Pheochromocytoma and renal agenesis

Pheochromocytomas are cathecolamine producing tumor arising from chromaffin cells of adrenal medulla and extra adrenal tissues. Renal anomalies have been reported rarely in this disease. Here we report a rare case of pheochromocytoma associated with renal agenesis. Patient was a boy presented with headache and hypertension. In radiologic examinations, an adrenal mass was detected in the left side, with no renal tissue on that side. It was reported an adrenal pheochromocytoma in histopathology. Renal agenesis confirmed during surgery. All of the patients symptoms alleviated after the resection of tumor. Considering association of renal abnormalities with pheochromocytoma, it is recommended to perform genetic analysis and kidney evaluation in cases with MEN type 2 or each of its components. © 2008 Tehran University of Medical Sciences. All rights reserved

Erythrocyte susceptibility to oxidative stress and antioxidant status in patients with type 1 diabetes

In this study, malondialdehyde (MDA) level as an index of erythrocyte susceptibility to oxidative stress and antioxidant defense system (glutathione level (GSH), glutathione peroxidase enzyme activity (GPx) in erythrocytes and ferric reducing ability of plasma (FRAP) as the total plasma antioxidant capacity were measured in 35 patients with type 1 diabetes and 28 age and sex-matched normal subjects. MDA level was significantly elevated in diabetic patients (650.9 ± 144.3 nmol/g versus 476.5 ± 138.5 nmol/g Hb, P < 0.001). The level of MDA was positively correlated with duration of diabetes (r = 0.29, P < 0.05) and HbA1C (r = 0.39, P < 0.05) and negatively with FRAP (r = -0.3, P < 0.05). The level of GSH and FRAP were lower in patients than controls (7.05 ± 1.6 μmol/g versus 8.24 ± 0.9 μmol/g Hb, and 389.05 ± 82.3 μmol/l versus 520.4 ± 124.1 μmol/l, respectively, P < 0.001). GPx activity was not significantly different between the two groups. GSH and FRAP were negatively correlated with HbA1C (r = -0.334, P < 0.01 and r = -0.5, P < 0.01, respectively). In conclusion, there seems to be an increased susceptibility to oxidative stress and decreased antioxidant defense in patients with type 1 diabetes, which may be due to poor glycemic control. © 2007 Elsevier Ireland Ltd. All rights reserved

Total and acylated ghrelin levels in children and adolescents with idiopathic short stature and poor appetite

Context. Ghrelin is a hormone secreted primarily from stomach that can affect growth by its somatotropic and orexigenic activities. Objective. The aim of this study was to investigate the relationship of ghrelin and growth in children and adolescents with idiopathic short stature. Subjects and Methods. After thorough clinical examination, 56 subjects including 31 with normal weight and height and 25 with short stature were evaluated for fasting total (TG) and acylated (active) ghrelin (AG) levels. All the parameters of growth including growth hormone and IGF-1 levels, bone age and body mass index were also investigated. Appetite was also assessed and all the studied subjects were also divided into two groups, poor or good appetite. Results. TG and AG levels were not significantly different in the two groups. There was not any significant correlation between ghrelin and parameters of growth. On the other hand, TG concentration was significantly higher in subjects with poor appetite, but AG was not significantly different. Conclusions. The results of this study show that ghrelin is not significantly altered in idiopathic short stature. Although TG is increased in children with poor appetite its acylation is not increased concomitantly. © 2015, Editura Academiei Romane. All rights reserved

Clinical and hormonal milieu of 9 patients with primary growth hormone insensitivity syndrome and their response to IGF-I generation test

