Volume 35, Issue 7

Objectives The goal of this study was to determine the quality of these disinfectants’ effects on thyroid function and neurological scores in premature newborns aged 28 to 36 gestational weeks (GW). Methods This cohort study was conducted from October 2020 to September 2021 among 28–36 GW preterm infants at the neonatal care unit of Jiangnan University Hospital. We divided this 12 month period into two consecutive 6 month periods. Composite iodine disinfectants and alcohol are used for skin and umbilical cord disinfection of preterm infants, respectively. Urinary iodine concentration (UIC), thyroid hormone levels, and neonatal behavioral and neurological assessment (NBNA) scores were determined in both groups. Results A total of 126 patients were included in the study, 65 in the iodine exposed group and 61 in the alcohol group. The second UIC and the incidence of serum T4≤5 μg/dL and TSH≥10 mIU/L in the iodine exposed group were significantly higher than those in the alcohol group (p<0.05). The first NBNA score was lower in the iodine exposed group than in the alcohol group (p<0.05). However, whether it has clinical significance remains to be explored. There was a linear relationship between the two NBNA scores (iodine exposure group, R 2 =0.344; alcohol group, R 2 =0.227). No sepsis or other adverse outcomes occurred in the two groups of preterm infants after disinfection with different disinfectants. Conclusions Iodine-containing disinfectants seem to have the potential to cause an increased rate of thyroid dysfunction and a decreased neurological score and should be evaluated in further studies.

Objectives The global spread of coronavirus disease 2019 (COVID-19), had a great impact on patients worldwide, including those with chronic diseases. We aim to study the effect of COVID-19 pandemic on presentation patterns of patients with type 1 diabetes (T1D) in Jordan, as an example a developing country with limited resources. Methods Medical charts were reviewed for patients presented with new-onset T1D to Jordan University hospital during the first year of pandemic and the preceding year. Categorical data were compared using Pearson Chi-Square and Fisher’s exact test. Continuous data were compared using the Independent Sample t-Test. Results A total of 137 children were diagnosed with T1D during the study period, with 60.6% of those children were diagnosed in the pre-pandemic year compared to 39.4% during the first year of pandemic, p-value=0.013. Percentage of patients diagnosed with DKA as first presentation of T1D during the pre-pandemic year was 34.9% compared to 51.9% during the pandemic year, p-value=0.049. Significant differences in family monthly income (p-value=0.006) and paternal education level (p-value=0.036) were found between children with DKA and those without DKA in the pre-pandemic year, but they were not significant during the pandemic year. Conclusions The unprecedented COVID-19 pandemic had affected presentation pattern of newly diagnosed T1D patients, manifested by lower number of children diagnosed with T1D and higher percentage of DKA as first presentation compared to the preceding year. Health care services should be at utmost preparedness for possible future waves and other pandemics.

Objectives Lockdown during the SARS-CoV-2 pandemic generated uncertainty regarding its effects on the control of type 1 diabetes (DM1). Our study aims to evaluate the influence of the pandemic on the control of paediatric patients with DM1. Methods Longitudinal, retrospective, observational study in patients with DM1 attended between 15/10/2019 and 15/03/2020. Data were collected at that visit and at the three subsequent visits. The second was remote in 50% of cases. The variables analysed were: type of insulin therapy, time in range (TIR), time in hypoglycaemia (THypo), time in hyperglycaemia (THyper), coefficient of variation (CV), glycosylated haemoglobin, insulin requirements and anthropometric data. Results 157 patients were recruited. At the post-lockdown visit, the TIR increased and the THyper decreased with respect to the first (p<0.00) and second (p<0.00) visits. Patients treated with subcutaneous infusion showed a higher TIR at the third visit (p=0.03) and lower insulin requirements at the fourth visit (p=0.03) compared to patients treated with multiple doses. Patients with a remote visit presented a higher TIR (p<0.00), a lower THyper (p=0.00) and lower insulin requirements (p=0.01) at the next visit. Patients aged less than 6 years presented a lower glycosylated haemoglobin (p=0.01) and insulin requirements at the third (p=0.03) and fourth (p=0.01) visits, and a lower increase in body mass index (p=0.03) over the year. Conclusions Metabolic control improved at the post-lockdown visit. Patients treated with subcutaneous infusion, those who had a remote visit during strict lockdown and those aged less than 6 years had a better evolution.

