A 52-week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity.

OBJECTIVE: Hypothalamic obesity (HO) is a common complication of hypothalamic tumors, and effective therapies are lacking. The objective of this pilot study was to investigate changes in body weight before and during treatment with exenatide. METHODS: This was a prospective, open-label, 52-week pilot study of exenatide (10 mcg b.i.d.) in adults with HO. Ten patients enrolled, and eight completed the study. Study measures included indirect calorimetry, body composition, buffet meals, diet recall, actigraphy, and hormone assays. RESULTS: Participants had obesity with a baseline weight of 137.2 ± 37.6 kg. Exenatide therapy was well tolerated. Change in weight with exenatide therapy was not significant (-1.4 ± 4.3 kg [95% CI -4.9 to 2.2], P = 0.40), but six out of eight completers lost weight (-6.2 to -0.2 kg). Participants reported significantly lower intake on food recall during treatment compared with baseline (7837.8 ± 2796.6 vs. 6258.4 ± 1970.7 kJ [95% CI -2915.8 to -242.6], P = 0.027), but there was no change in intake during buffet meals. CONCLUSIONS: Significant weight loss was not observed in patients with HO treated with exenatide, but 75% of completers had stable or decreasing weight. Further studies are needed to evaluate weight loss efficacy in patients with HO.

Delayed diagnosis of hypothyroidism following excision of a thyroglossal duct cyst.

Thyroglossal duct cysts can contain ectopic thyroid tissue, and in some cases this tissue may be the only functional thyroid gland. We present the case of a 6-year-old girl with delayed diagnosis of iatrogenic hypothyroidism that developed after excision of a thyroglossal duct cyst.

Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice.

Obesity triggers a low-grade systemic inflammation, which plays an important role in the development of obesity-associated metabolic diseases. In searching for links between lipid accumulation and chronic inflammation, we examined invariant natural killer T (iNKT) cells, a subset of T lymphocytes that react with lipids and regulate inflammatory responses. We show that iNKT cells respond to dietary lipid excess and become activated before or at the time of tissue recruitment of inflammatory leukocytes, and that these cells progressively increase proinflammatory cytokine production in obese mice. Such iNKT cells skew other leukocytes toward proinflammatory cytokine production and induce an imbalanced proinflammatory cytokine environment in multiple tissues. Further, iNKT cell deficiency ameliorates tissue inflammation and provides protection against obesity-induced insulin resistance and hepatic steatosis. Conversely, chronic iNKT cell stimulation using a canonical iNKT cell agonist exacerbates tissue inflammation and obesity-associated metabolic disease. These findings place iNKT cells into the complex network linking lipid excess to inflammation in obesity and suggest new therapeutic avenues for obesity-associated metabolic disorders.

Glucagon-like peptide 1 and pancreatic polypeptide responses to feeding in normal weight and overweight children.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) are intestinal hormones that are involved in the post-prandial satiety response. We sought to assess meal-related changes in these hormones in young children and determine whether differences exist between normal weight (NW) and overweight (OW) children. METHODS: Seven to 11-year-old healthy NW (n=20) and OW (n=12) volunteers were given a standardized breakfast and lunch following an overnight fast and had measurements of GLP-1 and PP over 9 hours. We characterized whether GLP-1 and PP changed from the pre-prandial to the post-prandial state and whether the serum levels corresponded to reported appetite. RESULTS: GLP-1 did not increase after eating, did not decline prior to the next meal, and did not correspond to satiety ratings in either group. PP increased post-prandially in OW children after both breakfast and lunch, but in the NW group PP only increased after breakfast. PP levels did not decline in either group as the next meal approached. CONCLUSIONS: In our study of school-age children, feeding had little effect on GLP-1 secretion and a variable effect on serum PP levels. Observed differences in the GLP-1 and PP responses between the NW and OW groups do not suggest there is an intrinsic abnormality in their secretion that causes weight gain.

Prevalence of adrenal insufficiency following systemic glucocorticoid therapy in infants with hemangiomas.

