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Background. There is an increased risk for childhood type 1 diabetes (T1D) when T1D and type 2 diabetes (T2D) are reported in relatives. Objectives. Our objective was to evaluate current family risk factors for T1D development before implementing a national screening program for T1D. Materials and methods. A population of 879 Caucasian children and adolescents with T1D and 286 healthy controls were enrolled in the study. All participants completed the same questionnaire, which collected information about family history of diabetes over 3 generations. In statistical analyses, frequency tables and Χ2 tests evaluated possible multicollinearity among risk factors that were significantly associated with the outcomes. Results. Family history of diabetes was more frequent in controls (n = 75, 26.2%) than in patients with T1D (n = 146, 16.6%, odds ratio (OR) = 1.785, 95% confidence interval (95% CI): 1.299-2.452, degrees of freedom (df) = 12.976, p = 0.004), especially with a family history of T2D (n = 62, 21.7% compared to n = 79, 9.0%, respectively, OR = 2.803, 95% CI: 1.948-4.034, df = 32.669, p < 0.001). Also, there was a tendency for the nuclear family of T1D patients to be more frequently affected by T1D (n = 74, 8.4%) than the controls (n = 15, 5.2%, OR = 1.605, 95% CI: 0.937-2.751, df = 3.081, p = 0.079). The risk of T1D was associated with the closest family members being affected and accelerated over generations. Indeed, it was highest in siblings, especially brothers (OR = 12.985, 95% CI: 0.782-215.743, Fisher's test: p < 0.001). A positive family history of T2D burden among second-degree relatives was 2.728 times more frequent in the control group than in the T1D group (OR = 2.728; 95% Cl: 1.880-3.962, p < 0.001). Furthermore, a positive family history of T1D among first-degree relatives was less frequent in the controls than in the T1D group (OR = 0.124; 95% Cl: 0.030-0.516, p = 0.004). Conclusions. A family history of T1D, but not T2D, is a significant risk factor for T1D development. Indeed, the priority in screening for T1D should be given to first-degree relatives of T1D patients, starting from siblings. [ABSTRACT FROM AUTHOR]

Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study is to analyze patients who do not respond adequately to human recombinant growth hormone (rhGH) treatment. Material and methods: Four boys were analyzed: three patients diagnosed with SNP at the ages of 1) 8 years and 2 months, 2) 13 years and 2 months, 3) 16 years and 6 months, and patient 4) at the age of 6 years and 11 months - born small for gestational age (SGA). They underwent rhGH treatment. Results: The expected growth improvement was not observed in all boys. Patient 1 was diagnosed with aortic coarctation, and after each attempt to increase the rhGH dose, nocturnal vomiting occurred - epilepsy was diagnosed. Patient 2 had severe foot pain. Patient 3 had delayed puberty - hypogonadotropic hypogonadism was diagnosed. Patient 4 had dysmorphic features. Genetic tests revealed the following: 1) mixed gonadal dysgenesis - modifying treatment; 2) Fabry disease - enzyme treatment and rhGH improved growth; 3) Kallmann syndrome - discontinuing rhGH for testosterone supplementation; 4) KBG syndrome. Conclusions: 1. The presence of dysmorphic features and symptoms atypical for growth hormone deficiencies could warrant genetic diagnostics before initiating treatment. 2. Lack of significant improvement in growth is an indication for reevaluation of patients who have not completed growth. 3. Genetic studies in this patient group often elucidate the causes of slow growth rate. 4. The case authors have developed a proposal for a multicentre program aimed at establishing indications for genetic diagnosis in children diagnosed with SNP and SGA treated with rhGH. [ABSTRACT FROM AUTHOR]

