Does an episode of diabetic ketoacidosis affect thyroid function tests in pediatric patients?

OBJECTIVES: The aim of our study was to investigate the changes in thyroid hormone levels during and after acute metabolic disorder in patients with diabetic ketoacidosis (DKA). METHODS: Eighty five patients diagnosed with DKA were included in the study. Patients with control thyroid function test (TFT) values at admission (the first blood sample) and 1 month later were included in the study. Thyroid function tests obtained during diabetic ketoacidosis and at the first month follow-up were compared. Euthyroidism and euthyroid sick syndrome were defined and grouped according to current guidelines. The mild and moderate groups, according to DKA classification, were combined and compared with the severe group. RESULTS: A significant increase was observed between the first admission and the control TFT values 1 month later. However, there was no significant difference found in TFT between mild/moderate and severe groups taken at the time of DKA. Difference between two groups, euthyroid sick syndrome and euthyroid, was examined and the result that was different from the literature was the difference between TSH levels. We found that low FT4 levels were associated with higher HgbA1c, although the correlation was weak. CONCLUSIONS: Thyroid hormone levels may not reflect a thyroid disease during severe DKA attack. Therefore, it is unnecessary to check thyroid function tests.

Identification of a novel homozygous NR5A1 variant in a patient with a 46,XY disorders of sex development.

OBJECTIVES: Nuclear receptor subfamily 5 group A member 1 (NR5A1) is a transcription factor critical for the development of various organs. Pathogenic variants in NR5A1 are associated with a spectrum of disorders of sex development (DSD). CASE REPORT: A 15-month-old baby, raised as a girl, was referred for genital swelling and ambiguous genitalia. Born to healthy consanguineous parents, the baby had a phallus, perineal hypospadias, labial fusion, and a hypoplastic scrotum. Hormonal evaluation showed normal levels, and ultrasonography revealed small gonads and absence of Müllerian derivatives. Post-human chorionic gonadotropin (hCG) testing indicated an adequate testosterone response. The karyotype was 46,XY, and in it was found a homozygous NR5A1 variant (c.307 C>T, p.Arg103Trp) in a custom 46 XY DSD gene panel. Notably, the patient exhibited complete sex reversal, hyposplenia, and no adrenal insufficiency. CONCLUSIONS: Previously, NR5A1 pathogenic variants were considered to be dominantly inherited, and homozygous cases were thought to be associated with adrenal insufficiency. Despite the homozygous pathogenic variant, our patient showed hyposplenism with normal adrenal function; this highlights the complexity of NR5A1 genotype-phenotype correlations. These patients should be monitored for adrenal insufficiency and DSD as well as splenic function.

Evaluation of Serum Advanced Glycation End Product Levels and Microvascular Complications in Children and Adolescents with Type 1 Diabetes Mellitus.

OBJECTIVE: Advanced glycation end products (AGEs) are irreversible macromolecules formed by nonenzymatic reactions due to chronic hyperglycemia. The aim of this study was to assess the relationship between AGEs and the microvascular complications of children and adolescents with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: Twenty-six T1DM patients with microvascular complications and 58 complication-naive patients who were similar regarding age, sex, and pubertal status enrolled in the study. Anthropometric, biochemical, ophthalmologic, and neurologic variables were compared with serum AGEs levels by the fluorescence method. RESULTS: There was no significant difference observed between the patients with complications and those without complications in terms of serum levels of AGEs and other biochemical parameters. However, the duration of T1DM and urine microalbumin-creatinine ratio (uACR) were significantly higher in the complication-positive group (P < .001). Serum levels of AGEs were found to be similar when retinopathy, peripheral, and optic neuropathy were separately compared with the complication-naive group (P > .05). However, patients with nephropathy had significantly higher serum levels of AGEs than patients without complications (P = .023). In addition, there was a significant positive correlation between serum AGEs levels and uACR (P = .042) but not other parameters (P > .05). CONCLUSION: This study is the first to evaluate the association between serum AGEs levels and microvascular complications in children and adolescents with T1DM. Our study highlights that serum AGEs levels are significantly correlated with nephropathy but not with retinopathy and neuropathy. Further long-term studies with a larger sample size are required to establish a better relationship between diabetic complications and AGEs. Cite this article as: Kirkgöz T, Acar S, Küme T, et al. Evaluation of serum advanced glycation end product levels and microvascular complications in children and adolescents with type 1 diabetes mellitus. Turk Arch Pediatr. 2024;59(1):31-37.

Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes

ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes.

Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

Hypoparathyroidism in children and adolescents.

Hypoparathyroidism is characterized by insufficient parathyroid hormone (PTH) release from the parathyroid glands to maintain serum calcium level within normal limits and unresponsiveness of target tissues despite normal serum PTH level. Hypoparathyroidism is defined as low or inappropriately normal serum PTH level. In this narrative review, we discuss the etiology of hypoparathyroidism in children.

The Association between Vitamin D deficiency and Hepatosteatosis in Children and Adolescents with Obesity.

INTRODUCTION: Increasingly, research groups have been studying the association of serum vitamin D and metabolic health indicators, especially in patients with obesity. We compared the serum 25-hydroxy Vitamin D [25(OH)D] concentrations in children and adolescents who had obesity and hepatosteatosis with children and adolescents who had obesity without hepatosteatosis, and investigate the relationship between serum 25(OH)D concentrations and severity of hepatosteatosis. We also aimed to assess the effect of vitamin D treatment after 6 months on hepatosteatosis and liver biochemistry. METHODS: One hundred thirty-three patients with obesity (body mass index (BMI) > +2 standard deviations (SD) for their age and gender) and vitamin D deficiency [serum 25(OH)D < 12 ng/ml] were recruited. Anthropometric measurements, biochemical parameters [serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25(OH)D, glucose and insulin concentrations] and ultrasonographic findings of hepatosteatosis were recorded before and six months after Vitamin D treatment. Chi-square, Student's t tests and multivariate analysis were performed. RESULTS: Grade 1, 2 and 3 hepatosteatosis at baseline was present in 51 (38.4%) , 43 (32.3%) and 10 (7.5%) subjects respectively. Mean (± SD) serum 25(OH)D concentrations were significantly lower in those with hepatosteatosis (8.4 ± 2.4 ng/ml) compared with those without hepatosteatosis (9.9 ± 2.4 ng/ml, P < 0.005). Multivariable logistic regression analysis showed serum 25(OH)D concentration was the independent predictor for hepatosteatosis (P < 0.005), whereas age, sex, weight SD, BMI SD and HOMA-IR were not (P > 0.05). There was no significant difference in BMI SD, HOMA-IR and liver enzymes between subjects with and without hepatosteatosis (P > 0.05). Despite improvement in serum 25(OH)D concentrations at 6 months post-treatment (34.7 ± 10.6 ng/ml vs. 8.7 ± 2.4 ng/ml; p < 0.0001), there was no significant difference in the proportion of patients with different severity of hepatosteatosis as compared to before treatment (p = 0.88). CONCLUSION: Serum 25(OH)D concentrations were lower in children and adolescents with obesity and hepatic steatosis as compared to those without hepatic steatosis, with an inverse association between the severity of hepatosteatosis and serum 25(OH)D concentrations. Vitamin D treatment in children and adolescents with obesity and hypovitaminosis D did not improve severity of hepatic steatosis on ultrasonography at 6 months.

Molecular diagnosis in patients with monogenic diabetes mellitus, and detection of a novel candidate gene.

