Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement

OBJECTIVE: Many patients treated for craniopharyngioma (CP) complain of a relative incapacity for physical activity. Whether this is due to an objective decrease in adaptation to exercise is unclear. We assessed exercise tolerance in children with surgically treated CP and appropriate pituitary hormone replacement therapy compared with healthy controls and we examined the potential relationships with hypothalamic involvement, GH replacement, and the catecholamine deficiency frequently observed in these subjects. DESIGN AND METHODS: Seventeen subjects (12 males and five females) with CP and 22 healthy controls (14 males and eight females) aged 15.3+/-2.5 years (7.3-18 years) underwent a standardized cycle ergometer test. Maximum aerobic capacity was expressed as the ratio of VO(2max) to fat-free mass (VO(2max)/FFM), a measure independent of age and fat mass in children. RESULTS: VO(2max)/FFM was 20% lower in children with CP compared with controls (P<0.05), even after adjustment for gender. Children with hypothalamic involvement (n=10) had a higher percentage of fat mass (P<0.05) than those without hypothalamic involvement (n=7) and lower VO(2max)/FFM (P<0.05), whereas children without hypothalamic involvement had VO(2max)/FFM close to that of controls (P>0.05). GH treatment was associated with a significant positive effect on aerobic capacity (P<0.05) only in the absence of hypothalamic involvement. No relationship was found between exercise capacity parameters and daily urine epinephrine excretion or epinephrine peak response to insulin-induced hypoglycemia. CONCLUSIONS: Children with CP have a decrease in aerobic capacity mainly related to hypothalamic involvement. The hypothalamic factors altering aerobic capacity remain to be determined

TRα Mutations in Human

Resistance to thyroid hormone alpha is an emerging syndrome, with up to now a limited number of published cases. Some features are common to most of the patients, but there is still some work to provide a comprehensive description of the full spectrum of the syndrome. A survey of the strategy to screen for and characterize the mutations in TR α gene is given

Laparoscopic adjustable gastric banding in adolescents: Results at two years including psychosocial aspects

BACKGROUND/PURPOSE: Obesity now affects 3%-4% of the pediatric population and contributes to the increase in cardiac mortality in adulthood. Bariatric surgery is the best treatment for weight loss and the obesity-associated comorbidities in adults. We report here our experience of laparoscopic adjustable gastric banding (LAGB) in adolescents. METHODS: The medical charts of the first 16 patients operated on in our center were reviewed. Data were compiled concerning weight loss, physical and biological comorbidities, health-related quality of life (QOL) and surgical complications before surgery and during 24months of follow-up. RESULTS: The maximal pre-operative median body mass index was 43.0kg·m(-2), decreasing to 33.0kg·m(-2) at 2years post-LAGB, which corresponded to a 49.2% excess body weight loss (p<0.001). Most comorbidities (glucose intolerance, hypertension and sleep apnea) resolved within the first year post-LAGB and QOL was improved on the PedsQL™ scales. No severe surgical complications were noted, with only three re-interventions for device failure (2) or band removal (1). CONCLUSION: LAGB is well tolerated in adolescents and shows a beneficial impact on weight loss and obesity-related comorbidities. Associated with global management, it may have a positive impact on patients\u27 QOL and social and psychological status

A new case of pcsk1 pathogenic variant with congenital proprotein convertase 1/3 deficiency and literature review

Issue: To report a homozygous pathogenic variant in PCSK1 in a boy affected with proprotein convertase 1/3 (PC1/3) deficiency. Case description and literature review: A male infant born to consanguineous Turkish parents presented in the first week of life with transient central diabetes insipidus, watery diarrhea, micropenis due to hypogonadotropic hypogonadism and GH deficiency, and transient asymptomatic hypoglycemia. Further endocrine defects gradually appeared, including central hypothyroidism and mild central hypocortisolism (at 1 yr), central diabetes insipidus that reappeared progressively (at 2.5 yr), and obesity (at 2 yr). Whole exome sequencing revealed a homozygous nonsense pathogenic variant (NM_000439.4) c. 595 C>T in exon 5 of PCSK1, not yet reported in cases of proprotein convertase 1/3 (PC1/3) deficiency. To date, 26 cases of PC1/3 deficiency have been reported in the literature. All individuals had early and severe malabsorptive diarrhea and 83% had polyuria-polydipsia syndrome (before 5 yr). Most (79%) had early-onset obesity. Various endocrine disorders were present, including growth hormone deficiency (44%), mild central hypothyroidism (56%), central hypogonadism (44%), central hypocortisolism (57%), and postprandial hypoglycemia (52%). When described (n=15), proinsulin levels were consistently high: between 8 and 154 times the upper limit of normal (mean 74). Conclusion: We described a homozygous nonsense pathogenic variant (NM_000439.4) c. 595 C>T in exon 5 of PCSK1 in a boy with congenital proprotein convertase 1/3 deficiency. Elevated proinsulin could be useful in the diagnosis of this condition

Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents

<p>Abstract</p> <p>Background</p> <p>Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents.</p> <p>Methods</p> <p>An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated.</p> <p>Results</p> <p>Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors.</p> <p>Conclusions</p> <p>Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.</p

Closed-loop driven by control-to-range algorithm outperforms threshold-low-glucose-suspend insulin delivery on glucose control albeit not on nocturnal hypoglycaemia in prepubertal patients with type 1 diabetes in a supervised hotel setting

This randomized control trial investigated glucose control with closed-loop (CL) versus threshold-low-glucose-suspend (TLGS) insulin pump delivery in pre-pubertal children with type 1 diabetes in supervised hotel conditions. The patients [n = 24, age range: 7-12, HbA1c: 7.5 ± 0.5% (58 ± 5 mmol/mol)] and their parents were admitted twice at a 3-week interval. CL control to range or TLGS set at 3.9 mmoL/L were assessed for 48 hour in randomized order. Admissions included three meals and one snack, and physical exercise. Meal boluses followed individual insulin/carb ratios. While overnight (22:00-08:00) per cent continuous glucose monitoring (CGM) time below 3.9 mmol/L (primary outcome) was similar, time in ranges 3.9 to 10.0 and 3.9 to 7.8 mmoL/L and mean CGM were all significantly improved with CL (P &lt; 0.001). These results were confirmed over the whole 48 hour. Disconnections between devices and limited accuracy of glucose sensors in the hypoglycaemic range appeared as limiting factors for optimal control. CL mode was well accepted while fear of hypoglycaemia was unchanged. CL did not minimize nocturnal hypoglycaemia exposure but improved time in target range compared to TLGS. Although safe and well-accepted, CL systems would benefit from more integrated devices