Band 29, Heft 4

Background: The aim of this study was to evaluate the effect of short-term vitamin D supplementation on the decline of residual beta cell function (RBCF) in children with type 1 diabetes (T1D). Methods: The study involved an intervention group (cholecalciferol 2000 IU/day and calcium 25 mg/kg/day for 6 months) comprising 15 children aged 6–12 years and within 1–2 years of diagnosis of T1D. Fifteen age-matched T1D patients were followed up as controls. Stimulated C-peptide levels were estimated at baseline and 6 months. Results : The mean decrease in stimulated C-peptide levels in the intervention group was lower (–0.048±0.15 ng/mL) as compared with the controls (–0.107±0.23 ng/mL) but did not reach statistical significance (p=0.472). The percent decrease in stimulated C-peptide from baseline to endpoint (8.3% vs. 20.3%, p=0.357) and the monthly decrease (0.008 ng/mL vs. 0.017 ng/mL, p=0.22) were non-significantly lower in the intervention group compared with the control group. Three (20%) patients progressed to undetectable stimulated C-peptide (≤0.01 ng/mL) over the study period in the control group as compared with one (6%) in the intervention group (p-value 0.260). Conclusions: There was a trend towards lesser decline of RBCF with short term cholecalciferol supplementation in children with T1D. Further larger studies are urgently needed to explore the beneficial effects of the relatively inexpensive vitamin D supplementation on RBCF.

Background: Sclerostin is a glycoprotein produced by osteocytes that is being evaluated as a potential clinical marker of bone turnover. The aim of this study was to investigate the association between neonatal vitamin D status and levels of circulating sclerostin. Methods: Forty newborns were recruited for the study. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D3 [25(OH)D] concentration <20 ng/mL and the newborns were divided into two groups as vitamin D deficient and vitamin D sufficient groups. Calcium, phosphate, alkaline phosphatase and sclerostin were measured at birth. Results: Newborns with vitamin D deficiency had markedly lower 25(OH)D levels than vitamin D sufficient newborns (8.5±4.4 ng/mL vs. 35.3±10.6 ng/mL, p<0.001). Vitamin D deficient infants also had significantly lower serum sclerostin levels (188.4±21.9 vs. 282.3±30.4 pg/mL; p: 0.026) than vitamin D sufficient newborns at birth. However, we did not detect a significant linear association between neonatal sclerostin and maternal/neonatal 25(OH)D levels. Conclusions: Our data also demonstrated that vitamin D deficient newborns exhibited lower sclerostin levels than vitamin D sufficient newborns. The low sclerostin level might serve as a marker of decreased osteocyte activity in newborns with vitamin D deficiency.

Background: Low vitamin D level is associated with adverse health outcomes and compromises HIV treatment response. We assess vitamin D status in HIV-infected Thai children receiving combination antiretroviral therapy (cART). Methods: A cross-sectional study in perinatally HIV-infected children. Vitamin D deficiency and vitamin D insufficiency were defined as serum 25-hydroxyvitamin D (25-OHD) level <20, and 21–29 ng/mL, respectively. Results: Eighty participants were enrolled. Their median age was 12.2 years. The median CD4 lymphocyte count was 784 cell/mm3; 95% had HIV RNA <50 copies/mL. The median (interquartile range, IQR) 25-OHD level was 33.5 (26.2–39.8) ng/mL. Thirty-four (43%) participants had low vitamin D level; 26 (33%) and 8 (10%) had vitamin D insufficiency and deficiency, respectively. In multivariate analysis, only geographic location was significantly associated with low vitamin D level. Conclusions: Most of perinatally HIV-infected children receiving cART had low vitamin D level. Calcium and vitamin D supplement might be beneficial.

Background: This study aimed to evaluate the efficacy and safety of a single monthly dose of cholecalciferol in healthy school children. Methods: A total of 118 children of class VI of a residential school were selected to receive vitamin D supplementation in the form of oral cholecalciferol 60,000 IU monthly. Serum calcium and 25-hydroxyvitamin D (25OHD) levels were estimated at 0 and 12 months. The proportion of subjects achieving vitamin D sufficiency was assessed. Results: The mean 25OHD levels increased significantly from 12.04±5.27 ng/mL at baseline to 32.6±7.05 ng/mL after 12 months of supplementation (p<0.001). None developed hypercalcemia. Conclusions: Vitamin D supplementation in the doses of 60,000 IU monthly is a reasonable, safe and cost-effective regimen for children to attain and maintain vitamin D sufficiency.