AIM: We aimed to investigate molecular genetic basis of monogenic diabetes (DM) and novel responsible candidate genes with targeted Next Generation Sequencing (NGS) and Whole Exome Sequencing (WES). METHODS: A hundred cases presenting with clinical findings and a family history of monogenic DM were included in the study. Molecular analysis was performed using an NGS panel including 14 genes. Following targeted NGS, WES was planned in cases in whom no variant was detected. RESULTS: Thirty different disease-causing variants in seven different genes were detected in thirty-five (35 %) cases with targeted NGS approach. Most common pathogenic variant was found in GCK gene in 25 (25 %) cases. Four different variants were detected in 4 (4 %) patients in ABCC8 gene. In 45 of 65 cases; WES analyses were done. A heterozygous c.2635C > T(p.Gln879Ter) variant was detected in IFIH1 gene in a patient with incidental hyperglycemia. In the segregation analysis affected mother was shown to be heterozygous for the same variant. CONCLUSION: Molecular etiology was determined in 35 % cases with the NGS targeted panel. Seventeen novel variants in monogenic DM genes have been identified. A candidate gene determined by WES analysis in a case that could not be diagnosed with NGS panel in this study.

The therapeutic effect of oral desmopressin lyophilisate formulation in children with central diabetes insipidus.

OBJECTIVES: We aimed to assess the efficacy of oral use of oral desamino-D-arginine-8-vasopressin lyophilisate (OLD) in children with central diabetes insipidus (CDI). METHODS: Clinical, laboratory, and imaging characteristics of twenty-five children with CDI treated with OLD were evaluated. RESULTS: Fourteen boys and eleven girls with a mean age of 52.37 months were evaluated. These children (mean weight and height at admission, 26.81 ± 14.8 kg vs. 92.52 ± 30 cm) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatremia (mean sodium level, 143.12 ± 8.6 mEq/L). At the time of hypernatremia, mean serum and urine osmolality were 298.2 ± 18 mOsm/kg and 160.20 ± 8.7 mOsm/kg, respectively. ADH levels were undetectable (<0.5 pmol/L) at admission in all cases. Oral administration of desmopressin lyophilisate (120 µg/tablet) was initiated at a dose of 5 µg/kg/day in two divided doses together with controlled water intake to avoid hyponatremia. Serum sodium levels normalised in a mean duration of 15.2 ± 16.4 h with a mean decline rate of 0.12 ± 0.04 mEq/L/h. Nine children needed rehospitalization because of hypernatremia due to non-compliance. Four episode of hyponatremia was observed. Weight gain and growth were normal during the mean follow-up duration of 37.79 ± 48.2 months. CONCLUSIONS: Administration of OLD was practical and safe in the treatment of CDI in children with CNS malformations in this small retrospective series.

Comparison of Optical Coherence Tomography Angiography Findings between Healthy Children and Children with Type 1 Diabetes Mellitus and Autoimmune Thyroiditis

Objective: The aim of this study was to compare the development of early diabetic retinopathy (DR) findings, a microvascular complication, between patients with isolated type 1 diabetes mellitus (T1DM) (Group 1), concurrent T1DM and autoimmune thyroiditis (AT) (Group 2), and healthy controls (Group 3), who were matched for age, sex, number, and body mass index for comparison. Methods: This was a prospective observational study that included individuals aged 10-20 years, and patients in Groups 1 and 2 had been followed up for ≥5 years. None of them developed clinical DR during the follow-up period. Optical coherence tomography angiography (OCTA) was used to evaluate the foveal avascular zone (FAZ) and parafoveal vascular density (PVD) for the development of early DR. OCTA findings were compared between patients and healthy controls. Results: Thirty-five individuals were included in each of the groups. The mean FAZ and PVD differed significantly between the three groups (FAZ, p=0.016; PVD, p=0.006). The mean FAZ was higher in Groups 1 and 2 than in Group 3 (p=0.013 and p=0.119, respectively). The mean PVD was lower in Groups 1 and 2 than in Group 3 (p=0.007, respectively). No significant difference was found between Groups 1 and 2 in terms of the mean FAZ and PVD (p=0.832 and p=0.653, respectively). The mean glycated hemoglobin (HbA1c) level was significantly correlated with FAZ and PVD (FAZ: r=0.496, p<0.001; PVD: r=-0.36, p=0.001). Conclusion: In patients with T1DM who did not develop clinical DR, OCTA findings revealed an increase in FAZ, which was associated with higher HbA1c levels. The mean PVD was significantly lower in the group with coexisting AT and T1DM than in the control group. These results suggest that the coexistence of AT and T1DM can contribute to the development of microvascular complications. However, studies with larger patient series are required.