Objectives The golden standard test for diagnosing central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test, which has many limitations. This study aimed to investigate the value of insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and basal luteinizing hormone (LH) levels in diagnosing CPP. Methods Cross-sectional study of the levels of IGF-1, IGFBP-3, and basal LH in girls with a chief complaint of premature breast development. Seventy-nine girls with CPP and 37 girls with premature thelarche (PT) diagnosed at West China Second University Hospital from January 2016 to October 2018 were recruited. All patients underwent physical examination, laboratory tests, uterine and ovarian ultrasound, and bone age tests, only CPP patients underwent pituitary magnetic resonance imaging (MRI). Statistical analysis was performed using the SPSS software 21.0. A receiver operating characteristic curve was used to determine diagnostic value. Results The anthropometric data and hormone indicators between CPP and PT were statistically different (p<0.001), except for peak follicle stimulating hormone (FSH) levels (p=0.181). IGF-1, IGFBP-3, and basal LH levels were significantly higher in the subjects with CPP than in those with PT; IGF-1 and basal LH were positively correlated with peak LH and LH/FSH (peak) (p<0.001). The area under the curve (AUC) of IGF-1, IGFBP-3, and basal LH were 0.880, 0.853, and 0.915, respectively. When combined, the AUC reached the highest value of 0.978. Conclusions IGF-1, IGFBP-3, and baseline LH levels were useful in diagnosing CPP. The combined analysis improved the diagnostic effectiveness.

Objectives There are different approaches to diagnosing of the metabolic syndrome (MetS) in adolescents. We aim to compare the proportions of adolescents with abnormal values of MetS components between the NCEP/ATP criteria and the proposed cut-off values from the local population percentile distribution adjusted to gender. Methods Subjects were 358 high school students (246 girls, 112 boys) aged 14–17 years from three Croatian regions. The serum glucose levels were determined by hexokinase method, serum triglycerides by GPO-PAP method, and serum high-density lipoprotein-cholesterol by automated homogeneous assays on Beckman Coulter AU 680 analyser (Minneapolis, USA). Results Differences were seen between genders by NCEP/ATPIII modified criteria in the proportion of the adolescents with the proposed cut-off values for HDL-C levels, SBP, and DBP with a higher prevalence in boys. The proportion of girls differs between data set percentile criteria, and NCEP/ATP III modified criteria for HDL-C value, serum fasting glucose value and DBP value. The proportion of boys with higher values than suggested differs between proposed NCEP/ATP III modified criteria and percentile criteria for serum fasting glucose values and DBP. Conclusions Our study has shown differences in the proportion of 14–17-year-old adolescents between gender according to modified NCEP/ATPIII criteria for HDL-C, SBP and DBP with a higher prevalence of SBP and DBP related to other individual MetS components for both genders. Gender adjusted cut-off value from own populations avoids possible under- or over-estimation in the distribution of individual MetS components with no difference in the proportion of adolescents between gender.

