Dilation of the ascending aorta in Turner syndrome - a prospective cardiovascular magnetic resonance study

<p>Abstract</p> <p>Background</p> <p>The risk of aortic dissection is 100-fold increased in Turner syndrome (TS). Unfortunately, risk stratification is inadequate due to a lack of insight into the natural course of the syndrome-associated aortopathy. Therefore, this study aimed to prospectively assess aortic dimensions in TS.</p> <p>Methods</p> <p>Eighty adult TS patients were examined twice with a mean follow-up of 2.4 ± 0.4 years, and 67 healthy age and gender-matched controls were examined once. Aortic dimensions were measured at nine predefined positions using 3D, non-contrast and free-breathing cardiovascular magnetic resonance. Transthoracic echocardiography and 24-hour ambulatory blood pressure were also performed.</p> <p>Results</p> <p>At baseline, aortic diameters (body surface area indexed) were larger at all positions in TS. Aortic dilation was more prevalent at all positions excluding the distal transverse aortic arch. Aortic diameter increased in the aortic sinus, at the sinotubular junction and in the mid-ascending aorta with growth rates of 0.1 - 0.4 mm/year. Aortic diameters at all other positions were unchanged. The bicuspid aortic valve conferred higher aortic sinus growth rates (p < 0.05). No other predictors of aortic growth were identified.</p> <p>Conclusion</p> <p>A general aortopathy is present in TS with enlargement of the ascending aorta, which is accelerated in the presence of a bicuspid aortic valve.</p

Delayed β-cell response and glucose intolerance in young women with Turner syndrome

<p>Abstract</p> <p>Background</p> <p>To investigate glucose homeostasis in detail in Turner syndrome (TS), where impaired glucose tolerance (IGT) and type 2 diabetes are frequent.</p> <p>Methods</p> <p>Cross sectional study of women with Turner syndrome (TS)(n = 13) and age and body mass index matched controls (C) (n = 13), evaluated by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic, euglycemic clamp), beta-cell function (hyperglycaemic clamp, arginine and GLP-1 stimulation) and insulin pulsatility.</p> <p>Results</p> <p>Fasting glucose and insulin levels were similar. Higher glucose responses was seen in TS during OGTT and IVGTT, persisting after correction for body weight or muscle mass, while insulin responses were similar in TS and C, despite the higher glucose level in TS, leading to an insufficient increase in insulin response during dynamic testing. Insulin sensitivity was comparable in the two groups (TS vs. control: 8.6 ± 1.8 vs. 8.9 ± 1.8 mg/kg*30 min; p = 0.6), and the insulin responses to dynamic β-cell function tests were similar. Insulin secretion patterns examined by deconvolution analysis, approximate entropy, spectral analysis and autocorrelation analysis were similar. In addition we found low IGF-I, higher levels of cortisol and norepinephrine and an increased waist-hip ratio in TS.</p> <p>Conclusions</p> <p>Young normal weight TS women show significant glucose intolerance in spite of normal insulin secretion during hyperglycaemic clamping and normal insulin sensitivity. We recommend regularly testing for diabetes in TS.</p> <p>Trial Registration</p> <p>Registered with <url>http://clinicaltrials.com</url>, ID nr: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00419107">NCT00419107</a></p

GH safety workshop position paper: A critical appraisal of recombinant human GH therapy in children and adults

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-Term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-Term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement

An overview of concepts and approaches used in estimating the burden of congenital disorders globally.

Congenital disorders are an important cause of pregnancy loss, premature death and life-long disability. A range of interventions can greatly reduce their burden, but the absence of local epidemiological data on their prevalence and the impact of interventions impede policy and service development in many countries. In an attempt to overcome these deficiencies, we have developed a tool-The Modell Global Database of Congenital Disorders (MGDb) that combines general biological principles and available observational data with demographic data, to generate estimates of the birth prevalence and effects of interventions on mortality and disability due to congenital disorders. MGDb aims to support policy development by generating country, regional and global epidemiological estimates. Here we provide an overview of the concepts and methodological approach used to develop MGDb