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1.  Protein-energy Malnutrition in Goitrous Schoolchildren of Isfahan, Iran 
Background:
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.
Methods:
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.
Results:
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).
Conclusions:
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
2.  Glycemic index, glycemic load and childhood obesity: A systematic review 
Background:
Several evidences have been reported so far in terms of the relationship between obesity and glycemic index and glycemic load in children. However, the number of review studies that have dealt with recent findings is quite low. The purpose of present study is to review the existing evidences in this regard.
Materials and Methods:
First of all, the phrases: “Glycaemic index”, “Glycaemic load”, “Glycemic index” OR “Glycemic load” accompanied by one of the words: “Adolescent”, “Young”, “Youth” “Children” OR “Child” were searched in texts of articles existing in ISI and PUBMED databases which were obtained out of 1001 articles. Among these, some articles, which reviewed the relationship of obesity with glycemic index and glycemic load, were selected. Finally, 20 articles were studied in current review study.
Results:
The majority of cross-sectional studies have found children's obesity directly linked with glycemic index and glycemic load; however, cohort studies found controversial results. Also, the intervention studies indicate the negative effect of glycemic index and glycemic load on obesity in children.
Conclusion:
Published evidences reported inconsistent results. It seems that existing studies are not sufficient and more studies are needed in this regard.
doi:10.4103/2277-9175.125757
PMCID: PMC3949335  PMID: 24627855
Children; glycemic index; glycemic load; obesity
3.  The relation between serum and filter paper TSH level in neonates with congenital hypothyroidism 
Background:
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.
Results:
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.
Conclusion:
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.
doi:10.4103/2277-9175.124663
PMCID: PMC3928837  PMID: 24592370
Congenital hypothyroidism; filter paper; thyroid-stimulating hormone
4.  Ultrasonographic evaluation of the thyroid gland volume among 8-15-year-old children in Isfahan, Iran 
Background:
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.
Results:
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).
Conclusion:
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.
doi:10.4103/2277-9175.124637
PMCID: PMC3929009  PMID: 24600596
Goiter; Isfahan; thyroid; thyroid volume; ultrasound
5.  Etiology of congenital hypothyroidism in Isfahan: Does it different? 
Background:
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.
Results:
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).
Conclusion:
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.
doi:10.4103/2277-9175.124658
PMCID: PMC3929017  PMID: 24600601
Congenital hypothyroidism; dysgenesis; dyshormonogenesis; permanent
6.  Prevalence of Permanent Congenital Hypothyroidism in Isfahan-Iran 
Background:
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.
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, radiologic findings and the decision of pediatric endocrinologists the final diagnosis of PCH was determined.
Results:
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.
Conclusions:
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
7.  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.
doi:10.4162/nrp.2013.7.5.385
PMCID: PMC3796664  PMID: 24133618
Glycemic index; obesity; blood pressure; adolescent; obese
8.  Prevalence of transient congenital hypothyroidism in central part of Iran 
Background:
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.
Results:
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).
Conclusion:
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
9.  Influence of perinatal factors on thyroid stimulating hormone level in cord blood 
Background:
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.
Results:
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.
Conclusion:
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.
doi:10.4103/2277-9175.114189
PMCID: PMC3905335  PMID: 24516848
Cord blood; perinatal factors; thyroid stimulating hormone
10.  Intelligence quotient in children with congenital hypothyroidism: The effect of diagnostic and treatment variables 
Background:
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.
Results:
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).
Conclusion:
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
11.  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.
doi:10.1155/2013/463939
PMCID: PMC3582096  PMID: 23476799
12.  Prevalence and related risk-factors of peripheral neuropathy in children with insulin-dependent diabetes mellitus 
Background:
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.
Results:
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]).
Conclusion:
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
13.  The G395R Mutation of the Sodium/Iodide Symporter (NIS) Gene in Patients with Dyshormonogenetic Congenital Hypothyroidism 
Background:
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
Methods:
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.
Results:
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.