Management of Central Diabetes Insipidus in Disabled Children with Diluted Oral Desmopressin Lyophilisate Formulation Administered Through Nasogastric Tube: A Retrospective Case Series.

BACKGROUND: Experience with nasogastric administration of oral DDAVP [desamino-D-arginine-8-vasopressin] lyophilisate (ODL) for central diabetes insipidus (CDI) in disabled children with swallowing coordination difficulties is limited. OBJECTIVE: We aimed to assess the safety and efficacy of nasogastric use of ODL in disabled children with CDI. Time to serum sodium normalisation was compared with that of children with normal intellect and CDI treated with sublingual DDAVP. METHODS: Clinical, laboratory and neuroimaging characteristics were evaluated for 12 disabled children with CDI treated with ODL through nasogastric tube at Dr Behcet Uz Children's Hospital, Turkey, between 2012 and 2022. RESULTS: Six boys and six girls with a mean (±SD) age of 43 (± 40) months were evaluated. These children (mean [±SD] weight standard deviation score [SDS] - 1.2 ± 1.7; mean [±SD] height SDS - 1.3 ± 1.4) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatraemia (mean serum sodium 162 [±3.6] mEq/L). At diagnosis, mean serum and urine osmolality were 321 (± 14) mOsm/kg and 105 (± 7.8) mOsm/kg, respectively. Arginine vasopressin (AVP) levels were undetectable (< 0.5 pmol/L) at diagnosis in all patients. Nasogastric tube administration of DDAVP lyophilisate (120 µg/tablet) dissolved in water (10 mL) was commenced at a dose of 1-5 µg/kg/day in two divided doses together with controlled water intake to avoid hyponatraemia. The frequency and dose of DDAVP were titrated based on urine output and serum sodium concentration. Serum sodium declined at a rate of 0.11 ± 0.03 mEq/L/h and reached normal range in a mean duration of 174 ± 46.5 h. Serum sodium declined faster in children with normal intellect and CDI treated with sublingual DDAVP (1.28 ± 0.39 mEq/L/h; p = 0.0003). Three disabled children needed rehospitalisation because of hypernatraemia due to unintentional DDAVP omission by caregivers. No episode of hyponatraemia was observed. Weight gain and growth were normal during the median (± interquartile range) follow-up duration of 32 ± 67 months. CONCLUSIONS: Nasogastric administration of oral DDAVP lyophilised formulation was safe and effective in the treatment of CDI in disabled children in this small retrospective series.

Approach to nutritional rickets.

Rickets is the disease of a growing skeleton and results from impaired apoptosis of hypertrophic chondrocytes and mineralization of the growth plate. Nutritionally induced rickets, secondary to vitamin D and/or calcium deficiency, remains a major global problem. In this review, we discuss pathogenesis, clinical signs, investigation and management of nutritional rickets.

Multidetector Computed Tomographic Evaluation of the Normal Characteristics of the Thymus in the Pediatric Population.

