Sonographic cortical bone thickness measurement: can it predict bone mineral density in the pediatric population?

PURPOSE: To explore sonographic cortical bone thickness (CoT) as a potential indicator of bone mineral density (BMD) measured by dual-energy X-ray absorptiometry for screening and diagnosing pediatric osteoporosis. METHODS: A prospective study included 41 osteopenic or osteoporotic patients and 52 healthy children. Radius cortical thickness (R-CoT), tibial cortical thickness (T-CoT), and second metatarsal cortical thickness (M-CoT) were measured by B-mode ultrasound; CoT values were compared between groups and the correlation between BMD and CoT was examined. RESULTS: There were no significant differences in R-CoT (P = 0.433), T-CoT (P = 0.057), and M-CoT (P = 0.978) values between the patient and control groups. No significant correlations were found between BMD T-scores and R-CoT (r = -0.073, P = 0.490), T-CoT (r = -0.154, P = 0.141), and M-CoT (r = 0.047, P = 0.657) values. CONCLUSION: Sonographic CoT values in children do not correlate with BMD values. Unlike in adults, sonographic CoT measurements do not appear to have a role in assessing BMD in the pediatric population.

A case of prohormone convertase deficiency diagnosed with type 2 diabetes.

Prohormone convertase 1/3, encoded by the proprotein convertase subtilisin/kexin type 1 gene, is essential for processing prohormones; therefore, its deficiency is characterized by a deficiency of variable levels in all hormone systems. Although a case of postprandial hypoglycemia has been previously reported in the literature, prohormone convertase insufficiency with type 2 diabetes mellitus has not yet been reported. Our case, a 14-year-old girl, was referred due to excess weight gain. She was diagnosed as having type 2 diabetes mellitus based on laboratory test results. Prohormone convertase deficiency was considered due to the history of resistant diarrhea during the infancy period and her rapid weight gain. Proinsulin level was measured as >700 pmol/L(3.60-22) during diagnosis. In genetic analysis, a c.685G> T(p.V229F) homozygous mutation in the PCSK1 gene was detected and this has not been reported in relation to this disorder. In conclusion, patients with recurrent resistant diarrhea during infancy followed by rapid weight gain need to be evaluated with the diagnosis of prohormone convertase deficiency.

Corneal Biomechanical Properties in Childhood Obesity.

PURPOSE: To investigate corneal biomechanical properties in patients with childhood obesity. METHODS: The study included 47 patients with childhood obesity (study group) and 39 healthy patients (control group). Corneal hysteresis, corneal resistance factor, corneal compensated intraocular pressure (IOPcc), and Goldmann-correlated IOP (IOPg) were measured with the Ocular Response Analyzer (Reichert, Ophthalmic Instruments, Buffalo, NY) in each eye. Central corneal thickness (CCT), anterior chamber angle (ACA), anterior chamber volume (ACV), and anterior chamber depth (ACD) measurements were obtained by the Pentacam rotating Scheimpflug camera (Oculus Optikgeräte GmBh, Wetzlar, Germany). RESULTS: The mean corneal hysteresis was 10.56 ± 1.52 mm Hg in the study group and 11.16 ± 1.92 mm Hg in the control group (P = .022). The mean IOP was 14.9 ± 2.0 mm Hg in the study group and 14.1 ± 1.3 mm Hg in the control group (P = .003). Corneal hysteresis showed a significant, positive correlation with corneal resistance factor (P < .001, r = 0.851), IOPg (P = .044, r = 0.213), CCT (P < .001, r = 0.477), and IOP (P = .005, r = 0.295). Corneal hysteresis showed a significant, negative correlation with IOPcc (P = .001, r = -0.355), ACA (P = .005, r = -0.294), ACV (P = .019, r = -0.246), and ACD (P = .046, r = -0.211). CONCLUSIONS: Patients with childhood obesity have lower corneal hysteresis and higher IOPcc measurements when compared with healthy patients. Corneal tissue changes may occur in early life in childhood obesity, which could lead to ocular disease in the future. [J Pediatr Ophthalmol Strabismus. 2020;57(2):103-107.].