Conclusion:
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
14.  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.
doi:10.4274/Jcrpe.811
PMCID: PMC3537285  PMID: 23261862
congenital hypothyroidism; kidney function; kidney size
15.  Changes in serum lipid profile of obese or overweight children and adolescents following a lifestyle modification course 
ARYA Atherosclerosis  2012;8(3):143-148 .
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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
16.  High prevalence of congenital hypothyroidism in Isfahan: Do familial components have a role? 
Background:
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.
Results:
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.
Conclusion:
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.
doi:10.4103/2277-9175.100130
PMCID: PMC3544130  PMID: 23326768
Congenital hypothyroidism familial; dysgenesis; dyshormonogenesis; genetic
17.  Thyroid Peroxidase Gene Mutation in Patients with Congenital Hypothyroidism in Isfahan, Iran 
Background. Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis in patients with congenital hypothyroidism (CH). In this study, the prevalence of TPO gene mutations in patients with thyroid dyshormonogenesis in Isfahan was investigated. Methods. In this cross-sectional study, genomic DNA of 41 patients with permanent CH due to thyroid dyshormonogenesis was extracted using the salting out method. The 17 exonic regions of the TPO gene were amplified. SSCP technique was performed for scanning of the exonic regions of the TPO gene, except exon 8. DNA sequencing was performed for those with different migration patterns in SSCP by chain termination method. Exon 8 was sequenced directly in all patients. In 4 patients, all fragments were also sequenced. Results. One missense mutation c.2669G > A (NM_000547.5) at exon 15 (14th coding exon) in one patient in homozygous form and seven different single nucleotide polymorphisms (SNPs) in exons 1, 7, 8, 11, and 15 of TPO gene. Conclusion. The TPO gene mutations among CH patients with dyshormonogenesis in Isfahan were less frequent in comparison with other similar studies. It may be due to the presence of other unknown gene mutations which could not be detected by SSCP and sequencing methods.
doi:10.1155/2012/717283
PMCID: PMC3419406  PMID: 22919382
18.  A Case of Congenital Lipoid Adrenal Hyperplasia 
Lipoid congenital adrenal hyperplasia (lipoid CAH), a rare disorder of steroid biosynthesis, is the most severe form of CAH. In this disorder the synthesis of glucocorticoids, mineralocorticoids and sex steroids is impaired which result in adrenal failure, severe salt wasting crisis and hyperpigmentation in phenotypical female infants irrespective of genetic sex. In this report, we presented a 28-day-old phenotypic female infant, which referred with lethargy, failure to thrive and electrolyte abnormalities. Considering the clinical and biochemical findings, lipoid CAH was diagnosed and replacement therapy with standard doses of glucocorticoid and mineralocorticoid and sodium chloride was initiated. During follow-up, she had good clinical condition, but at 6 years of age, she refers with hypertension and adrenal insufficiency because of arbitrary drug discontinuation by mother. In ultrasonography an abdominal mass (the testicles) was reported. Chromosome study showed 46XY pattern. Orchiectomy was performed. We recommended that in cases with clinical presentation of adrenal insufficiency if there is not the facility to determine the karyotype, repeated ultrasonography perform during follow-up. In addition, investigating the genetic bases of the disorder would help us to determine the pathogenesis of lipoid CAH in our community. It would be helpful in prenatal diagnosis and treatment of the disorder to prevent its related comorbidities.
PMCID: PMC3415193  PMID: 22891154
46XY; failure to thrive; lipoid congenital adrenal hyperplasia
19.  Hearing Impairment in Congenitally Hypothyroid Patients 
Iranian Journal of Pediatrics  2012;22(1):92-96.
Objective
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.
Methods
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.
Findings
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.
Conclusion
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
20.  Effect of education on anthropometric indices in obese parents and children after one year of follow-up 
ARYA Atherosclerosis  2012;8(1):21-26.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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
21.  The Role of Maternal Thyroid Stimulating Hormone Receptor Blocking Antibodies in the Etiology of Congenital Hypothyroidism in Isfahan, Iran 
Background:
Considering the role of maternal thyroid stimulating hormone (TSH) receptor blocking antibody (TRAb) in the etiology of congenital hypothyroidism (CH), this study aimed to determine TRAb among patients with CH in Isfahan, Iran.
