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Background Diabetes has previously been linked to mental health problems in children and adolescents, but more recent studies have yielded mixed findings. The aim of the current study was to compare symptoms of mental health problems in children and adolescents with and without type 1 diabetes (T1DM). Methods Life quality, subjective well-being, self-rated health, depression and somatic symptoms in children and adolescents with diabetes (n=130) were measured and compared to the results of a socio-demographically joined control group (n=177) which consists of healthy children and adolescents. Results A significant difference could be observed between the groups in well-being and depressive symptoms as according to the results, the research sample namely the children with T1DM could be described with significantly higher subjective well-being and mood, but with less physical symptoms and lower level of depression as those in the control group. Conclusions These findings suggest that T1DM is not associated with an increased risk of psychosocial problems, and confirm that even a severe disease of a child can lead to personal growth.

Background Therapeutic goals have been established to decrease the risk of long-term complications of type 1 diabetes (T1DM). The effects of these guidelines should be constantly evaluated. Hence, the present study examines the frequency at which children with T1DM treated by one of the Polish reference centers complied with the therapeutic targets issued in 2014 by the International Society for Pediatric and Adolescent Diabetes (ISPAD) and by the Diabetes Poland (PTD). Methods A retrospective analysis (years 2011–2014) was performed in patients with T1DM aged 6.5–18 years, with diabetes duration >12 months and no change of insulin regimen within 6 months. Collected data included insulin therapy regimen, weight, height, blood pressure, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and glycated hemoglobin (HbA 1c ) level from the last hospitalization. Results The records of 447 patients (260 boys, 299 treated with insulin pump) were analyzed. All ISPAD goals were achieved by 123 (27.5%) patients, but only 43 (9.6%) met all PTD targets. Optimal HbA 1c was achieved by 224 (50.1%) according to ISPAD criteria (HbA 1c <7.5%) and by 87 (19.6%) patients according to PTD (HbA 1c ≤6.5%). Obesity was diagnosed in 11.6% of the patients; 19.7% of the patients were overweight. In logistic regression, patient age was the only independent predictor of failing to achieve complete T1DM control (p=0.001, OR=1.12 [1.05–1.23]) and optimal HbA 1c (p=0.01, OR=1.1 [1.0–1.2]) according to ISPAD guidelines. Moreover, girls had a greater risk of failing body mass index (BMI) targets (PTD: p=0.002, OR=2.16; ISPAD: p=0.0001, OR=3.37) and LDL-C targets (p=0.005, OR=1.8) than boys. Conclusions Overall, control of vascular risk factors in Polish children with T1DM is unsatisfactory. While too few children are achieving the HbA 1c target set by PTD, it is possible that such strict national target helps half of the Polish school-age patients achieve ISPAD-issued aim which is more liberal. High prevalence of overweight among children with T1DM warrants initiatives focused not only on glycemic control but also on motivation of patients to lead a healthy lifestyle.

Background Aquaporin 7 (AQP7), a water/glycerol transporting protein, regulates adipocyte glycerol efflux and influences lipid and glucose homeostasis. Altered AQP7 expression in adults leads to impaired glycerol dynamics, adipocyte hypertrophy and it predisposes them to obesity and diabetes. To assess its possible involvement in childhood obesity, this study investigated the expression of adipocyte AQP7 in cultured adipocytes of children. Methods Primary in vitro differentiated adipocyte cultures were developed from surgical biopsies of subcutaneous abdominal adipose tissue from 61 (46 prepubertal, 15 pubertal) lean children (body mass index [BMI] <85%) and 41 (22 prepubertal, 19 pubertal) children with obesity (BMI >95%). AQP7 expression was studied by reverse transcription polymerase chain reaction and Western immunoblotting and insulin by enzyme-linked immunosorbent assay. Results AQP7 messenger RNA (mRNA) was increased in the younger obese prepubertal (YOP) children but decreased in the obese adolescents (OA) (p=0.014) who also had increased insulin and homeostatic model assessment – insulin resistance (HOMA-IR). Lean pubertal (LP) children and YOP had increased 41 kDa AQP7 protein expression (p=0.001 and p=0.005, respectively). The OA who expressed 34 kDa AQP7 had lower triglyceride (TG) levels than those who did not express it (p=0.013). In the lean children, TG were negatively correlated with 34 kDa AQP7 (p=0.033). Conclusions The lower AQP7 mRNA expression in the OA may reflect a predisposition to adipocyte hypertrophy and metabolic dysfunction, as in the adults, whereas the YOP may be protected from this. The increased 41 kDa AQP7 protein expression in the LP may reflect the increased energy requirements of puberty for glycerol while in the YOP it may also be protective against the development of adipocyte hypertrophy.

