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1.  Spatial Analysis of Neonatal Congenital Hypothyroidism and Nitrate as an Environmental Pollutant in Isfahan Province During 2010-2013 
Thyroid absorption of iodine could be encumbered by nitrate drinking water when it is transported to the fetal thyroid gland. Therefore, nitrate potentially causes congenital hypothyroidism (CH) due to thyroid dysfunction. In this study, we have not only aimed at spatial determination of CH distribution and nitrate concentration (NC) existing in drinking water, but also we intended to evaluate the probable impact of nitrate on CH incidence.
Annual average of nitrate in drinking-water as well as number of CH infants diagnosed through the screening program were applied to determine the incidence ratio of the disease for each town (from 2010 to 2013). Afterward, Arc GIS 9.3 was used to draw choropleth maps with quantile classification. Data were entered into SPSS 16.0 and Excel 2010 software. Finally, linear regression was applied for data analysis.
The incidence rate of CH (considering transient and permanent cases) was about one in every 413 births. Khansar, Golpaygan, Naein, and Ardestan had the highest incidence rate of CH respectively. On the other hand, Tiran, Dehaghan, Khansar, and Fereydan had the highest level of nitrate drinking water. There was a strong relationship between the NC and incidence of CH in Khansar; however, this relationship was not significant (P = 0.392) in Isfahan province.
Since there was not a significant relationship between NC in drinking-water and incidence of CH through linear regression analysis, more studies should be implemented to confirm or refute our observations.
PMCID: PMC4564903  PMID: 26425331
Congenital hypothyroidism; Isfahan; Nitrate; spatial distribution
2.  Genotype and phenotype correlations in Iranian patients with hyperinsulinaemic hypoglycaemia 
BMC Research Notes  2015;8:350.
Hyperinsulinaemic hypoglycaemia (HH) is a group of clinically and genetically heterogeneous disorders characterized by unregulated insulin secretion. Abnormalities in nine different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, UCP2 and HNF1A) have been reported in HH, the most common being ABCC8 and KCNJ11. We describe the genetic aetiology and phenotype of Iranian patients with HH.
Retrospective clinical, biochemical and genetic information was collected on 23 patients with biochemically confirmed HH. Mutation analysis was carried out for the ATP-sensitive potassium (KATP) channel genes (ABCC8 and KCNJ11), GLUD1, GCK, HADH and HNF4A.
78 % of the patients were identified to have a genetic cause for HH. 48 % of patients had mutation in HADH, whilst ABCC8/KCNJ11 mutations were identified in 30 % of patients. Among the diazoxide-responsive patients (18/23), mutations were identified in 72 %. These include two novel homozygous ABCC8 mutations. Of the five patients with diazoxide-unresponsive HH, three had homozygous ABCC8 mutation, one had heterozygous ABCC8 mutation inherited from an unaffected father and one had homozygous KCNJ11 mutation. 52 % of children in our cohort were born to consanguineous parents. Patients with ABCC8/KCNJ11 mutations were noted to be significantly heavier than those with HADH mutation (p = 0.002). Our results revealed neurodevelopmental deficits in 30 % and epilepsy in 52 % of all patients.
To the best of our knowledge, this is the first study of its kind in Iran. We found disease-causing mutations in 78 % of HH patients. The predominance of HADH mutation might be due to a high incidence of consanguineous marriage in this population. Further research involving a larger cohort of HH patients is required in Iranian population.
PMCID: PMC4535259  PMID: 26268944
Hyperinsulinaemic hypoglycaemia; HADH (hydroxyacyl-CoA-dehydrogenase); Diazoxide
3.  Effect of the peels of two Citrus fruits on endothelium function in adolescents with excess weight: A triple-masked randomized trial 
Obesity induces endothelial dysfunction even in the pediatric age group. The possible protective effects of fruits and herbal products on the endothelial dysfunction of obese children remain to be determined. This study aims to investigate the effects of lemon and sour orange peels on endothelial function of adolescents with excess weight.
Materials and Methods:
This triple-masked, randomized placebo-controlled trial was conducted for 1-month among 90 overweight and obese participants, aged 6-18 years. They were randomly assigned into three groups of equal number receiving daily oral capsules containing lemon or sour orange powder or placebo. Flow-mediated dilatation (FMD) was compared between three groups by using analysis of covariance.
Overall, 30 participants in the lemon group, 27 in the sour orange group and 29 in the control group completed the trial. After the trial, mean FMD was significantly (P < 0.001) higher in the lemon group (11.99 ± 4.05) and in the sour orange group (12.79 ± 5.47) than in the placebo group (6.45 ± 2.79). FMD percent change was 145.02 ± 24.34 in the lemon group, 142.04 ± 16.11 in the sour orange group, and 46.73 ± 5.16 in controls (P < 0.001).