Objectives Childhood obesity and associated comorbidities, including insulin resistance, are increasing in the United States. Our objectives were to (1) determine the prevalence of insulin resistance in children seen in dyslipidemia clinic and (2) evaluate which aspects of the lipid profile correlate with insulin resistance. Methods Children and adolescents seen in a specialized pediatric dyslipidemia clinic without secondary diagnoses known to alter the lipid panel were included. Simultaneous fasting lipid panel, insulin, and glucose levels were available in 572 children (50.5% male). Results Mean patient age was 15.0 ± 3.6 years with the majority being over 10 years of age (92.5%). Mean BMI was 29.8 ± 8.1 kg/m 2 and BMI standard deviation score was 1.80 ± 0.9. Mean HOMA-IR was 6.2 ± 5.7 with a range of 0.4–49.3, and interquartile range of 2.7–7.6. Triglyceride level had a positive correlation with HOMA-IR (p<0.001). HDL-C negatively correlated with HOMA-IR even controlling for triglyceride level by multivariate analysis (p=0.001) and HDL-C <30 mg/dL predicted IR with 41.5% PPV. Conclusions In children and adolescents with dyslipidemia, insulin resistance is common and significantly correlates with reduced HDL-C levels. Non-fasting samples are easier to obtain in children and low HDL-C, which is minimally affected on non-fasting samples, could be an easily obtained indicator of IR. Increasing detection of insulin resistance in children with dyslipidemia may provide greater opportunities for lifestyle interventions and possible pharmacotherapy to modify cardiovascular risk.

Objectives Owing to increase in referrals for precocity observed during COVID-19 lockdown, this study was conducted to estimate the proportion of patients referred for precocity and within these, those with idiopathic central precocious puberty (iCPP) before vs. during the COVID lockdown, and to assess the differences in anthropometric and clinical characteristics among iCPP patients in the two groups. Methods Retrospective study conducted at a tertiary level paediatric endocrinology centre (Western India) evaluating proportion of referrals for precocity and comparing demographics, anthropometry, pubertal staging and bone age at presentation among children with iCPP divided into two groups (pre-lockdown-group 1, lockdown-group 2). Results During lockdown, 155 (5.1%; 146 girls) of 3,053 referrals for precocity as opposed to 59 (1.4%; 54 girls) of 4,208 before the lockdown (p<0.05) were seen; increase was higher in girls (p<0.05). Proportion of referrals for iCPP was significantly higher in the lockdown (4.4%; 136 children vs. 1%; 44 children in group 2) among both genders. Mean age at first visit was 7.8 ± 1.3 and 8.2 ± 1.2 years in groups 1 and 2, respectively. Mean height, weight, BMI and height minus mid-parental height Z scores were not significantly different between the groups. Children in group 2 had a significantly advanced mean bone age (10.7 ± 2 years) and difference in bone and chronological ages (2.5 ± 1.2 years) as compared to group-1 (9.7 ± 1.9; 1.9 ± 1.2) and a larger proportion presented in late puberty. Conclusions We found an increase in the referrals for precocious puberty and an increase in number of children diagnosed with iCPP during COVID lockdown.

Objectives The purpose of this study was to observe the relationship between metabolic syndrome (MetS) and height (Ht) adjusted Z-scores for areal bone mineral density (aBMD) in adolescents. Methods A retrospective study was conducted on the United States adolescents aged 12–17 years. Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2012, 2013–2014 and 2015–2016 cycles. Ht adjusted Z-scores for aBMD were calculated. Results A total of 969 adolescents (493 boys and 476 girls), aged 14.5 ± 1.7 years were enrolled in this study. After control for age, gender, race, 25-hydroxyvitamin D [25(OH)D], and lean body mass index (LBMI) Z-score, adolescents with MetS had significantly lower levels of total body (less head) aBMD Ht-Z-adjusted Z-score than adolescents with one, two components of MetS and without component of MetS (p<0.05) and significantly lower levels of lumbar spine aBMD Ht-Z-adjusted Z-score than adolescents with one component of MetS and without component of MetS (p<0.05). There were significantly negative associations between total body (less head) aBMD Ht-Z-adjusted Z-score and waist circumference (WC) (β=−0.027, p<0.001, R 2 =0.057) and homeostasis model assessment insulin resistance (HOMA-IR) (β=−0.225, p<0.001, R 2 =0.016). There were significantly negative associations between lumbar spine aBMD Ht-Z-adjusted Z-score and WC (β=−0.039, p<0.001, R 2 =0.058) and HOMA-IR (β=−0.251, p<0.001, R 2 =0.008). Conclusions The present study demonstrates that MetS may have a negative effect on bone mineral density in adolescents. Abdominal obesity and insulin resistance play a major role on the decline of aBMD in adolescents.

