Endocrine Abstracts

Acromegaly is associated with increased morbidity and mortality. There are several treatment options for acromegaly including surgery, radiotherapy and medical therapy. The aims of treatment in patients with acromegaly is to achieve GH and IGF-I concentrations associated with cure or normalisation of mortality.We examined predictive factors of response to treatment with dopamine agonists (DA) and somatostatin analogues (SSA) in a cohort of 501 patients w...

Acromegaly is associated with increased morbidity and premature mortality which has been demonstrated in a number of retrospective studies reporting a standardised mortality ratio (SMR) between 1.3 and 3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or surgery and/or radiotherapy. Hypopituitarism is also associated with an increased SMR (1.2–2.17).Using the West Midlands Acromegaly database (n<...

Inherited growth hormone insensitivity (GHI) is usually caused by mutations in the GH receptor (GHR). Patients present with short stature associated with a mid-facial hypoplasia (Laron facial features) or with normal facial appearance. We previously described an intronic mutation in the GHR gene (A−1 to G−1 substitution in intron 6) resulting in the activation of a pseudoexon (6Ψ) in four related GHI patients with normal facial fea...

3M syndrome is characterised by severe intra-uterine and post-natal growth failure. Patients have a characteristic triangular facial appearance and disproportionate short stature with tall vertebral bodies and over-tubulation of long bones. The condition bears some resemblance to the Russell Silver syndrome, but is transmitted as an autosomal recessive trait. It has been proposed that heterozygous carriers demonstrate mild phenotypic manifestations of the condition.<p clas...

Hyperinsulinism in Infancy (HI) is the most common cause of recurrent or persistent hypoglycaemia in early childhood, and manifests as either diffuse abnormalities of pancreatic beta-cell function (Di-HI), or focal adenomatous hyperplasia of beta-cells (Fo-HI). Di-HI is caused by defects in KATP channel genes ABCC8 (SUR1) or KCNJ11 (Kir6.2). Fo-HI arises from somatic loss of maternal heterozygosity resulting in the expression of paternally-derived mutation(s) in SUR1 or Kir6.2...

Background: Following IHC of CALR, H-scoring was performed by a pathologist. H-scoring was validated by MIF of the same tissue, wherein random-forest machine learning (ML) classifiers were employed to classify cells. ML classifiers were trained to distinguish between pNET cells and tumor stroma using approximately 30% of cells for the respective cell population of interest in each TMA core. Pearson’s correlations were used to evaluate the relationship between H-scoring an...

Background: The optimal management of paediatric craniopharyngiomas has been debated for years. Radical surgery aimed at complete resection (CR) was the approach for several decades, with higher reported rates of tumour control compared with incomplete resection (IR). The shift towards conservative surgery with adjuvant radiotherapy (DXT), aimed at reducing post-operative morbidities, especially hypothalamic and visual, has not been systematically studied.<p class="abstext...

Introduction: Congenital hyperinsulinism (CHI) is a cause of severe hypoglycaemia due to insulin over-secretion. The medical management of CHI involves supplementary glucose, which combined with insulin excess, may be obesogenic. However, increased weight in CHI patients has not been reported. We have investigated if children with CHI increase in weight and if genetic or treatment factors influence the weight trajectory.Methods: Weights were measured and...

Introduction: Congenital hyperinsulinism (CHI) causes severe hypoglycaemia, which can be either focal or diffuse in aetiology. Both forms are associated with paternally inherited mutations in ABCC8/KCNJ11. Lymphocytic DNA analysis alone is inadequate to diagnose focal CHI, as pancreatic maternal allelic silencing cannot be tested prior to surgery. Additional 18-fluorodopa PET–CT scanning (PET–CT) is required for definitive diagnosis; in this study, ...

Introduction: Congenital hyperinsulinism (CHI) may arise due to loss-of-function mutations in ABCC8 and KCNJ11 genes which encode subunits of ATP-sensitive potassium (KATP) channels. KATP channels couple nutrient metabolism with insulin secretion in pancreatic β-cells but are also located in enteroendocrine L- and K-cells and may play a role in the control of GLP-1 and GIP secretion respectively. More than 70% of patients with CHI h...