This trial showed that consumption of extracts of lemon and sour orange peels, which contain plenty amounts of antioxidants, flavonoids, pectin, and vitamin C, might have significant benefits on endothelial function in children and adolescents with excess weight. Trial registry code: IRCT201311201434N10.
PMCID: PMC4652303  PMID: 26664417
Childhood obesity; endothelial function; Citrus fruits; prevention
4.  Mutation of Kisspeptin 1 Gene in Children with Precocious Puberty in Isfahan City 
Considering the role of kisspeptin (KISS) in the process of puberty, this study aimed to determine the mutation of KISS1 gene among a group of patients with idiopathic central precocious puberty (ICPP).
In this case control study, a group of children with diagnosed ICPP and a group of healthy children were selected. Genomic DNA was extracted from peripheral blood of selected population. After proving the quality and quantity of extracted DNA samples by nano-drop instrument, PCR was performed using 3 set of primers to amplify all coding exons and flanking intron region of Kiss1 gene.
In this study, 33 patients with idiopathic PP and 30 control age and sex matched children were studied. Genetic analysis indicated that there was not any polymorphism or mutation in studied participants of the control group. Among patients with ICPP, 4 single nucleotide polymorphisms within the promoter and coding regions of KISS1 gene were determined in 9 patients (5 boys and 4 girls). Among them, the c.-148 T > A was novel variant.
The results of the current study identified one novel polymorphism and three reported polymorphism in KISS gene among patients with ICPP. It is recommended to design further studies for analysis other genes related to ICPP in accordance with more complementary biochemical evaluations is recommended also.
PMCID: PMC4434494  PMID: 26015864
Central precocious puberty; kisspeptin gene; mutation; polymorphism
5.  The Relationship between Perchlorate in Drinking Water and Cord Blood Thyroid Hormones: First Experience from Iran 
Considering the controversial information regarding the effects of perchlorate on thyroid function of high risk population as neonates, and given the high prevalence rate of thyroid disorders specially congenital hypothyroidism in our region, this study aims to investigate for the first time in Iran, the relationship between drinking groundwater perchlorate and cord blood thyroid hormones level in an industrial region.
In this cross-sectional study, drinking groundwater perchlorate level of rural areas of Zarinshahr, Isfahan was measured. Simultaneously, cord blood level of thyroid hormones of neonates born in the studied region was measured. Thyroid function test of neonates in regions with low and high perchlorate level were compared.
In this study, 25 tap water samples were obtained for perchlorate measurement. Level of cord blood thyroid stimulating hormone (TSH), T4 and T3 of 25 neonates were measured. Mean (standard deviation) of perchlorate, TSH, T4 and T3 was 3.59 (5.10) μg/l, 7.81 (4.14) mIU/m, 6.06 (0.85) mg/dl, and 63.46 (17.53) mg/dl, respectively. Mean levels of thyroid function tests were not different in low (<5 μg/l) and high level of drinking ground water perchlorate (P > 0.05).
Perchlorate did not appear to be related to thyroid function of neonates in the studied industrial region. It seems that iodine status of the regions, as well as other environmental contaminants and genetic background, could impact on its relation with thyroid function of neonates.
PMCID: PMC4362289  PMID: 25789149
Environment; infant; perchlorate; thyroid gland
6.  The Effect of Vitamin C on Endothelial Function of Children with Type 1 Diabetes: An Experimental Study 
Considering the importance of improvement of endothelial function in patients with type 1 diabetes mellitus (DM) and to prevent its related micro- and macro-vascular complications; in this study, the effect of vitamin C administration on improving endothelial function of children with type 1 diabetes was investigated.
In this analytic-experimental study, children with type 1 DM aged 6-18 years and a group of healthy children enrolled. Vitamin C (250 mg/daily) administrated for the two studied groups for 1-month. Endothelial function evaluated by flow-mediated dilatation (FMD) and intima-media thickness (IMT) measurement using vascular Doppler ultrasonography, before and after trial.
In this study, 18 patients with type 1 diabetes (DM) and 19 normal children as the control group were studied. After vitamin C administration IMT reduced in all studied groups (P < 0.05). FMD increased in all studied groups, but it was significant only in the control group (P = 0.02 in the control group and P = 0.07 in patients with DM). Mean differences of IMT 2 – IMT 1, FMD 2 – FMD 1 and left ventricular (LV) mass 2 – LV mass 1 and blood pressure (BP) were not significantly different in two studied groups (P > 0.05). Mean differences of IMT 2 – IMT 1, FMD 2 – FMD 1, LV mass 2 – LV mass 1 and BP were not significantly different in patients with HbA1c ≤ 7 g/dl and those with HbA1c >7 g/dl and control group (P > 0.05).
The findings of the current study indicated that vitamin C may have a protective effect on endothelial dysfunction, but regarding its effectiveness among the high-risk population such as diabetic patients with and without appropriate glycemic control the study was not sufficiently powered due to its small sample size.
