Endocrine Abstracts

Background: Although MRI remains the investigation of choice for pituitary imaging, it does not provide information about the ‘functionality’ of lesions (e.g. residual adenoma vs post-surgical scar tissue), and cannot reliably identify all microadenomas. These limitations are of particular relevance in acromegaly where clinical and biochemical evidence of disease activity mandates (further) treatment.Methods: We hypothesised that i) imaging wit...

Nineteen cases of insulinoma were treated in this centre between 2003 and 2012 (12 female, 7 male, 5 associated with MEN-1). Of the cohort, 14 had their primary investigation and management here. All presented with symptoms consistent with hypoglycaemia and had a supervised fast demonstrating serum glucose <2.2 mmol/l with inappropriately normal/elevated insulin.11 of 14 patients proceeded to surgery. Two elderly patients declined further investigati...

Acromegaly causes a distinct cardiomyopathy. Growth hormone deficiency (GHD) limits cardiac response to exercise and increases cardiac mortality. Cardiac magnetic resonance imaging (CMR) is considered the gold standard for assessment of cardiac mass and provides data on function, fibrosis, valves and ischaemia. Twenty-three patients with abnormal GH levels (acromegaly, n=13; adult-onset GHD, n=10) and 23 matched controls underwent CMR. Patients had repeat CMR at ...

Seventeen newly-diagnosed acromegalic patients (8 female, 9 male: mean age 55 year, range 26–73 year) were recruited to the A.C.R.O.P.A.T. trial. Patients were assessed prior to, and following, 6 months of treatment with Somatuline Autogel® (SA).Growth hormone (GH) & insulin-like growth factor 1 (IGF1): Following treatment, GH and IGF1 levels fell significantly in all but one subject: median GH change −17.23 mU/l (interquar...

Respiratory disorders are a major cause of illness and impaired physical function in patients with acromegaly, contributing to 25% of all recorded deaths, with respiratory mortality 3-fold higher than in normal subjects. Sleep apnoea (SA), the phenomenon of recurrent cessation or decrease of airflow to the lungs during sleep, is the commonest reported respiratory complication. Both obstructive (OSA) and central (CSA) sleep apnoeas are known to occur, although the overall preva...

RP (a 60 yr-old male) was found to have multiple atrial myxomata, whilst being investigated for recurrent attacks of amaurosis fugax affecting his left eye. During the preceding twenty years he had undergone repeated resections of cutaneous tumours, which were reported as neurofibromata. A clinical diagnosis of Carney Complex (CNC) was made based on the presence of multiple cutaneous nodules and atrial myxomata. RP displayed mild acromegalic features, but no pigmentation abnor...

The nuclear receptor PPARgamma is important for biological processes including adipogenesis and glucose homeostasis. In subjects with severe insulin resistance, we have previously reported two types of human PPARgamma gene defect: heterozygous, missense mutations (P467L, V290M) in the ligand binding domain (LBD) which inhibit wild type (WT) receptor action in a dominant negative manner by recruitment of transcriptional corepressors; or double heterozygosity for a frameshift/pr...

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. Gain-of-function mutations in both CTNNB1 and the G-protein coupled receptor GNA11 were found by whole exome sequencing in 3/10 APAs. Further sequencing of...

Background: Primary aldosteronism (PA) is the leading, potentially reversible, cause of secondary hypertension. For most patients in whom surgery is being considered, adrenal vein sampling (AVS) is recommended to distinguish unilateral and bilateral causes. However, AVS remains technically challenging, and a significant proportion of patients are unable to progress to surgery because AVS is unavailable or unsuccessful. We have explored whether [11C]Metomidate PET/CT...

X-linked IGSF1 (immunoglobulin superfamily, member 1) loss-of-function mutations in males are associated with central hypothyroidism, macroorchidism, and a variable spectrum of anterior pituitary dysfunction. Igsf1 deficient male mice also exhibit central hypothyroidism, however, the physiological and molecular function of IGSF1 in both species has not yet been elucidated. Although partial transient GH deficiency is a ra...