Volume 37, Issue 9

Objectives We sought to determine if the early months of the coronavirus disease 2019 (COVID-19) pandemic influenced pediatric diabetic ketoacidosis (DKA) hospitalization characteristics. Methods This is a cross-sectional study of youth with laboratory-confirmed DKA admitted to a large tertiary children’s hospital in the USA. Data were collected from admissions in March through July 2019 and March through July 2020, respectively. We evaluated the clinical characteristics of hospitalization, including demographic data and DKA severity. We used univariable ordinal logistic regression followed by multiple ordinal logistic regression to adjust for potential confounders. Results We included 137 children with diabetes admitted for DKA in the relevant period in 2019 and 173 patients admitted for DKA in the same period in 2020. Hemoglobin A1C (HbA 1c ) upon admission was higher in 2020 (median=12.2 %) than in 2019 (11.5 %, p=0.018). Children who were admitted with DKA in 2020 were less likely to be autoantibody positive than those in 2019 (83 vs. 91 %, p=0.028). In the univariable model, being admitted in 2020 was significantly associated with more severe DKA (p=0.038), as was HbA 1c (p=0.001). After adjusting for HbA 1c upon admission, admission year was no longer significantly associated with more severe DKA. Conclusions In this study of pediatric diabetes of any type and duration of diabetes, youth admitted for DKA at the start of the COVID-19 pandemic, compared with those admitted during the year before, were more likely to have autoantibody-negative diabetes and had significantly higher HbA 1c . Additionally, higher HbA 1c seemed to mediate more severe DKA during the pandemic.

Objectives To study the urinary neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (β2M) levels as markers of tubular damage in children with type 1 diabetes (T1DM). Methods Forty T1DM children and 40 age-matched controls were enrolled. Subjects with coexisting kidney disorder, intake of oral glucose lowering drugs and syndromic diabetes mellitus were excluded. Fasting plasma glucose, glycated hemoglobin (HbA 1c ), kidney function, urinary albumin-creatinine ratio (UACR), NGAL and β2M were measured and compared in cases and controls. Results The median (IQR) age of cases and controls was 10.6 (8, 14.2) and 10.7 (8.4, 13.7) years, respectively. Cases had disease duration of 4 (3, 6.8) years and HbA 1c 10.9 (9, 13.1) %. Microalbuminuria was seen in 14 (35 %). Median (IQR) levels of UACR were higher in cases than controls [19.38 (10.27, 35.26) and 6.49 (3.10, 11.65) µg/mg; p<0.001], similarly NGAL/creatinine [352.21 (191.49, 572.45) and 190.54 (125.91, 322.83) ng/mg; p=0.006], unlike β2M/creatinine [1.7 (0.43, 6.02) and 2.12 (1.05, 4.47) µg/mg; p=0.637]. Children with higher HbA 1c (≥10 %) had higher urinary ACR and tubular biomarkers than HbA 1c <10 % (p>0.05). Urinary ACR showed positive correlation with NGAL/creatinine (r=0.38, p=0.019) and β2M/creatinine (r=0.42, p=0.009). Conclusions Urinary biomarkers NGAL and β2M were elevated in the presence of normal urinary microalbumin levels suggestive of early tubular damage in T1DM.

Objectives Gonadotropin-releasing hormone (GnRH) test is the gold standard test to evaluate the hypothalamus–pituitary–gonadal (HPG) axis for the diagnosis of central precocious puberty (CPP). However, the diagnosis of cases with clinical features of CPP whilst have borderline peak luteinizing hormone (LH) remain challenges. We aimed to evaluate diagnostic performance of the average of LH levels measured during GnRH stimulation test. Methods Cases with diagnosis of CPP and premature thelarche (PT) who had a GnRH stimulation test results were retrospectively reviewed. Anthropometric measurements (weight, height, and body mass index), age and sex-specific standard deviation scores, growth velocity, puberty stages, bone ages, serum FSH, LH, and estradiol levels were measured by electrochemiluminescence immunological method (ECLIA), and the GnRH stimulation test results, which performed by obtaining venous blood samples at basal, 20 th , and 40 th minutes for FSH and LH measurement, were recorded. Results A total of 76 girls (38 CPP, 38 PT) were included. We detected an average peak LH cut-off value of 4.25 IU/L with 94.7 % sensitivity and 97.4 % specificity, a 97.3 % positive predictive value, and a 94.9 % negative predictive value in GnRH test to differentiate cases with CPP from PT. Conclusions This is the first study evaluating the diagnostic utility of the average of LH levels measured during GnRH stimulation test. We showed that the average of two LH measurements has a high diagnostic performance. Therefore, it can be used as a valid and reliable diagnostic tool for assessment of HPG axis activation, particularly for cases with a borderline peak LH level.