PMCID: PMC4258680  PMID: 25489448
Endothelium; type 1 diabetes; vitamin C
7.  Are obese adolescents more depressed? 
Obesity is a growing problem in all countries which leads to various physical, psychological, and social problems. The present study aimed to assess depression in children and adolescents aged 10-18-year old compared with the control group.
Materials and Methods:
In a case-control study, from among the 10- to 18-year-old students of the five education districts of Isfahan, 100 people (50 girls and 50 boys) were selected as obese children with the Body Mass Index (BMI) of greater than 95th percentile for their age and gender and 100 others (50 girls and 50 boys) as the control group with the BMI of 5th to 85th percentile. The case and control groups were matched for age, gender, and socio-economic status. After calculating BMI based on weight (kg)/height2 (meter), subjects were interviewed based on DSM IV criteria to diagnose clinical depression. The severity of children's depression was measured using standardized questionnaire.
The mean age of the case group was 12.2 ± 1.86-years old and that of the control group 13.06 ± 2.25. They were, respectively, diagnosed with depression of 7% and 6%. The mean depression score of the case group was 11.7 ± 5.3 and that of the control group was 10.6 ± 6.03 with no statistical significance.
Given our findings, the Jolly fat hypothesis applies to the case group. It seems that health policy-makers need to make intervention plans to change behavior; attitude, skill, and knowledge (BASK) of the public toward obesity and its long-term side-effects.
PMCID: PMC4113990  PMID: 25077167
Adolescent; depression; obesity
8.  Absence of Association between -1131T>C Polymorphism in the Apolipoprotein APOA5 Gene and Pediatric Metabolic Syndrome 
Iranian Journal of Pediatrics  2014;24(3):319-322.
Objective: In the present study, we evaluated the association of rs662799 variant of the APOA5 gene with Metabolic syndrome (MetS) in a sample of children and adolescents from Isfahan.
Methods: This case control study comprised 50 cases of MetS and 50 controls. Mismatched polymerase chain reaction–restriction fragment length polymorphism (mPCR-RFLP) was used to genotype -1131T>C polymorphism.
Findings : No significant association was documented for APOA5 genotypes with the measured laboratory parameters for CC, CT, and TT genotypes in the two groups studied. By logistic regression using a dominant model, the odds ratio (95% confidence interval0 for the MetS was 0.38 (0.139–1.0350 and 0.29 (0.08–1.071 for the unadjusted and adjusted models, respectively.
Conclusion: This study suggests that among studied children and adolescents, -1131T>C polymorphism in the APOA5 gene may not be a major contributor to the MetS risk.
PMCID: PMC4276588  PMID: 25562027
Apolipoprotein A5 Gene; Metabolic Syndrome; Children; Adolescents; Triglyceride; Cholesterol
9.  Protein-energy Malnutrition in Goitrous Schoolchildren of Isfahan, Iran 
Some studies have shown the possible role of protein-energy malnutrition (PEM) in persistence of endemic goiter in iodine replenished areas. The present study was conducted to assess the association between PEM and goiter in schoolchildren of Isfahan, Iran.
In a cross-sectional study using multistage cluster random-sampling, 2331 schoolchildren with age ranged from 6-13 years old with a female to male ratio of 1.60 were enrolled. Thyroid size was examined by two endocrinologists for goiter detection. Children were considered goitrous if they had palpable or visible goiters according to World Health Organization (WHO)/United Nations children's Fund/International Council for the Control of Iodine Deficiency criteria. Weight and standing height were measured using the standard tools and anthropometric indices were calculated using the WHO AnthroPlus software developed by the World Health Organization. Height-for-age Z-scores (HAZ), weight-for-age Z-scores (WAZ) and body mass index (BMI) for age were calculated for each child. Children with a HAZ, WAZ or BMI-for-age of Z-score < –2.0 were classified as stunted, underweight or thin, respectively. Blood samples were drowned to measure serum thyroid hormones.
Overall, 32.9% of subjects were classified as goitrous. Weight, height, BMI, WAZ and BMI-for-age Z-score were significantly lower in children with goiter than in children who did not have goiter (P < 0.05). The prevalence of goiter in thin children was higher than that in non-thin ones (48.4 vs. 31.6%, odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.52-2.69, P < 0.001). Although 33.4% of non-stunted children were goitrous, 31% of stunted ones had goiter (P = 0.5). According to the logistic regression model taking sex and age as covariates, the only significant parameter affecting palpable goiter detection was thinness (OR = 2.13, 95% CI: 1.22-3.69, P < 0.001).
In the present study, we found a high prevalence of goiter in children who were malnourished. It seems that PEM may play a role in the still high prevalence of goiter in this region.