Background: We aimed to assess the association between exposure to sunshine during gestation and the risk of type 1 diabetes (T1D) in Danish children. Methods: The study population included 331,623 individuals born in Denmark from 1983 to 1988; 886 (0.26%) developed T1D by the age of 15 years. The values of sunshine hours were obtained from the Danish Meteorological Institute. Gestational exposure to sunshine was calculated by summing recorded monthly sunshine hours during the full 9 months prior to the month of birth. The linear variable then was split into two categories separated by the median value. Results and Conclusions: Cox regression models showed that more sunshine during the third gestational trimester was associated with lower hazards (HR) of T1D at age 5–9 years in males: HR (95% CI): 0.60 (0.43–0.84), p=0.003. Our results should be considered in the context of evidence-based recommendations to the public about skin protection from the sun.

Slipped capital femoral epiphysis (SCFE) is a relatively common hip disorder often seen in overweight, peripubertal children. Although the exact etiology is uncertain, it is generally accepted that underlying endocrinopathies play a role in the pathogenesis. Hypothyroidism is the endocrine disorder cited most commonly in association with SCFE, and patients often have no history of thyroid dysfunction at the time of presentation. Despite being a well-recognized risk factor, recommendations for screening thyroid function in patients with typical presentations of SCFE have not been deemed cost-effective; however, there is data to support screening for hypothyroidism in patients with atypical presentations of SCFE or short stature. Hypothyroidism may have a significant impact on healing and bone union after surgical management of SCFE and there is a paucity of case reports in the literature describing potential peri- and postoperative complications. We performed a systematic review of the literature of all reported cases of SCFE with associated hypothyroidism using the search terms, which demonstrated a physiologic relationship between hypothyroidism and SCFE. Two case reports of SCFE in patients with hypothyroidism and associated complications are presented with the literature review. There is a physiologic relationship between thyroid dysfunction and SCFE, and we postulate that profound hypothyroidism may contribute to delayed healing or nonunion in patients undergoing operative management. We support the recommendation to screen patients with short stature, atypical presentation of SCFE, or perisistent nonunion after surgery. In cases of hypothyroidism, we recommend thyroid hormone replacement and laboratory confirmation of return to euthyroid state prior to operative intervention.

Background: The aim of this study is to determine the relationship between oxidative stress marker (8-iso-prostaglandine F 2α ) and glycemic indices computed from daily glucose monitoring data in children with type 1 diabetes mellitus (T1DM). Methods: Thirty-one children and adolescents with T1DM (median age 12.2 years) and healthy subjects (median age 11.7 years) were enrolled into the study. Anthropometric data were recorded for the entire group before the study. In addition, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA 1c were recorded in T1DM subjects. T1DM subjects performed self-monitoring of blood glucose (SMBG) for a month (at least four times a day) for calculating glycemic indices. Twenty-four-hour urine 8-iso-prostoglandine F 2α levels were studied at the end of the study period in the both groups. Results: Median diabetes duration was 5 years, hemoglobin A 1c (HbA 1c ) was 7.3%. Standard deviation (SD) of the blood glucose (BG) was determined as 85 mg/dL. Median urinary 8-iso-prostoglandine F 2α was found to be significantly higher than that of the healthy subjects (2808.9 and 298 pg/mg creatinine, p<0.001, respectively). There was no correlation between urinary 8-iso-prostoglandine F 2α and age, anthropometric data, diabetes duration, insulin requirement, lipid values, microalbuminuria, HbA 1c , or SD of BG in T1DM groups. Conclusions: This study showed that, 8-iso-prostoglandine F 2α that is an oxidative stress marker, is significantly higher in T1DM than that of healthy subjects while, no significant relation between glycemic indices and urinary 8-iso-prostoglandine F 2α levels were demonstrated. Further studies are needed to assess other factors, and the relationship between glucose fluctuations and oxidative stress markers.