Objectives This study aimed to analyze the height growth pattern and the incidence of significant growth deceleration in girls with CPP and EFP on GnRHa treatment, and thereby identify relevant predictors of growth deceleration. Methods The data of 99 girls diagnosed with CPP and 47 girls with EFP were included in this retrospective analysis. The incidence of growth deceleration was calculated in both the first and second years. Multivariate logistic regression analysis was used to identify predictors indicative of growth deceleration. Results Growth velocity (GV) trajectories showed gradual decreases to the nadir at 18 months of treatment, and then they recovered till the 24th month of treatment, especially in girls with CPP. Nevertheless, the recovery was significantly greater in the CPP group than EFP. In the first year, no significant difference in the incidence of growth deceleration was found between the CPP group and the EFP group [17.35 vs. 25.53 %, p=0.249]; in the second year, the CPP group had a lower incidence than the EFP group [42.86 vs. 76.92 %, p=0.027]. The multivariate logistic regression analysis suggested that bone age (BA) was an independent predictor of growth deceleration (OR=2.264, 95 % CI: 1.268–4.042, p=0.006). The result of ROC curves showed the cut-off value of BA was 11.05 years. Conclusions GV varies at different periods during GnRHa treatment. GnRHa should be used with more caution for EFP treatment than for CPP. BA can be used to predict the occurrence of growth deceleration during GnRHa treatment.

Objectives Lymphedema (LD) in Turner syndrome (TS) is a commonly reported comorbidity, though its associations with karyotype and other comorbidities are poorly understood. Characteristics of patients with TS and LD, including correlation with phenotype and karyotype, are described. Methods Medical records of patients with TS seen in two pediatric institutions from 2002 to 2020 were retrospectively reviewed. Demographic data (age, presentation onset, clinical features, genetics, LD presence, investigations, treatments) were collected. Results 393 girls with TS with mean age of 12.5 years (SD: 5.7) were identified. LD was noted in 37 % of patients (n=146). Among the 112 patients with TS and documentation of onset of LD, LD was noted within the first year of life in 78.6 % (n=88). 67.6 % (n=96) of total patients with TS and LD had non-mosaic 45, X karyotype. Frequency of webbed neck was significantly greater in girls with TS and LD compared with girls without LD (58 vs. 7 %, p<0.001). Congenital heart anomalies, hypertension, and renal anomalies were also more common in girls with LD. Nail abnormalities with presence of hypoplastic or dysplastic nails were significantly associated with LD (OR: 6.784, 95 % CI 4.235–11.046). The number of girls reporting presence of LD decreased with age. Conclusions LD in TS often occurs within the first year of life, is less prevalent in older children and adolescents, and is significantly associated with 45, X karyotype, presence of webbed neck, nail changes, congenital heart anomalies, and renal anomalies.