Gastrointestinal symptoms in pediatric patients with type 1 diabetes mellitus.

Background Various gastrointestinal (GI) symptoms are associated with diabetes. Common GI complaints associated with the manifestation of the disease include abdominal pain, diarrhea, nausea, bloating and vomiting. There have been very few studies examining GI problems of pediatric patients with type 1 diabetes mellitus (T1DM). The aims of this study were to find out the prevalence of GI symptoms in pediatric patients with T1DM and to determine the correlation among such symptoms, duration of diabetes and glycemic control. Methods One hundred and thirty-seven (median age 13.2 years, female 45.3%) patients with T1DM were examined. Demographic features, GI symptoms, signs and physical examination findings of the patients were recorded by pediatric gastroenterology specialists for the differential diagnosis and exclusion of other etiologies. Complete blood count, blood glucose, lipid profile, electrolytes, amylase, lipase, celiac antibodies and glycated hemoglobin (HbA1c) levels were evaluated and stool examination was performed. Endoscopy was performed on the patients who had refractory GI complaints. Gastric emptying (GE) time was evaluated using GE scintigraphy. Results Overall, 74 (54%) patients had ≥1 GI complaints. Patients often reported gastroesophageal reflux (32.8%) and abdominal pain (18%). The most significant findings in terms of GI symptoms were determined when patients were classified according to the glycemic control status. Reflux and dyspeptic symptoms were significantly more common in poorly or very poorly controlled diabetic patients (p=0.003 and p=0.004, respectively). Conclusions Diabetes can affect the entire GI tract, and GI symptoms are common in pediatric patients. We recommend that T1DM patients be evaluated for GI symptoms.

Oxidative stress markers, trace elements, and endocrine disrupting chemicals in children with Hashimoto's thyroiditis.

In this study, we aimed to investigate whether bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) exposure have any association with Hashimoto's thyroiditis (HT) and its biomarkers and to determine whether oxidative stress biomarkers and trace element levels showed any alterations in children with HT. We found that superoxide dismutase and glutathione peroxidase activities are lower in HT group from control (24% and 46%, respectively, p < 0.05). Zinc levels were significantly lower in HT group vs. control. In addition, the levels of mono-(2-ethylhexyl) phthalate (MEHP) which is the primary metabolite for DEHP, were markedly higher in HT group compared to control (p < 0.05). A negative correlation was observed between urinary BPA levels and fT4. In children with HT, oxidant/antioxidant balance is changed and these differences may be related by EDC exposure, the importance of which should be elucidated with further studies.

A Novel Mutation in the AVPR2 Gene Causing Congenital Nephrogenic Diabetes Insipidus

Objective: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by a renal insensitivity to arginine vasopressin (AVP). In the majority of the cases, CNDI is caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a novel mutation in the AVPR2 gene causing CNDI in a 6-year-old boy, presenting with growth failure and dull normal cognitive functions. Methods: The proband was the third off-spring of non-consanguineous parents and had polyuria (4.3 L/day), polydipsia (5 L/day). The diagnosis of CNDI was established by a water-deprivation test and a desmopressin challenge test. Genetic studies were also carried out in the mother, siblings and affected family members, since excessive fluid intake and diuresis were also reported in these individuals. All exons of the AVPR2 gene for all participants were amplified and sequenced. Bioinformatics analysis for wild-type and mutant AVPR2 were obtained with Swiss-Model and UCSF Chimera 1.10.2. Results: A novel, hemizygous, missense mutation was identified at the position 80th in exon 2 (p.H80Y) of AVPR2 in the proband. The proband's mother, maternal aunt and grandmother were heterozygous and his maternal uncle was hemizygous for this mutation. Bioinformatic analysis indicates this mutation would cause significant conformational changes in protein structure. Conclusion: p.H80Y mutation will cause inappropriate folding of the protein compromising water homeostasis via AVPR2 and AVP and leading to diabetes insipidus. We suggest that future functional investigations of the H80Y mutation may provide a basis for understanding the pathophysiology of the NDI in patients with this variant.

Evaluation of neurodevelopment of children with congenital hypothyroidism by the Denver Developmental Screening Test.