PMCID: PMC4050673  PMID: 24932384
Body mass index-for-age Z-score; goiter; height-for-age Z-score; Iran; protein-energy malnutrition; weight-for-age Z-score
10.  The relation between serum and filter paper TSH level in neonates with congenital hypothyroidism 
the aim of this study was to determine the relation between serum and filter paper thyroid-stimulating hormone (TSH) levels in neonates with congenital hypothyroidism (CH). We also tried to determine an appropriate cutoff point of filter TSH for recalling screened neonates.
Materials and Methods:
in this descriptive-analytic study, records of 2283 neonates who had been recalled during CH screening program in Isfahan (Iran) were studied. The relation between serum and filter paper TSH levels in the studied neonates was assessed and the best cutoff point of filter TSH and its sensitivity and specificity for proper diagnosis of CH were determined.
among the studied neonates, 103 (4.5%) were diagnosed with CH. Using receiver operating characteristic (ROC) curve, the best cutoff point for diagnosing CH was 7.5 with a sensitivity of 74.8% and specificity of 71.3%. The rates of false positive and false negative diagnoses at this cutoff point were28.7% and 25.2%, respectively. There was a significant relationship between serum and filter paper TSH levels.
the cutoff point for recall should be changed to 7.5 for appropriate screening outcome. On the other hand, considering the low cost of filter paper and importance of missing any case of CH, changing the cutoff point is not necessary. However, further studies in different parts of Iran are required to obtain more accurate results and consider all related factors.
PMCID: PMC3928837  PMID: 24592370
Congenital hypothyroidism; filter paper; thyroid-stimulating hormone
11.  Ultrasonographic evaluation of the thyroid gland volume among 8-15-year-old children in Isfahan, Iran 
Local reference data are needed in the screening of children for thyroid enlargement. We determined the thyroid gland volume using the ultrasonography (US) in schoolchildren of Isfahan, Iran.
Materials and Methods:
A total of 360 schoolchildren (59% girls) aged 8-15 years who met the study criteria were entered the study. Clinical grading of goiter was performed by an endocrinologist according to the World Health Organization (WHO) classification. Then, a single expert radiologist performed thyroid volume measurement using a portable ultrasound device. Urinary iodine (UI) concentration was checked in 36 randomly selected cases.
On physical examination, 327 (91%), 32 (8.8%) and 1 (0.2%) subjects were classified as normal, borderline and goiter Grade 2. Mean thyroid volume measured by US was 1.46 ± 0.70 ml. Thyroid volume in boys was significantly higher than girls (1.58 ± 0.67 ml vs. 1.38 ± 0.71 ml; P = 0.009). Thyroid volume was positively correlated with the clinical grade of the goiter (r = 0.30, P < 0.001) and with age (r = 0.25, P < 0.001). Both median and 95th percentile of thyroid volume of our subjects was lower than the reference values reported by WHO. Median of UI was 16.90 μg/dl. UI was not correlated with thyroid volume (r = 0.12, P = 0.46).
The thyroid size in Isfahanian schoolchildren is lower than the reference values reported by WHO. These data could be used in determining local reference in the screening of children for thyroid enlargement.
PMCID: PMC3929009  PMID: 24600596
Goiter; Isfahan; thyroid; thyroid volume; ultrasound
12.  Etiology of congenital hypothyroidism in Isfahan: Does it different? 
Considering the higher prevalence of congenital hypothyroidism (CH) in Iran and the importance of determination of the etiology of CH for assessing appropriate treatment strategies, understanding the pathogenesis of CH and the implications of its inheritance and prognosis, the aim of this study was to determine the etiology of CH 7 years after initiation of the program in Isfahan province.
Materials and Methods:
In this cross-sectional study, children with a primary diagnosis of CH studied. They clinically examined and their medical files were reviewed by a Pediatric Endocrinologist. Considering screening and follow-up lab data and radiologic findings the etiology of CH was determined. Screening properties of different etiologies of CH was compared.
In this study, 437 patients with permanent CH (PCH) were studied. Etiology of PCH in 316 (72.3%) and 121 (27.7%) of cases was thyroid dyshormonogenesis and thyroid dysgenesis, respectively. Prevalence of agenesis, ectopia, hypoplasia and hemiagenesis in thyroid dysgenetic patients was 13.3%, 6.4%, 4.3% and 3.7% respectively. Mean of thyroid stimulating hormone in screening, recall and after discontinuing treatment at 3 years of age was significantly lower in dyshormonogenetic CH patients than dysgenetic ones(P < 0.01).
Seven years of our experiences in CH screening program indicated that the etiology of CH in Isfahan, with a higher rate of CH, with a predominance of thyroid dyshormonogenesis is different from most of the studies world-wide and similar to other reports from Iran. The findings of the current study provide us baseline information for determination of CH pathogenesis in this region.
PMCID: PMC3929017  PMID: 24600601
Congenital hypothyroidism; dysgenesis; dyshormonogenesis; permanent
13.  Prevalence of Permanent Congenital Hypothyroidism in Isfahan-Iran 
Considering the importance to determine the reasons for the higher occurrence of congenital hypothyroidism (CH) in Iran, in this study we report the prevalence of permanent CH (PCH) in Isfahan province 7 years after initiation of CH screening program in Isfahan.