Background: We evaluated the relationship between an early inflammatory biomarker, chemokine (C-C motif) ligand 2 (CCL2), and other clinical biomarkers and lifestyle behaviors, in overweight/obese adolescents at high risk of developing cardiometabolic derangements. Methods: We collected anthropometric measurements, clinical biomarkers, and three 24-h dietary recalls from 21 vocational high school students (91% male), 14–19 years, with body mass index (BMI) ≥25 kg/m 2 . Pearson’s or Spearman’s correlation coefficients were used to examine relationships. Results: Mean BMI was 33.2 kg/m 2 (range 25.7–45.6) and 38% were prediabetic by fasting glucose. Mean CCL2 was 512.9 pg/mL (range 220–917) and positively correlated with triglycerides (r=0.45; p=0.04) and TNF-α (r=0.57; p=0.007) and marginally negatively correlated with fruit/vegetable intake (r=–0.42, p=0.06) and omega-3 fatty acids (r=–0.41, p=0.07). Conclusions: CCL2 was positively associated with pro-inflammatory biomarkers and negatively associated with some anti-inflammatory dietary factors.

Background: The metabolic syndrome (MS) in pediatrics is controversial. Rather than a dichotomous scale, a continuous metabolic syndrome score (cMets) has been proposed to evaluate MS. The aim of this study was to evaluate the utility of a cMets score among an ethnically diverse cohort of children with acanthosis nigricans (AN). Methods: A retrospective chart review was used to extract clinical and laboratory information on a cohort of obese children. Criteria for MS components and the cMets score were established using published guidelines. Multiple linear regression evaluated the effect of AN status on MS and cMets. Fisher’s exact test compared the race differential on the presence or absence of MS component disorders. Results: MS diagnosis was non-significant when considering AN status (p=0.554) and ethnicity (p=0.431). Evaluation of the frequency of component disorders, revealed that Caucasians had significantly higher levels of abnormal triglycerides (TG) (35.1 vs. 10.3%; p<0.001), whereas African Americans had significantly higher homeostatic model assessment of insulin resistance (HOMA-IR) scores (51.3% vs. 22.3%; p<0.001). cMets was sensitive to identifying metabolic risk among Caucasians with AN, only (p=0.029). Conclusions: This study found differences in health risk among an obese, ethnically diverse sample of children. cMets is a more sensitive marker of metabolic change compared with MS, especially when AN status and race are considered. cMets may pose an opportunity for the clinician to evaluate the interaction of health risks on the health status of obese children.

Background: Hypertension is the leading cause of cardiovascular disease worldwide, and both high and low blood pressures are associated with various chronic diseases. Thyroid hormones have profound effects on cardiovascular function, including on blood pressure. Recent studies have shown that childhood hypertension can lead to adult hypertension. Therefore, adequate blood pressure control is important from early life. Employing a life-course approach, we aimed to investigate the association between thyroid hormones and blood pressure in children. Methods: A total of 290 children from the Ewha Woman’s University Hospital birth cohort participated in a preadolescent check-up program. We assessed the levels of serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) and the blood pressure status in these children. Thyroid hormone concentrations were measured using an electro-chemiluminescence immunoassay (ECLIA), and hypertension was defined according to the guideline of the Korea Centers for Disease Control and Prevention. Results: The sex-, age-, and height-adjusted prevalence of hypertension was 27.0% in the present study. On regression analysis, serum FT4 showed significantly negative association with diastolic blood pressure (DBP; β=–8.24, 95% CI: –14.19–2.28, p=0.007). However, these relationships were not significant after adjustment for sex, age, and current body mass index. The levels of serum TSH showed no relationship with mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) after adjustment. No significant differences in serum TSH and FT4 levels according to hypertension status were found. Conclusions: These findings suggest that thyroid hormone is not independently associated with increased blood pressure in euthyroid preadolescents.

Background: The aim of the study was to evaluate the etiology, the role of pubertal timing and most useful criteria for diagnostic workup in adolescents with growth failure. Methods: Adolescents (n=182) aged 10.0–18.0 years underwent a standardized diagnostic protocol. Constitutional delay of growth and puberty (CDGP) was defined as late pubertal onset or a Tanner stage less than –2 SDS. Dutch and Finnish criteria for growth monitoring were retrospectively assessed. Results: In 13 children (7.1%) a specific diagnosis could be established. CDGP was diagnosed in 10% of patients aged ≥13 (girls) or ≥14 years (boys). Sensitivity to detect pathologic causes was 85% and 62% for, respectively Dutch and Finnish criteria for growth monitoring as used in younger children, but specificity was low (55%–59%). Conclusions: In adolescents, pathological causes for growth failure and pubertal delay are common, and we recommend a combination of height SDS, distance to THSDS and growth deflection for deciding on further diagnostic testing.