Objectives: The objective of the present study was to determine the morphologic features and measurements of the normal thymus on contrast-enhanced multi-detector computed tomography (MDCT) in subjects from the newborn period up to 18 years of age. Materials and Methods: The MDCT scans obtained from 464 children with a mean age ± SD of 8.43 ± 5.60 years were retrospectively re-evaluated. The shape, margins, side predominance, density, and measurements of the thymic gland were defined for each age group. Results: A triangular thymic shape with a middle location and straight lateral contours were the most frequently seen morphologic features in children. The mean anteroposterior and transverse diameter of the thymus was 17.32 ± 4.58 and 29.99 ± 11.42 mm, respectively. The mean values for the width and thickness were 20.66 ± 5.36 and 15.15 ± 6.76 mm for the right thymic lobe, respectively; and 26.14 ± 7.85 and 14.91 ± 5.51 mm for the left, respectively. The transverse diameter of the thymus and thymic lobe dimensions decreased significantly with age, however, the anteroposterior diameter of the thymus was not significantly associated with age. Girls had higher mean thymic attenuation values compared to boys, however, this gender difference was not statistically significant (63.8 ± 22.4 HU vs. 60.1 ± 25.3, p = 0.164). Conclusion: Our study provides a better understanding of the normal thymic appearances in children that can aid in accurate diagnosis and avoid unnecessary, costly, and invasive interventions.

Clinical and Genetic Characteristics of Patients with Common and Rare Types of Congenital Adrenal Hyperplasia: Novel Variants in STAR and CYP17A1.

Objectives: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases characterized by salt wasting or virilization. 21 hydroxylase deficiency (21-OHD) accounts for 90-95% of all cases of CAH and caused by the genetic defects of CYP21A2. Other forms include 3-ß-hydroxysteroid dehydrogenase deficiency, 11-ß-hydroxylase deficiency (11ß-OHD) (%5-8), 17-α-hydroxylase deficiency (17α-OHD), and steroidogenic acute regulatory protein (STAR) defects (congenital lipoid adrenal hyperplasia) with mutations in HSD3B2, CYP11B1, CYP17A1, and STAR, respectively. Objectives: Herein, we aimed to present the clinical and genetic features of 64 patients with various types of CAH. Methods: Sixty-four patients with CAH, monitored in the Izmir Dr. Behcet Uz Children Hospital Division of Pediatric Endocrinology, were retrospectively analyzed for the clinical, laboratory, and genetic data. Results: Fifty-six patients (87.5%) had 21-OHD and four patients (6.3%) had 17α-OHD, three patients (4.7%) had 11ß-OHD, and one patient (1.5%) had STAR defect. The most common presenting features in 21-OHD were ambiguous genitalia. Patients with 21-OHD were diagnosed earlier than the rare groups. Disease-causing variants of CYP21A2 were identified in 46 patients. The most common mutations were IVS2, Q318X, I172N, and large deletions. Three patients with 11ß-OHD were presented with enlargement of penis and early pubic hair at the median presenting age of 26 months. 17α-OHD deficiency was detected in 4 cases. Genetic analysis revealed two different homozygous CYP17A1 variants. The patient with STAR defect was presented with dehydration and cholestasis in 44 days of the life. Genetic analysis of patient with STAR deficiency revealed a novel homozygous variant. Conclusion: The current study reported a genotype-phenotype correlation consistent with literature data in CAH cases with 21-OHD. This study also reported novel homozygous variants in STAR and CYP17A1 genes that lead to rare types of CAH.

Impact of the coronavirus disease 2019 pandemic on obesity, internet addiction, and sleep quality in adolescents.