Objective: Oncologic treatment can affect the adrenal glands, which in stressful situations may lead to life threatening adrenal crisis. The aim of the study was to assess adrenal function in pediatric acute lymphoblastic leukemia (ALL) survivors and to identify the best markers for this assessment. Methods: Forty-three ALL survivors, mean age 8.5±3.6 years and 45 age and sex-matched healthy controls were recruited to the study. ALL patients were assessed once within five years following oncological treatment completion. Fasting blood samples were collected from all participants to measure: fasting blood glucose (FBG); cortisol; aldosterone; plasma renin activity (PRA); dehydroepiandrostendionesulfate (DHEA-S); and adrenocorticotropic hormone (ACTH). Moreover, diurnal profile of cortisol levels and 24-hour urinary free cortisol (UFC) were assessed. ALL survivors underwent a test with 1 ug of synthetic ACTH. Results: The study revealed lower level of PRA (1.94±0.98 ng/mL/h vs 3.61±4.85 ng/mL/h, p=0.029) and higher FBG (4.6±0.38 mmol/L vs 4.41±0.39 mmol/L, p=0.018) in the ALL group compared to controls. UFC correlated with evening cortisol (p=0.015, r=0.26), midnight cortisol (p=0.002, r=0.33), and DHEA-S (p=0.004, r=0.32). UFC also correlated with systolic and diastolic blood pressure (p=0.033, r=0.23 and p=0.005, r=0.31, respectively). The ACTH test confirmed impaired adrenal function in 4/43 ALL survivors (9%). Two of the patients who needed permanent hydrocortisone replacement had low UFC, midnight cortisol and DHEA-S levels. Conclusion: These results highlight the importance of reviewing adrenal gland functionality after chemo/radiotherapy in ALL survivors. DHEA-S proved to be a good marker to assess the adrenal glands after oncological therapy. Post-treatment disturbances of the adrenal axis could be associated with metabolic complications. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate the clinical phenotypes of glucokinase-maturity-onset diabetes of the young (GCKMODY) pediatric patients from Southwest Poland and to search for phenotype-genotype correlations. Methods: We conducted a retrospective analysis of data on 37 CGK-MODY patients consisting of 21 girls and 16 boys of ages 1.9-20.1 (mean 12.5±5.2) years, treated in our centre in the time period between 2002 and 2013. Results: GCK-MODY carriers were found in a frequency of 3% among 1043 diabetes mellitus (DM) patients and constituted the second most numerous group of DM patients, following type 1 DM, in our centre. The mean age of GCK-MODY diagnosis was 10.4±4.5 years. The findings leading to the diagnosis were impaired fasting glucose (IFG) (15/37), symptoms of hyperglycemia (4/37), and a GCK-MODY family history (18/37). Mean fasting blood glucose level was 6.67±1.64 mmol/L. In the sample, there were patients with normal values (4/37), those with DM (10/37), and IFG (23/37). In OGTT, 120 min glucose level was normal in 8, diabetic in 2, and characteristic for glucose intolerance in 27 of the 37 cases. Twelve of the 37 cases (32%) were identified as GCK-MODY carriers. In the total group, mean C-peptide level was 2.13±0.65 ng/mL and HbA1c was 6.26±0.45% (44.9±-18 mmol/mol). Thirty-two patients had a family history of DM. DM autoantibodies were detected in two patients. The most common mutations were p.Gly318Arg (11/37) and p.Val302Leu (8/37). There was no correlation between type of mutations and plasma glucose levels. Conclusion: The phenotype of GCK-MODY patients may vary from those characteristic for other DM types to an asymptomatic state with normal FG with no correlation with genotype. [ABSTRACT FROM AUTHOR]

Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are known to be at risk of developing endocrine abnormalities, but occurrence of diabetes mellitus (DM) is a relatively recent observation. We present a 17.5-year-old girl with DM after high-dose radio- and chemotherapy followed by allogeneic HSCT for the treatment of acute lymphoblastic leukemia, diagnosed when she was 10 years old. In the posttransplantation period, multiple acute and chronic complications occurred. Among them, we observed graft versus host disease requiring corticosteroid therapy, pancreatitis and some endocrine complications like primary hypothyroidism, growth hormone deficiency and hypergonadotropic hypogonadism. DM with some components of metabolic syndrome-like insulin resistance, high arterial blood pressure and dyslipidemia developed during the first year after HSCT. Five years later, a trend towards increased requirement of insulin with deterioration in metabolic control of DM was observed, despite a normal level of C-peptide and negative diabetes autoantibodies. After the addition of metformin to continuous subcutaneous insulin infusion in the therapy of DM, an improvement in metabolic control was observed. Due to the possible mechanism of insulin resistance which is associated with impaired insulin receptors after HSCT procedure, metformin with insulin appears to be effective in the treatment of this type of diabetes. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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Among long-term survivors after hematopoietic stem cell transplantation (HSCT) late endocrine complications are observed in 20-50%. Very often these complications influence significantly the patient´s life and have to be treated till the end of life. Their proper prevention and monitoring are extremely important in patients who underwent HSCT during childhood. Since the 90s of the last millennium/century, thyroid dysfunction, disorders of somatic and sexual development, and disturbances of fertility have been presented in several publications. In the paper, less known endocrine complications after HSCT published in the last years are discussed. Disorders of carbohydrate metabolism, post-transplant diabetes and insulin resistance are presented. Moreover, dyslipidemia, hypertension, and post-transplant bone metabolic disease are demonstrated/shown. The paper describes the etiopathogenesis, methods of prevention as well as treatment and the results of the treatment of these endocrine complications after HSCT. Moreover, actual recommendations for screening and prevention of endocrine complications in long-term HCT survivors are presented.

Since the 1980s, hematopoietic stem cell transplantation (HSCT) has been performed for malignant and non-malignant disorders leading to increasing numbers of long-term survivors. Some of them develop long-term posttransplantation complications, among them endocrine complications that arise many years after HSCT and demand to be treated till the end of patients´ life. In the paper "classical", observed several years after HSCT had been used as a treatment procedure, endocrine complications are discussed and the review of literature regarding this problem is presented. Thyroid dysfunction, disorders of somatic and sexual development are presented in details. Gonad dysfunction with the problem of fertility disturbances is reported. The paper presents the etiopathogenesis, methods of prevention, as well as treatment and the results of the treatment of these endocrine complications after HSCT. Moreover actual recommendations for screening and prevention of endocrine complications in long-term HCT survivors are presented.

Introduction: Craniopharyngioma can cause neurological, ophthalmological and endocrine signs and symptoms., Aim of the Study: Retrospective analysis of symptoms accompanying diagnosis of craniopharyngioma in children., Material and Methods: 10 children and adolescents, 3.75-14.08 years old, median 8.96, treated in our centre in the years 1992-2010, with diagnosis of craniopharyngioma, were included into the study. In the analysis clinical symptoms at the moment of diagnosis, before surgery treatment were taken into consideration. Data from medical histories, physical examination, auxological data, biochemical and hormonal parameters were analyzed., Results: Among 10 patients, 9 had headaches, 4 had experienced vomiting, 2 had symptoms of cranial hypertension, 6 had vision disorders, 8 had endocrine disorders. A decrease of growth rate was observed in 5 children (among 7 with previous anthropometric data), diabetes insipidus in 2, gain of body weight and delayed puberty in 1, and secondary hypothyroidism in 1 patient. Endocrine disorders appeared on average 13 months before diagnosis of craniopharyngioma. Among them the earliest was the decrease of growth rate - on average 23 months before the diagnosis, and the latest diabetes insipidus - 2 months before it. The most frequent symptom - headaches appeared 2 months before the diagnosis., Conclusions: 1. Endocrine symptoms are early symptoms of craniopharyngioma, which usually appear before neurological, and ophthalmological disorders. 2. Craniopharyngioma may be a cause of growth disorders in children and adolescents, therefore a detailed analysis of height data on growth charts in pediatric patients is very important for the diagnosis.