Objectives Alkaptonuria is a rare autosomal recessive genetic disorder resulting from the deficiency of homogentisate 1,2 dioxygenase (HGD), the third enzyme in the tyrosine degradation pathway. Homogentisic acid produced in excess oxidizes into ochronotic pigment polymer. Accumulation of this pigment in various tissues leads to systemic disease. Methods Clinical, laboratory, molecular findings and treatment characteristics of 35 patients followed up in Ege University Pediatric Nutrition, and Metabolism Department with the diagnosis of alkaptonuria were evaluated retrospectively. Results Twenty-four males (68.57%) and 11 females (31.42%) with a confirmed diagnosis of alkaptonuria from 32 different families were included in the study. We identified 11 different genetic variants; six of these were novel. c.1033C>T, c.676G>A, c.664G>A, c.731_734del, c.1009G>T, c.859_862delins ATAC were not previously reported in the literature. 24 (68.57%) patients only adhered to a low-protein diet in our study group. Seven (20%) patients initiated a low protein diet and NTBC therapy. Mean urinary HGA decreased by 88.7% with nitisinone. No statistical changes were detected in urinary HGA excretion with the low protein diet group. Conclusions In our study, alkaptonuria patients were diagnosed at different ages, from infancy to adulthood, and progressed with other systemic involvement in the follow-up. Since the initial period is asymptomatic, giving potentially effective treatment from an early age is under discussion. Raising disease awareness is very important in reducing disease mortality and morbidity rates.

Objectives Gynecomastia may be due to aromatase excess in several diseases such as obesity and cancer. Aromatase excess syndrome (AEXS) is an autosomal dominant disorder caused by overexpression of CYP19A1 . Germinal mutations occurring in AEXS include various genomic rearrangements including duplication, deletion, and inversion identified in the upstream region of CYP19A1 . Aromatase overexpression caused by a CYP19A1 somatic mutation has been rarely described. Methods Breast adipose tissue biopsies or surgical specimens were obtained from 19 subjects with gynecomastia. Aromatase quantification was performed by digital PCR and CYP19A1 sequencing by RACE PCR products. Results We observed localized aromatase overexpression (>10 fold greater than normal) in breast adipose tissue from three prepubertal males with gynecomastia out of the 19 cases. One carried a chromosomal rearrangement between CYP19A1 and DMXL2 , consistent with AEXS. In the 2 others, the first exon of CYP19A1 contained 11 different tissue-specific promoter subtypes, specifically I.4 or I.3 normally expressed by adipose tissue, but also the placental I.2 promoter and the more ubiquitous I.7 which is usually expressed in breast cancer, uterine, and endothelial tissues. No differences in clinical or biochemical characteristics were observed between these 3 subjects and 16 others without aromatase overexpression. Conclusions We describe two cases of aromatase overexpression in breast adipose tissue associated with nonspecific promoter recruitment. Further investigations are necessary to understand the mechanisms involved in aberrant promoter selection.