BACKGROUND: Thyroid hormones are essential for growth and brain development in childhood. Although congenital hypothyroidism (CH) is the most common reason for mental retardation, normal neurological development can be achieved through early and effective treatment. The aim of the present study was to evaluate the neurological development of CH patients aged 24-56 months. METHODS: The study included a total of 116 healthy control subjects and 112 patients aged 24-56 months who were diagnosed with CH during the neonatal period and were being followed up at the Pediatric Endocrinology Department, Keçiören Training and Research Hospital, between 2012 and 2015. Demographics and clinical data of interventions and outcomes were retrieved for each patient. Statistical analysis was performed using an unpaired Student's t-test to compare means and χ2-analysis to compare proportions. RESULTS: There were no significant differences between the CH and control groups with respect to gestational age, birth weight, height standard deviation scores (HSDS) and body weight standard deviation scores (BWSDS) (p>0.05). When the groups were compared according to the Denver Developmental Screening Test (DDST), no significant differences were found in terms of personal-social, fine motor skills, or language development (p=0.325, p=0.087 and p=0.636, respectively). However, a significant difference was found between the two groups with respect to gross motor development and the result of the DDST (p=0.001). No statistical difference was found between the control and patient groups on the day of starting treatment but the number of patients with an abnormal result in the DDST starting treatment at >15 days was found to be significantly higher than the number of patients starting treatment ≤15 days. No associations were found between the DDST results of the CH group and the following factors: initial L-thyroxine (LT4) level, initial LT4 dose and the onset of treatment. CONCLUSIONS: The findings of this study indicate that the DDST results in patients with CH are generally good. Initiating treatment immediately after diagnosis and during the first days of life is absolutely imperative. However, in contrast to timing, we could not find strong evidence for determining the precise optimal dosage of LT4 to initiate treatment in children diagnosed with CH. Both the American Academy of Pediatrics and the European Society for Pediatric Endocrinology recommend 10-15 µg/kg/day as the initial dose.

Choroidal Thickness in Childhood Obesity.

BACKGROUND AND OBJECTIVE: To evaluate the effects of obesity on choroidal thickness (CT) in childhood. PATIENTS AND METHODS: Forty-four patients with obesity (study group) and 42 healthy children (control group) were enrolled in the study. Subjects underwent a complete ocular examination. The mean CT was measured by enhanced depth imaging optical coherence tomography (EDI-OCT). Body mass index (BMI) was calculated. RESULTS: Mean BMI value was 31.8 ± 1.9 in the study group and 19.8 ± 4.4 in the control group. The mean subfoveal CT value 385.77 µm ± 6.09 µm in the study group and 348.43 µm ± 73.21 µm in the control group. There was a significant difference between the study and control groups with regard to subfoveal CT (P = .017). Subfoveal CT and BMI were positively correlated (r = 0.288; P = .004). CONCLUSIONS: CT increases in childhood obesity. Findings revealed that adiposity causes a significant increase in CT, and it may be related to ocular complications. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:10-17.].

Ocular manifestations of Type 1 diabetes mellitus in pediatric population.

CONTEXT: To evaluate the necessity of ocular screening in Type 1 diabetes mellitus (DM). AIMS: This study aims to investigate the diabetes-related ocular changes according to the glycosylated hemoglobin (HbA1c) level and duration of diabetes in children and compare the results with nondiabetic healthy children. SETTINGS AND DESIGN: Observational cross-sectional study designed by ophthalmology and pediatric endocrinology clinics. SUBJECTS AND METHODS: Forty-two children with Type 1 DM, 42 healthy gender- and age-matched children as controls were enrolled. All patients underwent ophthalmic and physical examination, with a review of medical history and current medication. HbA1c level, best corrected visual acuity, intraocular pressure (IOP), central corneal thickness (CCT), tear break-up time (BUT), Schirmer test, dilated fundus examination findings, central retinal thickness (CRT), and total macular volume (TMV) measurements were noted. STATISTICAL ANALYSIS: Descriptive statistics, Student's t-test, Mann-Whitney U-test, Chi-square test for comparison of the group parameters and correlation analyses (Spearman analysis) were performed with SPSS statistical software 17.0 (SPSS Inc., Chicago, IL, USA). RESULTS: Type 1 DM group exhibited significantly reduced Schirmer test, increased IOP and decreased retinal thickness relative to the age-matched control group (P < 0.05) but no statistically significant difference was found for the BUT (P = 0.182) and for the CCT (P = 0.495). The correlations between the age, duration, HbA1c and IOP, BUT, Schirmer test, TMV, CRT measurements did not reach statistical significance. CONCLUSIONS: More frequent screening may be needed for complications, including neuropathy-related dry eye syndrome, IOP changes, and diabetic retinopathy in children with Type 1 DM.