Background There are no studies on the use of complementary and alternative medicine (CAM) therapies in subjects with inherited metabolic disease (IMD) in the current literature. This study aimed to determine the type, frequency of and reasons for the use, and factors associated with the use of CAM therapies. Methods Subjects included in this study consisted of 335 children (95.7%) and 15 (4.3%) adults with a median age of 5.66±6.16 (0.08–48) years with inherited metabolic disease. A single physician conducted face-to-face interviews with the mother and/or father for pediatric subjects and with the subjects themselves for adults of a normal intelligence. Data were obtained from responses to the questions in the standard survey form. Results Our study included 350 patients in total, of whom 164 (46.9%) were female and 186 (53.1%) male. We found that 144 of the patients (41.1%) had used at least one CAM therapy method. The highest rate of use among the CAM therapy methods was of the mind-body approach therapies (n=98, 28%). This was followed by biologically-based (n=75, 21.4%) and manipulative and body-based (n=5, 1.4%) therapies, respectively. The most commonly used herbal product was herbal tea (n=21, 6%), and the most commonly used dietary supplementation was a royal jelly and pollen mixture (n=9, 2.6%). Significant differences in the subjects’ age, their follow-up duration, their mother’s and father’s ages, and CAM therapy use were identified from sociodemographic data. Conclusions In our study, the use of CAM therapies was determined at a high rate. This is important when dealing with clinical problems and for clinicians who follow-up with IMD subjects and suspect they may be using CAM therapy.

Background Maternal diet and gestational age of infant may affect the composition of breast milk. The aim of this study was to evaluate the relationship between breast milk adiponectin and leptin levels of mothers delivering preterm and term infants and maternal diet. Methods Sixty-five mothers (31 preterm, 34 term) were included in the study. General information about parents and infants and food consumption of mothers were determined through a questionnaire. Milk samples were taken from mothers during the period between the 15th and 30th day after birth (mature milk). For the evaluation of maternal diet, the nutrient adequacy ratio (NAR) and mean adequacy ratio (MAR) were used. Results According to MAR, 71.0% of preterm mothers’ and 79.4% of term mothers’ dietary adequacy was categorized as “good”, and none of the mothers fell into the “insufficient” category (p>0.05). The median (interquartile range [IQR]) level of adipokines was found to be higher in preterm than in term mothers (24.6 [14.3] ng/mL; 22.9 [9.7] ng/mL for adiponectin and 2.0 [2.5] ng/mL; 0.0 [2.3] ng/mL for leptin, respectively) (p>0.05). A negative correlation was found between the leptin level and intake of unsaturated fatty acids, protein NAR and meat, poultry and fish consumption in preterm mothers (p<0.05). A positive correlation was found between leptin concentration and MAR, protein, calcium, potassium NAR and consumption of dairy products in term mothers (p<0.05). In the regression model, gestational age and MAR are important predictors of leptin. Conclusions These results show that maternal diet is related to the leptin content in breast milk.