In this cross-sectional study, children with a primary diagnosis of CH studied. They clinically examined and their medical files were reviewed by a pediatric endocrinologist. Considering screening and follow-up lab data, radiologic findings and the decision of pediatric endocrinologists the final diagnosis of PCH was determined.
A total of 464,648 neonates screened in Isfahan province. The coverage percent of the CH screening and recall rate was 98.9% and 2.1%, respectively. A total of 1990 neonates were diagnosed with primary CH. PCH was diagnosed in 410 neonates. The prevalence of PCH and transient CH (TCH) was 1 in 1133 and 1 in 294 live births. The most common etiology of CH was thyroid dyshormonogenesis.
Though the prevalence of PCH is high, but the higher prevalence of CH in Isfahan is commonly due to cases with TCH. Hence, the necessity of determining new strategies for earlier diagnosis of patients with TCH is recommended.
PMCID: PMC3898441  PMID: 24498491
Congenital hypothyroidism; permanent; transient
14.  The effect of low glycemic index diet on body weight status and blood pressure in overweight adolescent girls: a randomized clinical trial 
Nutrition Research and Practice  2013;7(5):385-392.
Although several studies have assessed the influence of the glycemic index on body weight and blood pressure among adults, limited evidence exists for the pediatric age population. In the current study, we compared the effects of low glycemic index (LGI) diet to the healthy nutritional recommendation (HNR)-based diet on obesity and blood pressure among adolescent girls in pubertal ages. This 10-week parallel randomized clinical trial comprised of 50 overweight or obese and sexually mature girls less than 18 years of age years, who were randomly assigned to LGI or HNR-based diet. Macronutrient distribution was equivalently prescribed in both groups. Blood pressure, weight and waist circumference were measured at baseline and after intervention. Of the 50 participants, 41 subjects (include 82%) completed the study. The GI of the diet in the LGI group was 42.67 ± 0.067. A within-group analysis illustrated that in comparison to the baseline values, the body weight and body mass index (not waist circumference and blood pressure) decreased significantly after the intervention in both groups (P = 0.0001). The percent changes of the body weight status, waist circumference and blood pressure were compared between the two groups and the findings did not show any difference between the LGI diet consumers and those in the HNR group. In comparison to the HNR, LGI diet could not change the weight and blood pressure following a 10-week intervention. Further longitudinal studies with a long-term follow up should be conducted in this regard.
PMCID: PMC3796664  PMID: 24133618
Glycemic index; obesity; blood pressure; adolescent; obese
15.  Prevalence of transient congenital hypothyroidism in central part of Iran 
Congenital hypothyroidism (CH) considered a common endocrine disorder in Iran. We report the epidemiologic findings of CH screening program in Isfahan, seven years after its development, regarding the prevalence of transient CH (TCH) and its screening properties comparing with permanent CH (PCH).
Materials and Methods:
In this cross-sectional study, children with primary diagnosis of CH were studied. Considering screening and follow-up lab data and the decision of pediatric endocrinologists, the final diagnosis of TCH was determined.
A total of 464,648 neonates were screened. The coverage percent of the CH screening and recall rate was 98.9 and 2.1%, respectively. Out of which, 1,990 neonates were diagnosed with primary CH. TCH was diagnosed in 1,580 neonates. The prevalence of TCH was 1 in 294 live births. 79.4% of patients with primary CH had TCH. Mean of screening (54.7 ± 59.0 in PCH vs 21.8 ± 28.9 in TCH), recall (56.5 ± 58.8 in PCH vs 36.6 ± 45.0 in TCH), and thyroid stimulating hormone (TSH) and mean of TSH before (2.0 ± 2.9 in PCH vs 1.6 ± 1.6 in TCH) and after (37.7 ± 29.5 in PCH vs 4.3 ± 1.9 in TCH) discontinuing treatment at 3 years of age was significantly higher in PCH than TCH (P < 0.0000).
The higher rate of CH in Isfahan is mainly due to the transient form of the disease. Further studies for evaluating the role of other environmental, autoimmune and/or genetic factors in the pathophysiology of the disease is warranted.
PMCID: PMC3872610  PMID: 24379847
Congenital hypothyroidism; permanent; transient
16.  Influence of perinatal factors on thyroid stimulating hormone level in cord blood 
The aim of the present study was to determine the effect of various perinatal factors on cord blood TSH among newborns in Isfahan, Iran.
Materials and Methods:
This was a descriptive–analytic cross sectional study which performed in Isfahan Iran. During a period of four months, since February to May 2012 a total number of 440 newborns delivered in Alzahra and Shahid beheshti hospitals were enrolled in the study. For all newborns one mL blood sample from umbilical vein was obtained by one of the project investigators and sent to laboratory for further examinations. Cord blood TSH and birth body weight (BBW), gestational age, history of gestational diabetes mellitus (GDM), apgar at one minute, apgar at five minute, newborn gender and the mother's age were documented. Differences considered statistically significant if P < 0.01.