OBJECTIVE: To determine the prevalence of adrenal insufficiency in infants with hemangiomas following treatment with systemic glucocorticoids (GCs). DESIGN: Prospective study for 18 months. SETTING: Hemangioma and vascular malformation center at a tertiary care children's hospital. PATIENTS: Sixteen infants with hemangiomas had an adrenal axis evaluation as soon as possible following the completion of GC therapy. Ten healthy control infants were also evaluated for comparison. INTERVENTIONS: Prednisolone at a starting dose of 2 to 3 mg/kg/d for 4 weeks, followed by a tapering period. The mean duration of GC treatment was 7.2 months. MAIN OUTCOME MEASURE: Prevalence of adrenal insufficiency in GC-treated subjects as assessed by a combination low-dose/high-dose corticotropin stimulation test. RESULTS: Subjects underwent corticotropin testing at a mean of 13 days after the completion of therapy. Only 1 of the 16 GC-treated infants (6%) had adrenal insufficiency. This subject was tested 1 day after GC treatment was stopped, and results from retesting 3 months later were normal. All control subjects had normal adrenal function. CONCLUSION: Infants with hemangiomas are at low risk of adrenal insufficiency following the completion of GC therapy, as used in our hemangioma center.

Transcription factor FOXF1 regulates growth hormone variant gene expression.

Deletion analysis of the human growth hormone variant (GHV) promoter in transient transfection studies in BeWo choriocarcinoma and HepG2 cells indicated that the region extending from nt -158/+57 retained full transcriptional activity. DNase I footprint analysis of the fragment revealed a protected region at nt -82/-77, which is in a putative FOXF1/FOXF2 binding site. Supershift assays using an antiserum to human FOXF1 demonstrated that the protected region binds FOXF1. Overexpression of FOXF1 in BeWo and HepG2 cells induced the GHV promoter, whereas overexpression of FOXF2 was without effect. Mutagenesis of the FOXF1/FOXF2 site reduced basal promoter activity by 50-60% and markedly attenuated transactivation of the promoter by FOXF1. These studies indicate that FOXF1 induces GHV expression by interaction with a FOXF1/FOXF2 cis-element in the proximal promoter.

Growth, bone mineral accretion, and adrenal function in glucocorticoid-treated infants with hemangiomas-- a retrospective study.

Hemangiomas, common proliferative vascular tumors, can grow rapidly in the first months of life. Although therapy with high-dose oral glucocorticoids is standard for lesions that threaten vital functions or are disfiguring, little is known about the endocrine consequences of this treatment. Using retrospective data, we examined growth velocity, changes in bone mineral density, and adrenal function in infants with hemangiomas treated with systemic glucocorticoids. Treatment consisted of oral prednisolone 2 to 4 mg/kg/day or dexamethasone 1 mg/kg/day. Mean growth velocity Z score on glucocorticoid therapy was -1.41 standard deviations in 13 patients. In four infants with adequate follow-up, growth velocity increased to +1.90 standard deviations after glucocorticoid treatment (Delta growth velocity +3.31 standard deviations). Mean lumbar spine bone mineral density Z score was -2.46 standard deviations before glucocorticoid treatment and -1.08 standard deviations at the end of treatment in six infants. Adrenal function after glucocorticoid therapy was assessed by low-dose adrenocorticotropic hormone stimulation test in 10 infants. Eight had a normal cortisol response, and one had a borderline response. One infant, who had been treated with dexamethasone, had an abnormal test result. In conclusion, systemic glucocorticoid treatment in infants with hemangiomas slowed linear growth, but "catch-up" growth was observed after treatment ceased. Glucocorticoids did not affect bone mineralization adversely. Only 1 of 10 glucocorticoid-treated infants had clear evidence of adrenal insufficiency after therapy was stopped.

Autoimmune thyroiditis in 18q deletion syndrome.

Deletion of a segment of the long arm of chromosome 18 causes characteristic physical features and mental retardation. Autoimmune disorders have been described with this syndrome in a limited number of reports. We describe 2 cases of autoimmune hypothyroidism in children with 18q deletion syndrome.