Background Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the gold standard for the measurement of serum 25-hydroxyvitamin D (25(OH)D) levels instead of the conventional method, radioimmunoassay (RIA). However, there was no study that compared RIA and LC-MS/MS for measuring serum 25(OH)D levels in infants and their mothers. The aim of this study was to assess the agreement of RIA and LC-MS/MS for measuring the serum levels in infants and postpartum women. Methods This study enrolled 70 preterm infants, 113 term infants (134 samples), and 120 postpartum women. Serum concentration of 25(OH)D was measured by RIA and LC-MS/MS. We evaluated the correlation between RIA and LC-MS/MS. Also, we evaluated the bias between RIA and LC-MS/MS using Bland-Altman analysis. Results Sixty percent of preterm infants had serum 25(OH)D levels below the lower limit of quantification (LOQ) (4 ng/mL) and 90% of them were classified as vitamin D deficient. The serum 25(OH)D levels measured by RIA were significantly correlated with those measured by LC-MS/MS in all groups. According to the Bland-Altman plot, the serum 25(OH)D levels of infants measured by RIA had constant positive bias (mean±standard deviation [SD] [95% confidence interval, CI], preterm: +4.8± 2.4 ng/mL [4.2–5.4], term: +5.8±4.0 [5.1–6.5]) and proportional bias (preterm: r =0.44, p<0.01, term: r =0.50, p<0.01) compared with LC-MS/MS. The serum 25(OH)D levels of postpartum women measured by RIA had constant positive bias compared with LC-MS/MS, but no proportional bias was found. Conclusions RIA demonstrated falsely high 25(OH)D levels when used for infants and postpartum women.

Background: Prompt intervention can prevent permanent adverse neurological effects caused by neonatal hypothyroidism. Thyroid function changes rapidly in the first few days of life but well-defined age-specific reference intervals (RIs) for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free tri-iodothyronine (FT3) are not available to aid interpretation. We developed hour-based RIs using data mining. Methods: All TSH, FT4 and FT3 results with date and time of collection from neonates aged <7 days during 2005–2015 were extracted from the Monash Pathology database. Neonates with more than one episode of testing or with known primary hypothyroidism, identified by treating physicians or from medical records, were excluded from the analysis. The date and time of birth were obtained from the medical records. Results: Of the 728 neonates qualifying for the study, 569 had time of birth available. All 569 had TSH, 415 had FT4 and 146 had FT3 results. For age ≤24 h, 25–48 h, 49–72 h, 73–96 h, 97–120 h, 121–144 h and 145–168 h of life, the TSH RIs (2.5th–97.5th) (mIU/L) were 4.1–40.2, 3.2–29.6, 2.6–17.3, 2.2–14.7, 1.8–14.2, 1.4–12.7 and 1.0–8.3, respectively; the FT4 RIs (mean ± 2 standard deviation [SD]) (pmol/L) were 15.3–43.6, 14.7–53.2, 16.5–45.5, 17.8–39.4, 15.3–32.1, 14.5–32.6 and 13.9–30.9, respectively; the FT3 RIs (mean±2 SD) (pmol/L) were 5.0–9.4, 4.1–9.1, 2.8–7.8, 2.9–7.8, 3.5–7.2, 3.4–8.0 and 3.8–7.9, respectively. Conclusions: TSH and FT4 were substantially high in the first 24 h after birth followed by a rapid decline over the subsequent 168 h. Use of hour-based RIs in newborns allows for more accurate identification of neonates who are at risk of hypothyroidism.

Background Until the American Thyroid Association (ATA) guidelines on management of pediatric differentiated thyroid carcinoma (DTC) became available in 2015, all children with DTC were treated like adults. This study aims to investigate the outcome of pediatric DTC and factors predicting the response to therapy in pediatric DTC managed according to adult guidelines. Methods Clinical records of 41 children less than 18 years of age diagnosed with DTC followed from 2007 in a single center were reviewed. According to the new ATA classification for pediatric DTC, five had low-risk, 28 had intermediate-risk and eight had high-risk disease at presentation. Results There was no mortality or recurrence in this cohort of pediatric DTC patients and the cure rate was 46% during a mean follow-up of 44 months when they were managed according to adult guidelines. Neither the new ATA risk classification nor any clinicopathological character was identified which could predict the response to therapy. The new ATA guidelines would have avoided 27% of the radioiodine therapies given. Conclusions This study showed that DTC in children managed according to adult guidelines had a good cure rate. The new ATA guidelines on pediatric DTC might have drastically reduced the number of radioiodine therapies in the affected children. Long term prospective studies are needed to validate the benefits and risks of both these approaches.