440 newborns enrolled in the study, 221 (50.2%) were male and 219 (49.8%) were female. Among study parameters, method of delivery had statistically significant relation with cord blood TSH (P < 0.001), and other factors such as BBW, gestational age, GDM, apgar at one minute, apgar at five minute, newborn gender and the mother's age didn’t have statistically significant relationship with cord TSH level.
In conclusion we deduce that the only factor that can affect cord blood TSH was method of delivery. Infant with vaginal delivery has higher TSH level in cord blood. Other factors that were evaluated in this study didn’t have any statistically significant relationship.
PMCID: PMC3905335  PMID: 24516848
Cord blood; perinatal factors; thyroid stimulating hormone
17.  Intelligence quotient in children with congenital hypothyroidism: The effect of diagnostic and treatment variables 
Considering the high prevalence of congenital hypothyroidism (CH) in Isfahan, the intelligence quotient (IQ) of children with CH and the effect of diagnostic and treatment variables on it were investigated during the CH screening program.
Materials and Methods:
A total of 120 children in three studied groups were studied in this comparative study the IQ score, in three subsets of verbal IQ, performance IQ and full scale IQ, of children diagnosed with transient congenital hypothyroidism (TCH) and permanent congenital hypothyroidism (PCH) was measured using revised Wechsler pre-school and primary scale of intelligence and compared with the control group. The relation between IQ score with time of treatment initiation and screening thyroid stimulating hormone (TSH) level was evaluated in all studied groups.
Mean of verbal IQ, performance IQ, and full scale IQ score was significantly higher in the control group than CH patients (both permanent and transient) In PCH patients though it was not significant, there was a negative relationship between verbal IQ, performance IQ and full scale IQ and screening TSH and age of treatment initiation. In TCH patients, there was negative and significant relationship between verbal IQ (r = −0.40) and full scale IQ (r = −0.38) and age of treatment initiation (r = −0.46).
Mean IQ score in both PCH and TCH patients were lower than the control group, which correlates negatively with treatment initiation time. Though CH screening and early treatment has improved the prognosis of patients, but early and high dose of treatment in children with CH is recommended.
PMCID: PMC3810573  PMID: 24174944
Congenital hypothyroidism; intelligence quotient; permanent; transient; Wechsler pre-school and primary scale
18.  Growth and Specialized Growth Charts of Children with Congenital Hypothyroidism Detected by Neonatal Screening in Isfahan, Iran 
ISRN Endocrinology  2013;2013:463939.
Objectives. The aim of the current study was to investigate the growth status of CH, generate specialized growth charts of CH infants, and compare them with their counterparts of regional normal infants. Methods. In this prospective cohort study, 760 (345 girls and 415 boys) neonates born in 2002–2009 diagnosed by neonatal CH screening program in Isfahan were followed up from the time of diagnosis. 552 healthy children were recruited as a control group. The empirical 3rd, 15th, 50th, 85th, and 97th percentiles for height, weight, and head circumference of both sexes were determined and compared with their counterpart values of the control group. The relative frequency of patients with impaired growth for each studied variable was determined. Also, specialized growth charts of CH patients were generated. Results. The percentiles of weight, height, and head circumference of studied patients are significantly different from regional healthy children (P < 0.001). The relative frequency of impaired head circumference was decreased to less than 3% at the 3rd year of age and for height it reached gradually 3% and 9% at the 5th year of age for boys and girls, respectively (P < 0.05); however for weight still it was statistically more than 3% in both sexes. Conclusion. CH patients had impaired growth development which was improved during follow up, but the catch-up time was earlier for head circumference and later for weight.
PMCID: PMC3582096  PMID: 23476799
19.  Prevalence and related risk-factors of peripheral neuropathy in children with insulin-dependent diabetes mellitus 
Diabetes mellitus (DM) is a common metabolic disorder that can cause various complications including, peripheral neuropathy (PNP). Some possible risk-factors such as blood glucose level, hyperglycemia, duration of diabetes, and lipid profiles are assumed to be important in diabetic PNP incidence. The aim of this study is to evaluate the prevalence and possible risk-factors of PNP in children with insulin dependent DM.
Materials and Methods:
Among diabetic children, 146 patients (up to 18-years old) were evaluated in this cross-sectional study. All patients were examined for signs and symptoms of neuropathy and nerve conduction studies were performed. Blood level of glucose and lipid profiles were also tested. The relation between variables was compared by independent t-test and logistic regression test.
