Metabolic features and changes in glucose-induced serum glucagon-like peptide-1 levels in children with hypothalamic obesity.

Background Hypothalamic damage may alter glucagon-like peptide-1 (GLP-1) secretion and be involved in the pathogenesis of obesity. We aim to evaluate the metabolic features and the dynamic changes of GLP-1 levels during an oral glucose tolerance test (OGTT) in children with hypothalamic obesity (HO) compared with simple obesity controls. Methods Subjects included eight patients (six females, aged 9-16 years) with hypothalamo-pituitary tumors who later developed obesity and eight controls with simple obesity matched for age, body mass index (BMI), gender and puberty. We assessed the metabolic syndrome features, fat mass, severity of hyperphagia using a standardized questionnaire, and measured glucose, insulin and GLP-1 levels during a standard 75 g OGTT. Results Age, gender distribution, pubertal status and BMI-Z scores were not significantly different. Subjects with HO had higher fasting triglycerides (TG) than controls (128 vs. 94 mg/dL; p=0.05). Four HO subjects and three controls met the criteria for the metabolic syndrome. Fasting and 120 min post-glucose load GLP-1 levels were significantly higher in HO patients than in controls (21.9 vs. 19.7 pg/mL; p=0.025, 22.1 vs. 17.7 pg/mL; p=0.012). Patients with HO had significantly higher hyperphagia scores than in simple obese controls (13 vs. 2.5; p=0.012). Conclusions Patients with HO appear to have more metabolic complications and hyperphagia than controls with simple obesity. Impaired satiety may play an important role in HO. Fasting and glucose-induced serum GLP-1 concentrations seem to be altered in HO patients and could be a part of the pathogenesis of HO.

DKA with Severe Hypertriglyceridemia and Cerebral Edema in an Adolescent Boy: A Case Study and Review of the Literature.

A 13-year-old adolescent boy with type 1 diabetes mellitus (1b) presented with diabetic ketoacidosis (DKA) and cerebral edema. Grossly lipemic serum and lipemia retinals due to extremely high triglyceride (TG) level were observed without evidence of xanthoma or xanthelasma. Cerebral edema was treated by appropriate ventilation and mannitol administration. Normal saline was carefully given and regular insulin was titrated according to blood sugar levels. Triglyceride levels were reduced from 9,800 mg/dL to normal range within 9 days after conventional treatment was commenced without antilipid medication. Based on our review of the literature, this is the first reported case of confirmed pediatric DKA with severe hypertriglyceridemia and cerebral edema. In patients with DKA and hypertriglyceridemia, clinicians should be mindful of the possibility of associated acute pancreatitis and cerebral edema.

Germline and somatic DICER1 mutations in a pituitary blastoma causing infantile-onset Cushing's disease.

CONTEXT: Pituitary blastoma causing Cushing's syndrome in infancy is very rare, and its molecular pathomechanism is not well understood. OBJECTIVE: Our objective was to identify genetic changes of a pituitary blastoma causing infantile-onset Cushing's syndrome in a Thai girl without a family history of cancers. METHODS: Genomic DNA from both leukocytes and tumor tissues was used for whole-exome sequencing (WES) and Sanger sequencing of DICER1. The cDNA reverse-transcribed from RNA extracted from both leukocytes and tumor tissues was used for Sanger sequencing, quantitative real-time PCR (qRT-PCR), and pyrosequencing of DICER1. RESULTS: WES of leukocytes identified a novel heterozygous c.3046delA (p.S1016VfsX1065) mutation in the DICER1 gene. WES of the tumor tissues detected the same frameshift germline mutation and another novel somatic missense c.5438A→T (p.E1813V) mutation. Both mutations were validated by Sanger sequencing. Quantitative real-time PCR revealed that the DICER1 mRNA levels of the tumor tissues were 54% compared with those of her leukocytes. Pyrosequencing showed that the deletion allele constituted 12% and 0% of the DICER1 cDNA of the proband's leukocytes and tumor tissues, respectively. CONCLUSION: Our study extends the phenotypic and mutational spectrum of DICER1 mutations to include infantile-onset Cushing's disease and 2 novel mutations. Loss of function of both DICER1 alleles appears to be crucial to initiate tumor development.

Obesity, metabolic syndrome, and insulin dynamics in children after craniopharyngioma surgery.

INTRODUCTION: Children after craniopharyngioma surgery often develop rapid weight gain and hyperphagia. We investigate the metabolic syndrome features, risk factors, and the insulin dynamics in these patients. MATERIALS AND METHODS: Standard oral glucose tolerance tests (OGTT) were performed in 12 subjects, aged 7.7-18.1 years, after surgical removal of craniopharyngioma and their healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Blood samples were obtained for measurement of levels of plasma glucose, insulin, lipids, liver enzymes, baseline hormonal profiles with calculation of insulin secretion, and insulin sensitivity indices derived from OGTT. RESULTS AND DISCUSSION: Nine of 12 subjects were severely obese. All patients exhibited significant weight gain after surgery. The waist to hip ratio was higher in subjects compared to controls (P = 0.023). Subjects had higher fasting triglycerides (P = 0.019) and lower HDL/total cholesterol ratio (P = 0.012). Five of 12 subjects met the criteria for the metabolic syndrome, compared with one of 12 in controls. One patient had prediabetes and another patient had overt type 2 diabetes. Six of 12 subjects had nonalcoholic steatohepatitis. No significant risk factors were found between each group of patients with and without the metabolic syndrome. There were no differences of insulin secretion and insulin sensitivity indices between craniopharyngioma and control subjects. CONCLUSION: Children after craniopharyngioma surgery are at risk of rapid weight gain and the development of metabolic syndrome. Further studies to better understand the mechanism are required to design effective treatment and prevention.