The effects of type 1 diabetes mellitus on cardiac functions in children: evaluation by conventional and tissue Doppler echocardiography.

BACKGROUND: Several studies have pointed out the existence of cardiac dysfunction in patients with type 1 diabetes mellitus (DM) even in the absence of ischemic, valvular, or hypertensive heart disease. The present study evaluated cardiac dysfunction and the relationship between severity of disease and degree of cardiac dysfunction in children with type 1 DM. METHODS: In this prospective study, 31 patients with type 1 DM and 33 sex- and age-matched healthy children were evaluated with conventional echocardiography and tissue Doppler echocardiography (TDE). A correlation between cardiac functions and glycated hemoglobin (HbA1C) was examined. RESULTS: TDE results indicated that mitral valve early diastolic annular peak flow rate (E'), mitral valve systolic flow rate (S'), ratio of mitral valve early diastolic peak flow rate to mitral valve early diastolic annular peak flow rate (E/E'), and left ventricular (LV) myocardial performance index (MPI) were higher, and LV ejection time (ET) was shorter in patients with type 1 DM (p<0.05). In addition, tricuspid valve E' and right ventricular (RV) MPI were higher, while RV ET and tricuspid E/E' were lower in patients with type 1 DM compared to healthy children (p<0.05). CONCLUSIONS: Although conventional echocardiography revealed no difference between patients with type 1 DM and healthy children, TDE showed dysfunctions of both ventricles. This state is closely related to degree of blood glucose level control. These findings signify diagnostic value of TDE in the early detection of cardiac effects among patients with type 1 DM.

The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty.

Exposure to environmental chemicals can affect genetic and epigenetic molecular pathways and may cause altered growth and development. Among those exposures, endocrine-disrupting chemicals (EDCs) are of particular concern as humans are abundantly exposed to these chemicals by various means in every period of life. Several well-known environmental chemicals, including phthalates and bisphenol A (BPA), are classified as EDCs. These EDCs are suggested to play roles in early onset of puberty in girls. The aim of this study is to determine plasma phthalate (di(2-ethylhexyl)phthalate [DEHP] and its main metabolite mono(2-ethylhexyl)phthalate [MEHP]) and urinary BPA levels in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). This study was performed on newly diagnosed idiopathic central precocious puberty (CPP) patients (n = 42) and peripheral precocious puberty (PPP) (n = 42) patients, who were admitted to Keçiören Training and Research Hospital, Clinic of Pediatric Endocrinology between August 2012 and -July 2013. Nonobese healthy girls (n = 50) were used as the control group. Urinary BPA levels were not statistically different in control, PPP and CPP groups (medians 10.91, 10.63 and 10.15 µg/g creatinine, respectively; p > 0.05). Plasma DEHP levels were significantly higher in PPP group when compared to control. Plasma MEHP levels were not significantly different in control and PPP groups (p > 0.05). However, in CPP group, both plasma DEHP and MEHP levels were significantly higher than control and PPP groups. This study showed that phthalates might play a role in the occurence of CPP in girls.

Cushing's syndrome: hidden risk in usage of topical corticosteroids.

Iatrogenic Cushing's syndrome in children may occur as a result of the application of exogenous steroids. Prolonged use of powerful corticosteroids suppresses adrenal functions and iatrogenic Cushing's syndrome may develop particularly in infants who are given topical corticosteroids. We report here a case on three infants having Cushing's syndrome with similar clinical presentations due to overuse of topical steroids for diaper dermatitis. The importance of exercising caution during the use of topical steroids is underlined in this study.