Methods:
In this case–control study, patients with CH and their mothers were compared with a group of healthy neonates and their mothers. Venous blood samples were obtained for measurement of TRAb using enzyme-linked immunosorbent assay (ELISA) method among mothers and their neonates. TSH of mothers was also determined.
Results:
The case group consisted of 65 patients with CH and their mothers; controls were 148 healthy neonates and their mothers. The prevalence of positive TRAb in patients with CH and their mothers was higher than in the control group (81.5% vs. 1.3% in mothers and 80% vs. 0% in neonates, respectively, P<0.05). The relationship between the TRAb and occurrence of CH was significant (P<0.05), whereas the corresponding figure was not significant for TRAb and the level of maternal and neonatal TSH in case and control groups (P>0.05).
Conclusion:
It seems that autoimmunity has an important role in the etiology of CH. Further studies are necessary to determine other autoantibodies in CH patients.
PMCID: PMC3278878  PMID: 22347610
Congenital hypothyroidism; etiology; thyroid stimulating hormone receptor blocking; autoimmunity
22.  Thyroid Disorders in Children and Adolescents with Type 1 Diabetes Mellitus in Isfahan, Iran 
Iranian Journal of Pediatrics  2011;21(4):502-508.
Objective
Studies in different populations have shown great variation in the prevalence of thyroid diseases in patients with type 1 diabetes mellitus (T1DM). Our aim was to study the prevalence of thyroid disorders such as autoimmunity of thyroid (AIT), thyroid dysfunction, and goiter in children and adolescents with T1DM, compared with age- and sex-matched healthy controls in Isfahan.
Methods
One hundred patients with T1DM who were referred to Isfahan Endocrine and Metabolism Research Center and 184 healthy schoolchildren matched for age and sex were included. They were examined for goiter by two endocrinologists. Thyroid function test and serum thyroid antibodies (anti-TPO Ab and anti-Tg Ab) were measured.
Findings
The prevalence of subclinical hypothyroidism was high in both groups (18%). T1DM patients had lower frequency of goiter (21% vs. 38%, P=0.001), and higher prevalence of positive AIT (22% vs. 8%, P=0.001), anti-TPO Ab positivity (19.3% vs. 5.3%, P=0.000), and anti-Tg Ab (11.1% vs. 6.4%, P=0.1) in comparison with the control group. Being positive for AIT in diabetic patients meant an odds ratio of 5 (CI 95%: 1.5-15.6) for thyroid dysfunction. There was no association between age, sex, duration of diabetes and HbA1C with serum anti-TPO Ab and anti-Tg Ab concentrations in this group.
Conclusion
Our results demonstrated the high prevalence of AIT and thyroid dysfunction in patients with T1DM. We suggest regular thyroid function and antibody testing in these patients.
PMCID: PMC3446149  PMID: 23056839
Type 1 diabetes mellitus; Autoimmune thyroid disease; Thyroid dysfunction disease; Goiter; Thyroid antibody
23.  The role of ultrasonography in primary congenital hypothyroidism 
BACKGROUND:
The aim of this study was to compare the usefulness of ultrasonography and scintigraphy in diagnosing the etiology of primary congenital hypothyroidism (CH).
METHODS:
The newborns that were examined by both thyroid scintigraphy and ultrasonography during CH screening program in Isfahan were included in this study. The ultrasonographic findings were compared with the scintigraphic findings and the sensitivity and specificity of the ultrasonography was determined.
RESULTS:
During this study, 102 CH newborns were studied. According to the ultrasonographic results, 61.8%, 26.5%, 2.9% and 8.8% of them had normal thyroid gland, agenesia, ectopia and hypoplasia, respectively, and according to scintigraphic results, 55.9%, 35.3% and 8.8% of them had normal thyroid gland, agenesia and ectopia, respectively. Ultrasound detected sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratio were 77%, 92%, 89%, 84%, 9.6 and 0.25, respectively. The sensitivity and specificity of ultrasonography compared with thyroid scintigraphy in diagnosis of thyroid gland ectopia was 33% and 100%, respectively.