The mean age of diabetic children was 11.9 ± 3.3 years whereas mean diabetes duration was 3.8 ± 2.9 years. PNP was detected in 40 patients (27.4%) that 62.5% of them have subclinical and 37.5% have clinical neuropathy. According to logistic regression analysis, duration of diabetes was the most important factor in prevalence of PNP (5.7 ± 3.5 and 3.1 ± 2.5 years in patients with and without neuropathy respectively, P < 0.001, 95% confidence interval [1.15-1.54]).
As most of the patients had subclinical PN, neurological assessment is recommended to detect subclinical neuropathy in asymptomatic type 1 diabetic children and it seems that the best way to prevent this complication is still rigid blood glucose control and periodic evaluations.
PMCID: PMC3724374  PMID: 23914216
Diabetes mellitus; peripheral neuropathy; prevalence; risk factors; type 1
20.  The G395R Mutation of the Sodium/Iodide Symporter (NIS) Gene in Patients with Dyshormonogenetic Congenital Hypothyroidism 
Considering the high prevalence of congenital hypothyroidism (CH) in Isfahan and its different etiologies in comparison with other countries, the high rate of parental consanguinity, and the role of NIS gene in permanent CH due to dyshormonogenesis, the aim of this study was to investigate the G395R mutation of the NIS gene in patients with permanent CH due to dyshormonogenesis
In this case–control study, patients diagnosed with permanent CH due to dyshormonogenesis during CH screening program were selected. Venous blood sample was obtained to determine the G395R mutations of NIS gene using polymerase chain reaction (PCR) sequencing method.
In this study, 35 CH patients with permanent CH due to dyshormonogenesis and 35 neonates with normal screening results as a control group were studied. We did not find any changes of the mentioned mutation of NIS gene in the patients’ group.
Considering the findings of the current study, it seems that further studies with larger sample size and with consideration of other gene mutations such as pendrin and thyroglobulin are needed for more accurate conclusion.
PMCID: PMC3570912  PMID: 23412840
Congenital hypothyroidism; dyshormonogenesis; G395R; mutation; sodium/iodide symporter (NIS) gene
21.  Different Aspects of Kidney Function in Well-Controlled Congenital Hypothyroidism 
Objective: Congenital hypothyroidism (CH) increases the prevalence of kidney and urogenital malformations. There are limited studies considering different aspects of kidney function in well-controlled CH patients. We evaluated some features of kidney function in euthyroid children with CH who have been receiving thyroxine hormone since early life.
Methods: This cross-sectional study was conducted in Isfahan, Iran, on 74 children aged 2-15 years old (36 CH patients and 38 healthy children). Inclusion criteria for CH patients were euthyroidism at the time of the survey and initiation of replacement therapy during the early neonatal period. Kidney ultrasound evaluation was performed in all participants. Serum biochemistry included urea, creatinine, sodium (Na), potassium (K), magnesium, calcium, and cystatin C levels. Urine electrolytes, fraction excretion (FE) of electrolytes and microalbumin, and glomerular filtration rate (GFR) were also determined.
Results: The male/female ratio was 0.8/1 and 1.5/1 in the patient and control groups, respectively. Mean age and height did not differ significantly between the two groups. Ultrasound evaluation of the kidney revealed that the anteroposterior diameter of the right kidney was significantly higher in CH patients as compared to healthy subjects. No significant difference was observed between GFRs in patients with CH and healthy children. The mean values for FENa and FEK were significantly higher in the patient group.
Conclusions: Increased FENa and FEK may be a manifestation of impaired tubular maturation in CH. More longitudinal studies are needed to evaluate kidney function in CH patients.
Conflict of interest:None declared.
PMCID: PMC3537285  PMID: 23261862
congenital hypothyroidism; kidney function; kidney size
22.  Changes in serum lipid profile of obese or overweight children and adolescents following a lifestyle modification course 
ARYA Atherosclerosis  2012;8(3):143-148 .
Considering rapid global increase in children obesity and high prevalence of dyslipidemia in obese and overweight children, this study aimed to evaluate the effect of an educational course on changes of lipid profile in children.
This non-pharmacological clinical trial study was performed on 4-18 year-old children attending outpatient clinics of Isfahan Endocrine and Metabolism Research Center (Iran). Anthropometric measurements were conducted for all children. Fasting blood samples were taken from right hand of the participants at the first laboratory visit. Biochemical tests including measurement of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were also carried out. Children took part in one educational session in which they were taught about ways and benefits of having regular physical activity once a day and having healthy foods. All children were followed up for about four months and anthropometrics and biochemical tests were repeated. Data was analyzed using SPSS16.
A total number of 412 children (245 girls and 167 boys) were divided into four age groups of under 6, 6-9, 10-13, and 14-18 years old. Baseline anthropometric measures were significantly higher in boys. However, there was no difference between boys and girls in baseline lipid profile. Children's body mass index (BMI) z-score increased in all age groups except for 14-18 year-old boys. In boys older than 10 years, there were significant reductions in LDL-C and TC. In girls over 10 years of age, there was a significant increase in HDL-C. Although anthropometric measurements did not change in children (except for 14-18 year-old-boys), there was a significant reduction in children's lipid profile after the study.