Objectives Phthalate is one of the endocrine-disrupting chemicals found in many daily consumer products. Chronic exposure to phthalate may associate with obesity and metabolic abnormalities. However, there is limited information showing a direct relationship between phthalate and body compositions. The aim of the study was to determine the association between urinary phthalate concentration and body composition measure among Thai children. Methods A cross-sectional analytic study on urinary phthalate concentrations and body composition in elementary school children, aged 6–13 years in Bangkok, was conducted during October 2019 to 2020. Urinary phthalate metabolites; (mono-methyl phthalate-MMP, mono-ethyl phthalate- MEP, mono-buthyl phthalate-MBP, and mono-ethylhexyl phthalate-MEHP), in early morning spot urine samples were measured by liquid chromatography tandem mass spectrometry (LC-MSMS) with a quantitation limit of 1 ng/mL. Phthalate exposures were identified through questionnaires. Body composition was measured by Tanita BC-418 ® . Multivariate logistic regression analysis was performed to determine significant associations. Results A total of 364 children were enrolled in the study (boy 51.4%). After adjusting for confounders (sex, caregiver educations, family income, BMI-SDS: Body mass index-standard deviation score, TV watching, and exercise frequency), total urinary phthalate concentrations were associated with fat mass 8.24 (0.94, 15.53), trunk percent fat 7.69 (3.26, 12.12), arm percent fat 3.69 (0.47, 6.91), arm fat mass 72.88 (1.08, 144.67), and leg fat mass 17.79 (2.37, 33.22). Conclusions Higher urinary phthalate concentrations were significantly associated with elevated total fat mass among Thai school-aged children. These findings were not mediated through the degree of obesity defined by BMI. These finding emphasized to be careful when being use phthalate-containing products.

Objectives Delayed puberty is a common presentation to endocrine clinics, with adult height, sexual capability and fertility being the main concerns for the child and his/her family. Presentation is variable including short stature and/or absence of secondary sexual characteristics. The aetiology can either be constitutional, functional or permanent hypogonadotropic hypogonadism, permanent hypergonadotropic hypogonadism or unclassified. Despite the importance of this subject, there are no publications from Sudan. Methods A retrospective hospital-based study. Records of all patients who were seen in the endocrinology unit at Gaffar Ibn Auf Children’s Hospital and were diagnosed as having delayed puberty were reviewed and demographic, clinical, and investigations data were obtained. Results A total of 136 patients were included in this study. Presentation includes short stature in 52.2%, both short stature and delayed puberty in 27.2%, and delayed puberty in 20.6%. The most common aetiologies were permanent hypogonadotropic hypogonadism and functional hypogonadotropic hypogonadism presented in 37.5% and 36% respectively, while constitutional delay of growth and puberty was found in only 14.7%. Type 1 diabetes mellitus (T1DM) was the most frequent chronic illness followed by coeliac disease. Hypergonadotropic hypogonadism was diagnosed in 11.7%, the majority of which were females. Conclusions The aetiological pattern reported in this series highlights the role of nutrition and general well-being in pubertal development, as well as the major impact of genetics and consanguinity on disease patterns. Data from African countries are limited and this is the first reported cohort on delayed puberty from Sudan.

Objectives Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare autosomal recessive disorders characterized by near/total absence of body fat. Pathogenic variants in polymerase-I and transcript release factor gene (PTRF), or CAVIN1, is responsible for CGL4. In addition to generalized fat loss, patients with CGL4 were reported to suffer from myopathy, malignant cardiac arrhythmias, gastrointestinal disorders, and skeletal abnormalities. Here we describe the phenotype of a child with CGL4 due to a rare, novel pathogenic variant in the PTRF/CAVIN1 gene and the long-term effects of metreleptin substitution on comorbidities. Case presentation We describe a now 20-year-old female patient. At the age of 14-years, she was referred to the University Clinic because of uncontrolled diabetes with an HbA1c of 9.3%, requiring 2.4 IU insulin/kg total-body-weight to normalize blood glucose, hepatomegaly, and hypertriglyceridemia of 515 mg/dL. Additionally, she was suffering from malignant cardiac arrhythmia, myopathy, and hyperCKemia. In light of these clinical findings, she was diagnosed with CGL due to a rare, novel variant in the PTRF gene, and was started on metreleptin, a synthetic analog of human leptin. After the initiation of metreleptin treatment, insulin therapy could be stopped and improvement of sonographically assessed liver size was observed, even though serum liver function test stayed mildly elevated. Furthermore, a noticeable improvement of the serum triglyceride levels was also seen. Medical care and regular follow-up visits are being carried out by a multi-disciplinary team. Conclusions Although CGL4 is rare, due to its life-threatening comorbidities and the opportunity for an early intervention, it is important that the clinicians should recognise these patients.