Background The aim of this study was to analyze the seasonal birth month pattern in young patients with autoimmune thyroiditis and compare it with youth controls. Methods Medical records of a total of 298 children and adolescents of Greek origin, with a diagnosis of Hashimoto thyroiditis (HT) before the age of 21 years that were born from 1987 to 2010 were retrospectively reviewed. In addition, 298 consecutive subjects that were born from 1988 to 2012 and evaluated in a tertiary unit for any reason, served as controls, provided that they had no personal or family history of thyroid or any other autoimmune disease. Results Significant differences were found between children and adolescents with HT and healthy controls in the yearly pattern of month of birth distribution (p=0.029). During month-by-month analysis, it was shown that the highest and lowest predispositions to HT were among those born in spring (March) (odds ratio [OR] 2.34, p=0.005), and autumn (November) (OR 0.49, p=0.035), respectively. A binary logistic regression model also revealed that season of birth and sex were the only factors that remained related to HT disease, even after adjustment for confounding factors such as year of birth and age (p<0.001, Nagelkerke r-square 0.151). Conclusions This study suggests that the effect of certain seasonal factors during fetal development, reflected by the seasonal differences in birth pattern, in children and adolescents with autoimmune thyroiditis could contribute to long-term programming of an autoimmune response against the thyroid gland. Further studies are needed to demonstrate a clear cause and effect relationship between month of birth and HT.

Background The aim of our study was to evaluate clinical, laboratory and imaging findings and to have an idea about the clinical course of subclinical hypothyroidism in children. Methods Our study included 25 patients who were diagnosed with non-autoimmune subclinical hypothyroidism without goitre, between the ages of 3 and 18 and with body mass index (BMI) below the 85th percentile. Results The mean thyroid-stimulating hormone (TSH) level was 6.92±0.92 μIU/mL at diagnosis, 4.77±1.57 μIU/mL in the third month and 4.51±1.79 μIU/mL in the first year of follow-up. About 73.7% of subclinical hypothyroidism was recovered. There was no statistically significant difference between heart rate, diastolic blood pressure, lipid profile, fasting blood glucose (FBG), fasting insulin level, homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin, white blood cell, platelet, C-reactive protein (CRP) levels and thyroid volume at diagnosis and in the first year of follow-up. In the first year of follow-up, systolic blood pressure and high-sensitivity CRP value were significantly higher than at diagnosis. However, it was observed that these values were similar in the present group with subclinical hypothyroidism. Conclusions We concluded that there was no progression to overt hypothyroidism during 1-year follow-up and that subclinical hypothyroidism had no effect on height standard deviation score (SDS), BMI SDS, blood pressure, glucose and lipid metabolism during follow-up without treatment.

Background Cystic fibrosis-related diabetes (CFRD) is a common comorbidity reported in patients with cystic fibrosis (CF). There is a dearth of data on glucose intolerance or CFRD in children with CF from developing countries. So, we planned to study the prevalence of abnormal glucose tolerance (AGT) in children with CF and its relation with the duration and severity of CF. Methods We performed an oral glucose tolerance test (OGTT) on children (2–18 years old) having CF for at least 6 months. Two-hour plasma glucose levels on OGTT were correlated with various disease-related factors. Results Out of the 25 children enrolled, there were 18 boys and seven girls. The mean age and duration of CF were 7.9±4.3 and 3.16±2.5 years, respectively. AGT was observed in 16 (64%) children with CF including three (12%) children with CFRD. Children with a duration of CF of 3 years had significantly higher prevalence (81.8%) of AGT when compared with duration ≤3 years (p-value<0.05). Twelve out of 17 (70.6%) children were colonized with Pseudomonas and 12 out of 15 (80%) children >6 years of age had AGT. There was a positive correlation of 2-h glucose value on OGTT with duration of CF and number of hospitalizations with acute pulmonary exacerbations. Conclusions The majority of children having CF for >3 years and/or age >6 years developed AGT. In our clinical setting, an annual screening with OGTT to detect AGT may be required at an early age and duration of CF.