Objectives This study aims to investigate the clinical features of differentiated thyroid carcinoma (DTC) in children and adolescents under 18 years and assess the impact of surgery combined with thyroid hormone and radioactive iodine (RAI) on their prognosis. Methods A retrospective observational study was conducted, involving children/adolescents with DTC who underwent surgery at the Head and Neck Department of Tianjin Medical University Cancer Institute and Hospital from January 1998 to December 2018. Results Among 198 patients, 130 (65.7 %) were female. According to the American Thyroid Association guidelines, cases were categorized as low (106, 53.5 %), intermediate (54, 27.3 %), and high (38, 19.2 %) risk. The follow-up duration ranged from 3 to 23 years. Local recurrence and distant metastasis were identified in 21 (10.6 %) and 14 (7.1 %) cases, respectively. All patients received levothyroxine, while RAI therapy was administered to intermediate- and high-risk patients. The local recurrence and distant metastasis rates in these two groups were 33.3 and 39.5 %, respectively, with no recurrence or metastasis in the low-risk group. Persistent without structural evidence of disease were 0.9, 3.7, and 26.3 % at end of follow-up for the low-, intermediate-, and high-risk groups, respectively. The overall survival rates for all three groups were 100 %, while disease-free survival rates were 99.1, 63.0, and 34.2 % for the low-, intermediate-, and high-risk groups, respectively. Conclusions Children/adolescents with low-risk DTC exhibited a favorable prognosis even without RAI. However, intermediate- and high-risk DTC patients, despite RAI and levothyroxine treatment, showed elevated rates of persistent disease, local recurrence, and distant metastasis.

Objectives Body esteem (BE) and quality of life (QOL) of girls aged 9–11 years may change depending on their puberty. We aimed to examine The Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) and the Body Esteem for Adolescents and Adults Scale (BESAA) for children. Methods The groups were determined as those whose puberty signs had not yet started (Group 1), those having with breast development stage 3 and/or larger (Group 2), and those who had received gonadotropin-releasing hormone agonist (GnRHa) treatment for at least 6 months (Group 3). Results A total of 145 girls (Group 1: 41, Group 2: 56, Group 3: 48), were included. The PedsQL scores of the Group 1 was higher than Group 2 (78.5 ± 10.3 vs. 70.1 ± 14.2; p=0.008). The PedsQL scores of the Group 1 was higher but not statistically different from Group 3 (78.5 ± 10.3 vs. 74.2 ± 14.3; p=0.401). The PedsQL scores of Group 2 was not statistically different from Group 3 (p=0.354). There was no statistical difference in BESAA scores between groups (p=0.291). Group 1’s PedsQL Health and Activity subscale score was higher than Group 2 (p=0.002). Conclusion The QOL of the girls with PP was found to be lower than their healthy peers. Health and Activity-related QOL scores were found to be lower in the untreated group, indicating that girls with PP were probably significantly disturbed by their puberty-related physical development at the onset of the disease.

Objectives To generate normative data and validate the recently developed, gender-neutral, External Genitalia Score (EGS) in Indian preterm and term neonates and children up to 2 years of age with normal and atypical genitalia. Methods This observational study included 1,040 neonates born between 28 and 42 weeks of gestation and 152 children between 1 and 24 months of age. In addition, 50 children with disorders of sex development (DSD) were also enrolled in the study. The Prader stage/external masculinization score (EMS) (as applicable), anogenital ratio (AGR) and EGS were assessed for all neonates and children with typical and atypical genitalia. Results Median EGS values in newborn males with typical genitalia were 9.5 at 28–31 weeks, 10.5 at 32–33 weeks, 11 at 34 weeks and 11.5 in males at 35–42 weeks of gestation. For all females with typical genitalia, the EGS was 0. EMS and EGS showed a positive correlation in males with typical genitalia (r=0.421, p=0.000**) and all children with DSD (r=0.857, p=0.000**). Mean AGR in males and females with typical genitalia and those with DSD were 0.52±0.07, 0.31±0.05 and 0.47±0.13, respectively. EGS correlated with AGR in all males with typical genitalia (r=0.107, p=0.008**), and in all children with DSD (r=0.473, p=0.001**). Conclusions The EGS enables accurate, gender-neutral and comprehensive assessment of external genitalia in Indian neonates and children with typical and atypical genitalia/DSD. Evaluation for DSD is recommended in any child with EGS greater than 0 and ≤10th percentile for gestation or age (10.5 in a term neonate).