Background: Phenotypic variability of Turner syndrome (TS) challenges clinicians, and undiagnosed mosaicism may lead to conflicting results of karyotype-phenotype correlations. This study assessed the extent of phenotypic variability and investigated the presence of karyotype-phenotype correlations. Methods: The sample comprised 80 patients with ≥50 cells analyzed in karyotype. Twenty were 45,X/46,X,+mar; three groups of 20 patients were constructed by matching those girls with the nearest-aged patient with 45,X, 45,X/46,XX and 45,X/46,X,i(Xq) or 46,X,i(Xq) karyotype. Results: Data were obtained on height z-score, dysmorphic features, echocardiogram and urinary system sonography. The number of dysmorphic features ranged from one to 16 and was not correlated to age at diagnosis or height. The groups did not differ in height, number of dysmorphic features, cardiovascular and urinary system anomalies and frequency of any specific feature, except for short fourth metacarpal. Conclusions: Wide phenotypical variability of TS may be objectively described and its clinical picture is not correlated to karyotype.

Background: Glutathione synthetase (GS) deficiency is a rare inborn error of glutathione (GSH) metabolism manifested by severe metabolic acidosis, hemolytic anemia, neurological problems and massive excretion of pyroglutamic acid (5-oxoproline) in the urine. The disorder has mild, moderate, and severe clinical variants. We aimed to report clinical and laboratory findings of four patients, effect of sodium hydrogen carbonate treatment and long-term follow up of three patients. Methods: Urine organic acid analysis was performed with gas chromatography-mass spectrometry. Molecular genetic analysis was performed in three patients, mutation was found in two of them. Enzyme analysis was performed in one patient. Clinical and laboratory findings of four patients were evaluated. Results: One patient died at 4 months old, one patient’s growth and development are normal, two patients have developed intellectual disability and seizures in the long term follow up period. Three patients benefited from sodium hydrogen carbonate treatment. Conclusions: The clinical picture varies from patient to patient, so it is difficult to predict the prognosis and the effectiveness of treatment protocols. We reported long term follow up of four patients and demonstrated that sodium hydrogen carbonate is effective for treatment of chronic metabolic acidosis in GS deficieny.

Background: Maturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11 MODY genes in Turkish children by using targeted next generation sequencing. Methods: A panel of 11 MODY genes were screened in 43 children with MODY diagnosed by clinical criterias. Studies of index cases was done with MISEQ-ILLUMINA, and family screenings and confirmation studies of mutations was done by Sanger sequencing. Results: We identified 28 (65%) point mutations among 43 patients. Eighteen patients have GCK mutations, four have HNF1A , one has HNF4A , one has HNF1B , two have NEUROD1 , one has PDX1 gene variations and one patient has both HNF1A and HNF4A heterozygote mutations. Conclusions: This is the first study including molecular studies of 11 MODY genes in Turkish children. GCK is the most frequent type of MODY in our study population. Very high frequency of novel mutations (42%) in our study population, supports that in heterogenous disorders like MODY sequence analysis provides rapid, cost effective and accurate genetic diagnosis.

Growth hormone (GH) secreting adenoma represents a therapeutic challenge in childhood. Because of its rarity no treatment guidelines are available and pediatric management often results from recommendations issued for adults. We report a case of a 4-year-old girl with somatotropinoma successfully treated with only medical treatment. She presented with tall stature and history of growth acceleration. Imaging and laboratory confirmed the diagnosis of GH secreting macroadenoma. She started medical treatment with a somatostatin analogue and a dopamine agonist. During an 8-year follow-up period, a good clinical control of the disease and a shrinkage of the adenoma have been demonstrated. At the last observation she achieved normal near-adult height and pubertal development. According to our experience and limited literature evidences, first line treatment with somatostatin analogues can be attempted in patients with somatotropinoma. This approach seems to be able to control the clinical course of the disease, allowing to postpone transphenoidal surgery to adult age or to avoid it.

Adrenocortical tumors are neoplasms that rarely occur in pediatric patients. Adrenocortical carcinoma (ACC) is even more uncommon, and is an aggressive malignancy with 5-year survival of 55% in a registry series. There is a lack of information on long-term endocrine outcome in survivors. We describe a 10-year follow-up in a patient who presented at 3 years 5 months with a 1-year history of axillary odor and 6 months’ history of pubic hair development with an increased clitoral size. Androgen levels were increased and a pelvic sonogram revealed a suprarenal mass of the left kidney. The tumor was successfully removed. At 6 years 11 months, androgen levels increased again. Workup for tumor recurrence was negative and the findings likely represented early adrenarche. The patient had menarche at an appropriate time and attained a height appropriate for her family.