4, T3, FT4, and TSH of newborn did not show significant difference in median UIE of mothers in various quartiles.This study shows that newborns, irrespective of mothers' UIE, in an area with a sustained iodine supplementation program, may not be at risk of alterations in thyroid functions.

The most controversial issue in the field of thyroid and pregnancy is whether clinicians should screen all pregnant women for thyroid disease, and the screening should be performed before pregnancy or at the first prenatal visit. This review aimed to discuss updates on the important issue of thyroid screening before conception and during pregnancy and to highlight the gap in evidence that has led to remarkable controversies on this topic. The terms “screening” AND “thyroid” AND “pregnancy” were used to search Medline for English-language papers published from 1990 to the end of January 2018. After reviewing of titles of 482 articles, we focused on high quality and important studies. With respect to the Wilson and Jungner criteria for disease screening, thyroid dysfunction screening before and during pregnancy is still a conflicting issue. Available data suggests that compared to the universal screening, the case finding screening would result in missing cases of thyroid dysfunction. The primary debate is regarding maternal, fetal and offspring benefits of treatment of mothers with subclinical hypothyroidism and/or thyroid autoimmunity. Results of few high-quality studies in this field are in favor of some benefit considering pregnancy outcomes but no significant beneficial impact on fetal and offspring outcomes. Likewise, cost-effectiveness studies support the concept of universal screening. More evidence is required to assess the advantages and disadvantages of two different screening strategies for thyroid dysfunction in pregnancy, focusing on maternal, neonatal and offspring health outcomes following diagnosis and treatment of thyroid dysfunction, especially subclinical hypothyroidism in pregnancy. Moreover, screening strategies need to be individualized for each country according to disease burden, case finding costs and available health services.

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.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.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.This study establishes the reference intervals and the optimal cutoff points for TPOAb in an iodine-sufficient population.

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.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).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.Diagnosis of MetS seems no more informative than its individual components in predicting mortality. Copyright © 2016 John WileySons, Ltd.

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.

Objective To evaluate the association between polycystic ovarian morphology (PCOM) and thyroperoxidase antibody level. Methods A cross-sectional study was undertaken of women aged 15–49 years living in one of four provinces in Iran recruited between February 2009 and November 2010. Eligible women did not have hirsutism and were eumenorrheic. All participants underwent a comprehensive interview, clinical examination, blood sampling, and ultrasonographic assessment. The serum concentration of thyroperoxidase antibodies was compared between women with and without PCOM. Results Among 491 participants, 74 (15.1%) had PCOM. In total, 11 (14.9%) women with PCOM and 61 (14.6%) women with normal morphology tested positive for thyroperoxidase antibodies. The serum concentration of thyroperoxidase antibodies was higher among women with PCOM (48.45 ± 135.74 IU/mL) than among those with normal ovarian morphology (37.99 ± 96.49 IU/mL), but the difference was not significant (P = 0.42). Conclusion Thyroperoxidase antibody levels were higher in Iranian women with PCOM than in women with normal morphology, although the difference was not significant. Larger longitudinal studies are needed to investigate whether the treatment of thyroid disorders can prevent the development of PCOM.

Background: Cushing's disease is the most prevalent cause of endogenous adrenocorticotrophic hormone hypersecretion. The aim of this study was to document the current clinical practice pattern in the management of Cushing's disease by Iranian Endocrinologists to determine their opinions and compare them with the current clinical practice guidelines. Methods: An eight-item questionnaire dealing with diagnosis, treatment and follow up of patients with Cushing's disease was developed, piloted, and sent to the members of Iranian Endocrinology Society. Results: Among 90 endocrinologists invited to participate in the survey, 76 replied. Most respondents selected overnight dexamethasone suppression test (ONDST) and assessment of 24-hour urinary free cortisol (UFC) as the best screening tests followed by midnight serum cortisol and midnight salivary cortisol. Classic high dose dexamethasone suppression test and measurement of serum ACTH were selected for localization of the primary lesion by 64.5%. The primary choice of treatment was trans-sphenoidal pituitary surgery (86.8%). For the recurrence of Cushing's disease, the preferred treatment modality was medical therapy followed by bilateral adrenalectomy, and pituitary re-surgery. In case of treatment failure after the first pituitary surgery and ketoconazole treatment, 51% chose bilateral adrenalectomy, while36.8% selected pasireotide only. Conclusion: ONDST and UFC are two most common tests used to screen an index case with signs and symptoms of hypercortisolism. The primary choice of treatment in Cushing's disease is pituitary surgery. However, medical treatment by ketokonazol is preferred for the recurrences. Pasireotide is the second alternative after bilateral adrenalectomy in case of treatment failure after pituitary surgery and ketoconazole.