Primary growth hormone insensitivity syndrome (GHIS) is a rare entity which can be due to defects in growth hormone (GH) receptor that is called type 1 Laron syndrome (T1LS) or post receptor defects (type 2 Laron syndrome ). The aim of study was determining the clinical and hormonal milieu of the patients with primary GHIS and their response to IGF-I (insulin like growth factor-I) generation test (IGT). GH, IGF-I, IGF-II, IGF binding protein 1 and 3 (BP-1 and BP-3), GH binding protein (GHBP) and anti-GH antibody were detected by ELISA and RIA methods. IGF-I and BP-3 were measured before and after IGT. Nine patients (8 males, 1 female) (mean age ± SD, 6.4 ± 5 years) with severe short stature and high GH level were studied. Height SDS was - 8.5 ± 2.6. In 7 patients GHBP was zero, IGF-I and BP-3 were low and did not increase after IGT, so they had T1LS. Two brothers did not show the hormonal milieu of GH receptor defect, and were called non Laron syndrome (NLS). Birth weight in patients with T1LS and NLS was 3.65 ± 0.2 Kg and 1.65 ± 0.2 Kg, respectively (P = 0.001). All of the patients had typical clinical feature of GH-deficiency, but nasal bridge depression and microphallus were not seen in NLS. GH treatment of NLS, normalized their growth velocity, but without catch up growth. In conclusion IGT can differentiate Laron syndrome from other types of short stature. GH and IGF-I of fetus have no role in intrauterine growth. © 2006 Tehran University of Medical Sciences. All rights reserved

Recurrent hepatitis in two iranian children: A novel (Q166R) mutation in EIF2AK3 leading to wolcott-rallison syndrome

Early-onset diabetes, liver dysfunction, growth retardation, spondyloepiphyseal dysplasia, and tendency to skeletal fractures due to osteopenia are characteristics of Wolcott-Rallison syndrome (WRS). Eukaryotic translation initiation factor 2α kinase (EIF2AK3) is the only known gene, which is responsible for this rare autosomal recessive disorder. Here, we report two siblings a girl and a boy with diabetes mellitus (DM) who presented in one and two months of age respectively. Recurrent self-limiting hepatitis developed later, and severe hepatic failure resulted in death of the first child. The second child visited was a 7.75 year old boy who had spondyloepiphyseal dysplasia and subclinical hypothyroidism besides DM and recurrent hepatitis. We suggested WRS for this patient, and it was confirmed by identification of a novel homozygous missense mutation (Q166R) in exon 3 of the EIF2AK3 gene. The aim of this report is to remind the possibility of WRS in isolated neonatal diabetes; while, the other clinical manifestations of this syndrome including its major symptom of recurrent hepatitis may appear later. © 2013, Kowsar Corp

Comparison of psychological health in mothers of diabetic and Leukemic children and control group

Background: Parents' psychological health is one of the most important factors to obtain health in children with chronic disease. Objectives: In this paper, we intended to evaluate and compare psychological health in parents of type 1 diabetes mellitus (T1DM) and Leukemic children with control group and estimate the effect of the type of disease on parents' psychological health and if possible recommend means to improve it. Patients and Methods: Three groups of mothers (30 people per group) were evaluated. T1DM children's mothers, Leukemic children's mothers, and control group were chosen from mothers of children who came to Hazrat Aliasghar Emergency Room without any underlying diseases. The samples were asked to fill SCL-90-R and FBIS questionnaires. In addition, other forms were filled for their demographic characteristics. Results: The abbreviation (GSI) score in Leukemic children's mothers was higher than T1DM children's mothers and both groups had higher GSI compared with the control group. Conclusions: Parental functioning and wellbeing are important aspects of a family adaptation to chronic pediatric conditions. Moreover, psychological interventions were recommended to patients. © 2015, Iranian Society of Pediatrics

The association of plasma levels of miR-34a and miR-149 with obesity and insulin resistance in obese children and adolescents

Context. MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression that influence various cellular functions including glucose and lipid metabolism and adipocyte differentiation. Objective. The aim of this study was to evaluate the levels of miR-34a and miR-149 and their relationship with metabolic parameters in obese children and adolescents. Design. Seventy children and adolescents were enrolled in the study. Plasma levels of microRNAs were evaluated by real-time PCR using SYBR green and analyzed by �Ct method. Plasma concentrations of visfatin and insulin were measured by ELISA method. Glucose and lipid profile were determined colorimetrically. HOMA-IR was calculated and used as an index of insulin resistance (IR). Results. miR-34a was significantly lower in subjects with insulin resistance compared to obese children with normal insulin sensitivity. There was an inverse relationship between miR-34a levels and both insulin and HOMA-IR. On the other hand, miR-149 was significantly correlated with visfatin. There was no significant difference in miR-34a and miR-149 between obese and normal weight subjects. Conclusions. miR-34a is associated with insulin and HOMA-IR and thus seems to be involved in IR. miR-149 is inversely associated with visfatin levels which could be indicative of anti-inflammatory effect of this miRNA. © 2018, Acta Endocrinologica Foundation. All rights reserved

Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

Objective: Congenital hyperinsulinism (CHI) is the most frequent cause of severe and persistent hypoglycaemia from birth. Understanding the pathophysiology and genetic defects behind hyperinsulinism and its complications provides clues to timely diagnosis and management. The aim of this study was to evaluate the underlying genetic aetiology of a specific Iranian pediatric cohort with CHI. Methods: A total of 44 unrelated children, 20 girls and 24 boys, with an initial diagnosis or history of CHI from all regions of Iran were recruited between 2016 and 2019. Targeted next generation sequencing (tNGS) was performed for the genes found in about half of CHI patients. Results: Mutations were identified in 24 cases (55%). Patients with a confirmed genetic cause were mainly diagnosed below age of one year old (p=0.01), had fewer other syndromic features, excluding seizure, (p=0.03), were less diazoxide responsive (p=0.04) and were more diazoxide unresponsive leading to pancreatectomy (p=0.007) compared to those with no identified mutations. Among 24 patients with identified genetic mutations, 17 (71%) had a mutation in ABCC8, 3 (12%) in KCNJ11, 3 (12%) in HADH, and 1 patient had a mutation in KMT2D. These included five novel mutations in ABCC8, KCNJ11, and KMT2D. Conclusion: This is the biggest genetic study of CHI in Iran. A high frequency of recessive forms of CHI, especially HADH mutations, in our study could be due to a high rate of consanguineous marriage. We recommend tNGS to screen for all the CHI genes.Wellcome Trust [108101/Z/15/Z]; Diabetes UK RD Lawrence fellowship (grant: 17/0005594)

Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 deficiency

Mutations in 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) cause an extraordinarily rare autosomal recessive disorder, apparent mineralocorticoid excess (AME). AME is a form of low renin hypertension that is potentially fatal if untreated. Mutations in the HSD11B2 gene result either in severe AME or a milder phenotype (type 2 AME). To date, ∼40 causative mutations have been identified. As part of the International Consortium for Rare Steroid Disorders, we have diagnosed and followed the largest single worldwide cohort of 36 AME patients. Here, we present the genotype and clinical phenotype of these patients, prominently from consanguineous marriages in the Middle East, who display profound hypertension and hypokalemic alkalosis. To correlate mutations with phenotypic severity, we constructed a computational model of the HSD11B2 protein. Having used a similar strategy for the in silico evaluation of 150 mutations of CYP21A2, the disease-causing gene in congenital adrenal hyperplasia, we now provide a full structural explanation for the clinical severity of AME resulting from each known HSD11B2 missense mutation. We find that mutations that allow the formation of an inactive dimer, alter substrate/coenzyme binding, or impair structural stability of HSD11B2 yield severe AME. In contrast, mutations that cause an indirect disruption of substrate binding or mildly alter intramolecular interactions result in type 2 AME. A simple in silico evaluation of novel missense mutations could help predict the often-diverse phenotypes of an extremely rare monogenic disorder

A validated normative model for human uterine volume from birth to age 40 years

Transabdominal pelvic ultrasound and/or pelvic Magnetic Resonance Imaging are safe, accurate and non - invasive means of determining the size and configuration of the internal female genitalia. The assessment of uterine size and volume is helpful in the assessment of many conditions including disorders of sex development, precocious or delayed puberty, infertility and menstrual disorders. Using our own data from the assessment of MRI scans in healthy young females and data extracted from four studies that assessed uterine volume using transabdominal ultrasound in healthy females we have derived and validated a normative model of uterine volume from birth to age 40 years. This shows that uterine volume increases across childhood, with a faster increase in adolescence reflecting the influence of puberty, followed by a slow but progressive rise during adult life. The model suggests that around 84% of the variation in uterine volumes in the healthy population up to age 40 is due to age alone . The derivation of a validated normative model for uterine volume from birth to age 40 years has important clinical applications by providing age-related reference values for uterine volume.Publisher PDFPeer reviewe