PURPOSE: This descriptive cross-sectional study aimed to examine the effects of the coronavirus disease-19 (COVID-19) pandemic on obesity, Internet addiction, and sleep quality in adolescents. METHODS: In this study, data were collected from 395 healthy adolescents using a sociodemographic form, an Internet addiction scale, and a sleep quality scale. Descriptive statistics were analyzed as numbers, percentages, and mean values. The Wilcoxon test was performed to compare the mean body mass index (BMI), Internet addiction, and sleep quality scores of the participants before and after the COVID-19 pandemic. The differences were significant at a p value of <0.05. RESULTS: The mean age of the participants was 15.04 ± 1.81 years, and 53% of them were female. The difference between the mean BMI scores of adolescents before and after the COVID-19 pandemic was significant (p < 0.01). The difference between the mean Internet addiction scale scores of the participants before and after the COVID-19 pandemic was significant (p < 0.01). The difference between the mean sleep quality scale scores before and after the COVID-19 pandemic was also significant (p < 0.01). Approximately 27.1% and 34.9% of the participants were obese before and after COVID-19, respectively. CONCLUSION: The obesity rate, BMI, and Internet addiction levels of children increased, whereas their sleep quality decreased after the COVID-19 pandemic. PRACTICAL IMPLICATIONS: During the pandemic period, online trainings for parents should be organized on planning physical activities during closure periods, regulating the adolescents' sleep and eating habits.

A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis.

Dysosteosclerosis (DOS) is a rare sclerosing bone dysplasia characterized by unique osteosclerosis of the long tubular bones and platyspondyly. DOS is inherited in an autosomal recessive manner and is genetically and clinically heterogeneous. To date, four individuals with DOS who have five different TNFRSF11A mutations have been reported. Based on their data, it is hypothesized that mutations producing aberrant mutant RANK proteins (missense or truncated or elongated) cause DOS, while null mutations lead to osteopetrosis, autosomal recessive 7 (OPTB7). Herein, we present the fifth case of TNFRSF11A-associated DOS with a novel homozygous frame-shift mutation (c.19_31del; p.[Arg7CysfsTer172]). The mutation is predicted to cause nonsense mutation-mediated mRNA decay (NMD) in all RANK isoform transcripts, resulting in totally null allele. Our findings suggest genotype-phenotype relationship in TNFRSF11A-associated OPTB7 and DOS remains unclear, and that the deficiency of TNFRSF11A functions might cause DOS, rather than osteopetrosis. More data are necessary to understand the phenotypic spectrum caused by TNFRSF11A mutations.

Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing.

OBJECTIVES: Non-syndromic monogenic obesity is a rare cause of early-onset severe obesity in the childhood period. The aim of this study was to screen four obesity related genes (LEP, LEPR, MC4R and POMC) in children and adolescents who had severe, non-syndromic early onset obesity. METHODS: Next-generation sequencing of all exons in LEP, LEPR, MC4R and POMC was performed in 154 children and adolescents with early onset severe obesity obesity. RESULTS: Fifteen different variants in nineteen patients were identified with a variant detection rate of 12.3%. While six different heterozygous variants were observed in MC4R gene (10/154 patients; 6.5%), five different variants in POMC gene (four of them were heterozygous and one of them was homozygous) (6/154 patients; 3.9%) and four different homozygous variants in LEPR gene (3/154 patients; 1.9%) were described. However, no variants were detected in the LEP gene. The most common pathogenic variant was c.496G>A in MC4R gene, which was detected in four unrelated patients. Six novel variants (6/15 variants; 40%) were described in seven patients. Four of them including c.233C>A and c.752T>C in MC4R gene and c.761dup and c.1221dup in LEPR gene were evaluated as pathogenic or likely pathogenic. CONCLUSIONS: In conclusion, MC4R variants are the most common genetic cause of monogenic early-onset obesity, consistent with the literature. The c.496G>A variant in MC4R gene is highly prevalent in early-onset obese patients.

Impact of Obesity on Bone Metabolism in Children.

Obesity is an epidemic disease that can increase the incidence of type 2 diabetes, cardiovascular disease, malignancy, hypertension, and other health problems that affect the musculoskeletal system. There is a complex interaction between obesity and bone metabolism. In children with obesity, the peroxisome proliferator-activated receptor gamma pathway causes the differentiation of mesenchymal stem cells into adipocytes via osteoblasts, in which results in low bone mass and osteoporosis. Systemic inflammation in obesity has negative effects on bone metabolism. An increase in the number and size of adipose tissue and adipocytokines secreted from adipocytes affect the bone mass of the whole body with hormonal and biochemical effects. The skeletal effects of obesity are mediated by higher oxidative stress and increased production of proinflammatory cytokines. Osteoporosis due to obesity has increased morbidity and mortality in recent years, resulting in important health problems in developed and developing countries.