CONCLUSIONS:
Though thyroid ultrasonography failed to diagnose 67% of ectopic cases and nonfunctioning thyroid gland, it had the ability to determine the anatomy of thyroid gland. So, considering some limitations of scintigraphy, we concluded that ultrasonography is a relatively appropriate imaging tool for diagnosing CH etiologies, especially in the initial phase of CH screening.
PMCID: PMC3430036  PMID: 22973380
Congenital Hypothyroidism; Etiology; Iran; Radioisotope Scanning; Ultrasonography
24.  A Case of Atypical McCune-Albright Syndrome with Vaginal Bleeding 
Iranian Journal of Pediatrics  2011;21(3):399-403.
Background
McCune-Albright syndrome (MAS) is a rare non-inherited disorder characterized by the clinical triad of precocious puberty, cafe-au-lait skin lesions, and fibrous dysplasia of bone.
Case Presentation
We report a girl with MAS, presenting initially with vaginal bleeding at the age of 17 months. Ultrasonography revealed unilateral ovarian cysts and ureteral and ovarian enlargement. Considering the clinical and paraclinical findings, the patient diagnosed as a case of gonadotropin-independent precocious puberty was treated with medroxy-progestrone acetate (MPA) for three months. During the follow up, recurrent episodes of bleeding, ovarian activation and cyst formation, as well as breast size development were reported. At the age of 5.5 years, fibrous dysplasia was detected, which in coexistence with precocious puberty confirmed the diagnosis of MAS. The patient had no cafe-au-lait skin macles during follow up.
Conclusion
Considering that clinical manifestations of MAS appear later in the course of recurrent periods of ovarian activation and cyst formation, a careful clinical observation and follow up of patients is necessary and the diagnosis of MAS must be kept in mind in cases with gonadotropin-independent precocious puberty.
PMCID: PMC3446187  PMID: 23056821
McCune-Albright Syndrome; Bleeding; Fibrous Dysplasia of Bone; Precocious Puberty
25.  Anthropometric indices associated with dyslipidemia in obese children and adolescents: a retrospective study in isfahan 
ARYA Atherosclerosis  2011;7(1):31-39.
BACKGROUND
Central obesity is an important risk factor for cardiovascular diseases (CVD). Preventive interventions from childhood are necessary due to the increasing prevalence of childhood obesity. Body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and waist to height ratio (WSR) are anthropometric indices for measurement of obesity. This study aimed to assess the association between these anthropometric indices and dyslipidemia in obese children and adolescents.
METHODS
This retrospective study was done on the records of 2064 obese children and adolescents aged 6-18 years at the obesity clinic, in Isfahan Cardiovascular Research center. Age, gender, weight, height, WC, hip circumference (HC), triglyceride (TG), total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), Fasting blood sugar (FBS), diastolic blood pressure (DBP) and systolic blood pressure (SBP) were taken from patients’ record. Receiver operating characteristics (ROC) curve and Pearson correlation were used to analyze the data.
RESULTS
2064 girls and boys aged 6-18 years were divided into 3 age groups of 6-9.9 years, 10-13.9 years and 14-18 years. Prevalence of high LDL-C, TC, TG, FBS, SBP, DBP and low HDL-C was higher among the boys compared to the girls. There was a significant association between TC, LDL-C, TG and FBS with BMI, WC, WHR and WSR. However, no significant correlation was seen between HDL-C and the four anthropometric indices.
CONCLUSION
Our study showed a significant correlation between BMI, WC and WSR with high levels of TC, TG and LDL-C in children and adolescents. Correlation between WHR and dyslipidemia in this study was significant but its predictive value was weaker than other three indices.
PMCID: PMC3347839  PMID: 22577442
Body Mass Index; Waist Circumference; Waist to Hip Ratio; Waist to Height Ratio; Dyslipidemia; Children; Adolescents

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