Our study showed that although one session of interventional education had no significant effects on children's anthropometric measurements, it could change their lipid profile. Moreover, the intervention was more effective on improving lipid profile in children over 10 years of age. Therefore, effective interventional strategies must be invented and implemented on children based on their age group.
PMCID: PMC3557010  PMID: 23359278
Children Obesity; Education; Anthropometry; Lipid Profile; Lifestyle
23.  High prevalence of congenital hypothyroidism in Isfahan: Do familial components have a role? 
Despite elimination of iodine deficiency, the rates of both permanent and transient congenital hypothyroidism (CH) in our study were higher than the comparable worldwide rates, which emphasize the major role of genetic factors in the pathogenesis of CH and many studies in this regard confirm this possibility.
Materials and Methods:
In this review, we report all studies that established during CH screening program regarding familial and genetic component of the disease.
Although we could not entirely ignore the possible role of environmental and autoimmune factors in the development and function of thyroid gland, our findings strongly suggest the role of genetic factors as dominant etiologic factor in CH.
The studies support the existence of a familial component of CH involving dominant genetic predisposition factors with a low penetrance. Considering the polygenic/multifactorial basis of CH, they suggest the possible involvement of other unknown genes in the pathogenesis of the disease, which may also follow non-Mendelian pattern of inheritance.
PMCID: PMC3544130  PMID: 23326768
Congenital hypothyroidism familial; dysgenesis; dyshormonogenesis; genetic
24.  Hearing Impairment in Congenitally Hypothyroid Patients 
Iranian Journal of Pediatrics  2012;22(1):92-96.
Thyroid hormone is necessary for normal development of the auditory system. The aim of this study was to investigate the rate of hearing impairment in congenitally hypothyroid (CH) patients, and its relation with factors such as CH severity and age at starting treatment, during CH screening program in Isfahan.
Hearing acuity was assessed in two groups of children with (94 patients aged 4 months – 3 years) and without CH (450), between 2000-2006. Otoacostic emission (OAE) was performed by a two step method. After two tests without OAE signals bilaterally, they were referred for auditory brainstem response (ABR) test. Subjects with both OAE and ABR abnormal test results were considered to have hearing problem. Obtained data was compared in case and control group and also CH patients with and without hearing impairment.
Three (3.2%) of patients and 1 of control group (0.2%) were diagnosed with sensorineural hearing loss. The rate of hearing loss was not different significantly in two studied groups (P>0.05). There was no difference between age of starting treatment and first T4 and TSH level in CH patients with and without hearing loss (P>0.05). CH neonates with hearing impairment had thyroid dyshormonogenesis according to the follow up results.
The rate of hearing loss was low among our studied CH patients. It may be due to proper management of CH patients. In view of the fact that all CH neonates were dyshormonogentic and considering the relation between certain gene mutations and hearing impairment in CH patients, further studies with larger sample size, with regard to different etiologies of CH should be investigated to indicate the possible gene mutations related to hearing loss in CH.
PMCID: PMC3448222  PMID: 23056865
Hearing impairment; Auditory Brain Stem Response; ABR; Oto Acostic Emission; OAE
25.  Effect of education on anthropometric indices in obese parents and children after one year of follow-up 
ARYA Atherosclerosis  2012;8(1):21-26.
Childhood obesity has reached epidemic levels. Children obesity predisposes them to risk of cardiac disease in adulthood. Environmental factors, lifestyle preferences, and cultural environment play pivotal roles in the rising prevalence of obesity worldwide. Furthermore, family life style has a great influence on children obesity. This study aimed to determine the effect of family-oriented weight reduction program on the children’s anthropometric measurements.
This was a non-pharmacological clinical trial study which was performed on 4-18 years old children attending outpatient clinics of Isfahan Endocrine and Metabolism. Anthropometric measurements were recorded for all the participants. Children took part in one educational session in which they were taught about ways and benefits of having a regular physical activity each day and also benefits of having healthy nutrition. All the participants took part in every 4 months one-hour educational sessions and their anthropometrics were measured.
Fifty eight single-mother families participated in this study. Fourteen single-father families started the intervention but did not follow it to the end. Children’s body mass index (BMI) z-score decreased significantly after the study. Children waist circumference (WC) and hip circumference (HC) significantly increased. Mothers WC and waist to hip ratio (WHR) increased significantly. Regression test showed that mother BMI was an independent factor (B = 0.307; P < 0.021). The effect of the pattern of children’s BMI changed across a one-year period.
Our study showed significant effect of repetitive family life style education on children’s BMI z-score changes. Family, as the first place for children behavior formation, must be regarded as one of the best place to tackle childhood obesity.
PMCID: PMC3448397  PMID: 23056096
Children Obesity; Parents; Life Style Intervention; Education; Anthropometric Indices

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