Sonographic evaluation of normal thyroid volume and thyroid isthmus depth among infants in the west coast of Turkey.

INTRODUCTION: The reference values for thyroid volume (TV) suggested by the WHO are recommended for children aged 6 to 12 years and cannot be considered relevant for infants. The present study aimed to establish the normal values for TV and thyroid isthmus depth (TID) in infants aged between 1 and 12 months from the west coast of Turkey. MATERIAL AND METHODS: The TV and TID were measured in 223 infants by a validated ultrasound technique. The TV was determined by the method of Brunn et al. and Brown et al. The 3rd, 25th, 50th, 75th, and 97th percentiles of the TV and TID according to age were produced. The TV and TID measurements were compared with infants' age, gender, and standard deviation (Z) scores for weight, height, and BMI. RESULTS: The median (IQR) values for TV were 0.77 (0.61-1.00) and 0.84 (0.67-1.10) mL, calculated according to the formula of Brunn et al. and Brown et al., respectively. The TV was significantly associated with age, and Z scores for weight, height, and body mass index (BMI) (r = 0.366, p < 0.001; r = 0.343, p < 0.0001; r = 0.269, p < 0.0001; and r = 0.157, p = 0.019; respectively). The median (IQR) value for the TID was 1.5 (1.3-1.9) mm. The TID was significantly correlated with TV and the Z score for height (r = 0.190, p = 0.004; and r = 0.144, p = 0.032; respectively). In multivariable regression, the only independent predictor for TV was the Z score for BMI. No differences based on gender were found. CONCLUSIONS: This is the first study to report the normative values for TV and TID in healthy Turkish infants aged up to 12 months. Our findings may serve as a basis for developing national and international references for TV and TID in infants.

How Vitamin D Levels of Children Changed During COVID-19 Pandemic: A Comparison of Pre-pandemic and Pandemic Periods

Objective: The synthesis of vitamin D is related to sun exposure, thus the restrictions during the Coronavirus disease-2019 (COVID-19) pandemic may have affected the levels of vitamin D in all age groups. The aim of this study was to evaluate vitamin D levels of healthy children and adolescents during the first year of the pandemic. Methods: The study group included healthy children and adolescents who were admitted for general check-ups and evaluated with 25(OH)D levels. Then, it was divided into two groups: Group 1 "pre-pandemic", and Group 2 "pandemic". Vitamin D levels were recorded from the hospital database and were compared according to age groups, gender, and the season, retrospectively. Results: The study group [mean age=90.29±59.45 median age=79 interquartile range (IQR): 102 months, male/female: 1409/1624] included 3033 children and adolescents (Group 1/Group 2 n=1864/1169). Although the mean 25(OH)D levels among preschool children did not differ between groups, the vitamin D levels of school-aged children and adolescents were significantly lower in the pandemic period than in the pre-pandemic period [Group 1 median=16.50 (IQR: 10.5) vs Group 2 median=15.9 (IQR: 11.3) in 6-12 age group (p=0.026); Group 1 median=13.30 (IQR: 10.2) vs Group 2 median=11.20 (IQR: 9.7) in 12-18 age group (p=0.003)]. Moreover, the 25(OH)D levels of adolescents showed seasonal variance with lower levels in winter, and unexpectedly, in summer. Conclusion: Pandemic-related restrictions have caused significant decreases in vitamin D levels of school-aged children and adolescents. We suggest that children and adolescents should be given vitamin D supplementation in order to maintain sufficient levels of vitamin D during the pandemic.