Objectives 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) deficiency results in insufficient biosynthesis of testosterone and consequently dihydrotestosterone. This is important for the fetal development of male genitalia. Thus, most 46,XY patients with 17β-HSD3 deficiency have a female appearance at birth and present with virilization at puberty. This study presents the differences in the clinical and hormonal data and analyses of gonadal characteristics in two siblings with 17β-HSD3 deficiency. Case presentation Patient 1 presented with deepening of the voice and signs of virilization at puberty and increased serum levels of testosterone (T) of 10.9 nmol/L (2.9 SDS) and androstenedione (Δ4) of 27 nmol/L (3.3 SDS) were observed. The T/Δ4-ratio was 0.39. Patient 2 was clinically prepubertal at the time of diagnosis, but she also had increased levels of T at 1.97 nmol/L (2.9 SDS), Δ4 at 5 nmol/L (3.3 SDS), and the T/Δ4-ratio was 0.40, but without signs of virilization. Both siblings were diagnosed as homozygous for the splice-site mutation c.277+4A>T in intron 3 of HSD17B3 . They were subsequently gonadectomized and treated with hormone replacement therapy. The gonadal histology was overall in accordance with pubertal status, although with a dysgenetic pattern in both patients, including Sertoli-cell-only tubules, few tubules containing germ cells, and presence of microliths. Conclusions Two siblings with 17β-HSD3 deficiency differed in pubertal development at the time of diagnosis and showed marked differences in their clinical presentation, hormonal profile, gonadal morphology and expression of cell lineage markers. Early diagnosis of 17β-HSD3 deficiency appears beneficial to ameliorate long-term consequences.

Objectives X-linked adrenal hypoplasia congenita (AHC) is characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Herein, we report a rare case of X-linked AHC with central precocious puberty (CPP). Case presentation An 11-month-old male patient was found to have premature pubarche, enlargement of the penis, and frequent erection. LH and FSH levels after the GnRHa test were in the pubertal range. Direct sequencing revealed a heterozygous variant of the NR0B1 gene. The proband was treated with hydrocortisone and 9-alpha fludrocortisone because of the significantly elevated ACTH and renin activity. The secondary sexual characteristics relieved gradually. The serum testosterone and LH subsequently returned to the prepubertal range. The basal serum FSH values have been between 1.0 and 2.0 IU/L since the age of 2.25 years, with extremely low AMH levels beginning at 3 years. Conclusions The clinical course of CPP with NR0B1 variant may be temporary. HPG axis status of X-linked AHC may probably be pleomorphic during the longitudinal follow-up.

Objectives Congenital generalized lipodystrophy type 4 (CGL4) is a rare autosomal recessive condition with high rates of morbidity and mortality. It is a multisystem condition associated with ventricular tachyarrhythmia, congenital myopathy, hepatitis, and metabolic profile of severe hypertriglyceridemia and insulin resistance. Metreleptin is the first line treatment, however it is unavailable in several countries. Herein, we describe a unique presentation and treatment of CGL4. Case presentation A 16-year-old female presented with insulin resistant diabetes, and was later found to have myopathy, hypertriglyceridemia, nonalcoholic fatty liver disease, ventricular arrhythmias, and genetic confirmation of CGL4 due to homozygous change in CAVIN1 gene. She had severe hypertriglyceridemia, frequently >17 mmol/L, requiring several hospital admissions. To better control hypertriglyceridemia, in context of known congenital myopathy, we opted for treatment with icosapent ethyl, an ethyl ester of eicosapentaenoic acid (EPA), which reduces synthesis and enhances clearance of triglycerides. On this treatment, she was able to maintain stable triglyceride levels of 4 mmol/L. Conclusions We present the first case report of a patient with CGL4, successfully treated for hypertriglyceridemia, with icosapent ethyl.