The aim of the current study was to determine the effect of a daily intake of three grams of cinnamon over eight weeks on glycemic indicators, advanced glycation end products, and antioxidant status in patients with type 2 diabetes. In a double-blind, randomized, placebo controlled clinical trial study, 44 patients with type 2 diabetes, aged 57 ± 8 years, were randomly assigned to take either a three g/day cinnamon supplement (n = 22) or a placebo (n = 22) for eight weeks. We measured the fasting blood glucose, insulin, hemoglobinbA1c, homeostasis model assessment for insulin resistance (HOMA-IR), carboxymethyl lysine, total antioxidant capacity, and malondialdehyde levels at the beginning and the end of the study. Thirty-nine patients (20 in the intervention group and 19 in the control group) completed the study. After an eight-week intervention, changes in the level of fasting blood glucose, insulin, hemoglobinbA1c, HOMA-IR, carboxymethyl lysine, total antioxidant capacity, and malondialdehyde were not significant in either group, nor were any significant differences between groups observed in these glycemic and inflammatory indicators at the end of the intervention. Our study revealed that cinnamon supplementation had no significant effects on glycemic and inflammatory indicators in patients with type 2 diabetes.

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

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).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.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, P0.001) and in the WC-adjusted model with age, smoking and physical activity for men (B = -0.06, P0.01). 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; P0.01).Low FT4 was independently associated with IR in healthy euthyroid Iranian men.

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.

Some hormonal and metabolic changes may stimuli normal or neoplastic thyroid cells. Thyroid tumors discovered during pregnancy present unique challenges to both the clinician and the mother. The aim of this article is to compare American Thyroid Association (ATA) guidelines to Endocrine Society guidelines for management of thyroid tumors during pregnancy.We reviewed the section of thyroid nodules and cancer of ATA and Endocrine Society guidelines which have been published recently. Both organizations have discussed and given recommendations related to maternal and fetal aspects of thyroid nodules and cancer. Each topic from either guidelines was compared together and that recommendation which was more complete included in 4 tables.There is a high degree of similarity between these two guidelines. Both organizations have discussed and given recommendations related to maternal and fetal aspects of thyroid tumors. Regarding their similarity any of these two guidelines can be used for safe and proper management of women with thyroid tumors during pregnancy.Regarding their similarity any of these two guidelines can be used by clinicians for safe and proper management of pregnant women with thyroid nodules and cancer.

Background Thyroid hormones play an important role in lipid metabolism. Overt hypothyroidism is known to be associated with increased lipid profiles, but the effect of subclinical hypothyroidism (SCH) on lipid profile remains controversial. Objectives The aim of this study was to assess the association between thyroid disorders and serum lipid levels. Materials and methods The present study was conducted within the framework of Tehran lipid and glucose study (TLGS). Serum concentrations of TSH and FT4, cholesterol, triglycerides and HDL-C were measured in 5786 randomly selected subjects. Serum LDL was calculated according to the Friedwald formula. Results The study assessed 5154 subjects including 42.5% males and 57.5% females, with a mean age of 39.71 ± 14.2 years (ranged 20 - 90 years). Serum cholesterol was significantly higher in overt hypothyroidism in comparison to subclinical hypothyroidism (P = 0.003). Serum cholesterol, HDL -C, LDL-C and TG did not differ between subclinical hypothyroid and control groups. Among euthyroid men, serum FT4 levels were inversely correlated with serum cholesterol and TG. In euthyroid women, serum FT4 levels were correlated positively with serum HDL-C and negatively correlated with TG and TG/HDL-C ratio and TSH levels were associated negatively with, HDL-C. Conclusions No differences existed in lipid profiles between subclinical hypothyroidism and euthyroid subjects. There are correlations between serum FT4 and TSH and lipid profiles.