Objectives Glycogen storage disease type V is caused by the mutations in muscle glycogen phosphorylase gene. This is the first report which DL-3-hydroxybutyric acid was used in combination with modified Atkins diet for the treatment of a patient with glycogen storage disease type V and quadriceps femoris shear wave elastography was performed to evaluate the treatment efficacy. Case presentation A 13-year-old girl was referred with fatigue and muscle cramps with exercise and there were no pathological findings in physical examination. Creatine kinase levels with 442 U/L. No phosphorylase enzyme activity was detected in muscle biopsy, a homozygous c.1A>G (p.M1V) pathogenic mutation was found in PYGM gene. She was started on DL-3-hydroxybutyric acid and modified Atkins diet at age 16. Her walking and stair climbing capacity increased, the need for rest during exercise decreased. The stiffness of the quadriceps femoris exhibited a reduction. Conclusions DL-3-hydroxybutyric acid and modified Atkins diet may provide an alternative fuel and shear wave elastography may be useful in demonstrating treatment efficacy. More clinical and pre-clinical studies are obviously needed to reach more definite conclusions.

Objectives To report an unusual case of thyroid abscess associated with thyroid dysfunction in an adolescent girl who has a normal anatomic structure of the thyroid gland. Case presentation A 15-year-old adolescent girl presented with a history of fever, sore throat, and neck swelling for 10 days duration. Contrast-enhanced computed tomography neck showed findings suggestive of an abscess involving the left lobe of the thyroid gland. She had low TSH and elevated T3 and T4 levels. Here, we report a case of thyroid abscess associated with transient hyperthyroidism in an immunocompetent girl who was successfully managed with parental antibiotics without incision and drainage. Conclusions Thyroid abscess can present with hyperthyroidism in children. So it is important to monitor all children who have thyroid abscesses for the development of permanent hypothyroidism later on. It’s important to diagnose this condition as soon as possible and begin antibiotic therapy appropriately.

Objectives Ovarian hyperthecosis (OHT) is a rare cause of severe hyperandrogenism in the adolescent age group. We describe two case reports, and present an approach to management in this age group based on a review of the literature. Case presentation Patient A presented at age 13 years with a 2 year history of androphonia and hirsuitism. Her testosterone level was elevated at 8.3 nmol/L, and there was marked enlargement of her ovaries bilaterally. There were no focal adrenal or ovarian lesions identified on imaging. She was treated with a gonadotropin releasing hormone (GnRH) agonist and spironolactone with biochemical and clinical improvement. Patient B presented at age 14 years with secondary amenorrhoea, and a 2 year history of androphonia, hirsutism and androgenetic alopecia. Her testosterone level was 12 nmol/L, and a pelvic ultrasound revealed numerous follicles in each ovary which were otherwise normal in size. She was managed with GnRH agonist initially, and now continues on a combined oral contraceptive pill. Conclusions Ovarian hyperthecosis needs to be considered in pre-menopausal women presenting with severe hyperandrogenism, after exclusion of androgen-producing adrenal and ovarian tumours. The principles of management in this age group are gonadotropin suppression and hormone replacement.

Objectives Lipoid congenital adrenal hyperplasia (LCAH) is a rare autosomal recessive disease caused by mutations in the steroidogenic acute regulatory protein ( STAR ) gene, expressed in the adrenal and gonadal tissues. In classical LCAH, individuals with 46, XY chromosomes present with a female appearance of the external genitalia due to insufficient androgen production. In the non-classical form, a milder phenotype is observed with male external genitalia. Here, we present a non-classical LCAH diagnosis with a newly identified c.266T>A (p.Ile89Asn) likely pathogenic homozygous variant in a 46, XY infant. Case presentation A three-month-and-thirteen-day-old male proband presented with clinical features of cortisol and mineralocorticoid deficiencies. The manifestation of salt-wasting syndrome occurred relatively late, and although the external genitalia appeared male, there was a mild virilization defect. The combination of mild impairment in androgen production and severe salt-wasting syndrome is an intriguing finding in our patient. Peripheral blood samples were obtained from the patient and his family. The newly identified variant, determined by next-generation sequencing analysis, was confirmed by segregation analysis showing carrier status in both parents. Conclusions We aim to contribute to the literature by elucidating molecular mechanisms by presenting an atypical presentation and a newly identified variant.