Background Gynaecomastia, although rarely related to testicular tumours, in boys with Peutz-Jeghers syndrome (PJS) usually occurs due to large-cell calcifying Sertoli cell tumour (LCCSCT). Case presentation A 4-year-old boy, with a genetic diagnosis of PJS, presented gynaecomastia since the age of 2, associated with increased height velocity (HV). He exhibited bilateral breast enlargement (Tanner-B4) and a testicular volume of 4 mL. Testicular ultrasound revealed multifocal microcalcifications in both testicles. A laboratory evaluation showed undetectable gonadotrophins, testosterone and oestrogen and inhibin A of 4.6 pg/mL (0.9–1.7). The boy was subjected to therapy with anastrozole. In the last follow-up, 2 years after the start of therapy, he experienced a less tense Tanner-B2 and a decrease in HV; serum inhibin A had become negative. Conclusions This is one of the most precocious PJS-related gynaecomastia treated with aromatase inhibitors (AIs) reported in the literature. Oestrogen levels, although under the detection limit, may be sufficient to stimulate breast tissue/growth plates. Inhibin A is a good marker of LCCSCT and an indicator of response to AIs.

Background Infantile free sialic acid storage disease (ISSD) is a severe multisystemic disorder characterized by the accumulation of free sialic acid in lysosomes. Case presentation The patient presented prenatally with fetal ascites and large scrotal hernias, without pleural or pericardial effusion. During the infantile period, he was diagnosed with permanent isolated immunoglobulin G (IgG) hypogammaglobulinemia, which thus far has rarely been associated with ISSD. The analysis of the SLC17A5 gene revealed a novel homozygous 94 bp gene deletion. We further provide a detailed description of pre- and postnatal clinical and radiographic findings. Conclusions Fetal ascites could be the first sign of several lysosomal storage diseases (LSDs), including ISSD. The analysis of LSD gene panels is an effective approach to diagnosis in the case of non-specific symptoms and when specific biochemical tests are not easily available.

Background Xanthogranuloma of the sellar region is a rare entity. Its pathology is controversial and it is difficult to strictly differentiate it from craniopharyngioma or Rathke’s cyst. Case presentation We report a case of xanthogranuloma accompanied by growth hormone deficiency in an 11-year-old girl. She did not show any other pituitary hormone deficiency or neurological symptoms before operation. The preoperative diagnosis was craniopharyngioma, but histological findings showed small areas of epithelium. Thus, the final diagnosis was xanthogranuloma. Xanthogranuloma is an important cause of growth delay. We reviewed 16 cases reported after 2000, and included our case, of xanthogranuloma in children. Conclusions Endocrinological symptoms are often regarded as one of the few apparent symptoms in xanthogranuloma compared with craniopharyngioma. Therefore, we should follow up carefully and accumulate cases.

Background The association of hyperthyroidism with renal disease is very rare and the importance of timely clinical recognition cannot be overemphasized. Case presentation An 11-year-old girl presented with gastrointestinal symptoms while hypertension, edema and abdominal pain were noticed on clinical examination. Laboratory investigation revealed: hemoglobin 9.4 (11.5–15.5) g/dL, total white cell count 16 (4.5–12)×10 9 /L, platelets 247 (150–450)×10 9 /L, C-reactive protein (CRP) 31.8 (<5) mg/L, blood urea nitrogen (BUN) 126 (13–43) mg/dL, creatinine 0.98 (0.53–0.79) mg/dL, albumin 25 (35–52) g/dL, complement factor C3 0.7 (0.9–1.8) g/L, complement factor C4 0.1 (0.1–0.4) g/L, tri-iodothyronine 6.5 (2.5–5.2) pg/mL, free thyroxine 2.4 (1–1.7) ng/dL, thyroid stimulating hormone (TSH) <0.02 (0.5–4.3) mU/L. Urinalysis showed nephrotic range proteinuria. Renal function deteriorated necessitating hemodialysis (HD). A renal biopsy revealed an immune complex-mediated membranoproliferative glomerulonephritis (MPGN). Elevated thyroid hormones and suppressed TSH levels with elevated thyroperoxidase antibodies and thyroid stimulating immunoglobulins confirmed the diagnosis of Graves’ disease. Corticosteroids were commenced and eventually thiamazole was added with gradual improvement of renal function, cessation of HD and discharge from the hospital. Conclusions Graves’ disease complicated by MPGN is extremely rare, but can cause life-threatening complications.