Endocrine Abstracts

Introduction: Adrenocortical carcinoma (ACC) has a poor prognosis and limited therapeutic options. The epidermal growth factor receptor (EGFR) expression was found to be a good discriminator between malignant and benign adrenal tumours, but was mutated only in 3–10% of ACC cases.Aim: The aim of this study was to assess the effect of inhibition of EGFR with targeted therapies, i.e. Erlotinib (with and without EGF stimulation) on ACC cell proliferatio...

Background: In patients with phaeochromocytoma, sudden and/or chronic exposure to catecholamines may predispose to cardiac pathology, including left ventricular (LV) hypertrophy, myocardial infarction, stress-induced cardiomyopathy and heart failure. We conducted the first prospective, multicentre study using cardiovascular magnetic resonance (CMR) imaging to describe the variety and incidence of cardiac abnormalities in phaeochromocytoma.Methods: Fifty ...

The islet-enriched transcription factor MAFA regulates the expression of genes critical to beta cell function and insulin secretion. We previously described anovel MAFA mutation (c.191C > T, p.S64F) causing familial insulinomatosis and diabetes mellitus, with male carriers more often developing diabetes and females more prone to insulinomatosis. The exact molecular mechanisms underlying these phenotypes are unclear. In this study, we assessed glucose metabolism an...

Introduction: Germline AIP and MEN1 mutations are the main known aetiologies of familial pituitary neuroendocrine tumours (PitNETs), which represent 5% of all PitNETs. We compared the clinical and tumour characteristics of AIP (AIP mut) and MEN1 mutation-positive (MEN1 mut) PitNET patients.Methods: We retrospectively analysed 70 MEN1 mut and 167 AIP mut patients with PitNETs. MEN...

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 ...

AIP mutations predispose to familial isolated pituitary adenomas (FIPA) and 45 different AIP mutations have been described in the literature. Most of these mutations result in complete disruption of the C-terminal region of the AIP protein due to early stop codons. In this study we were particularly interested in the effect of AIP mutations in the promoter region (−270−−269CG & −220C) and 2 synonymous mutations (c.249G>T, p.G83= and c...

Ghrelin, cannabinoids and glucocorticoids have all orexigenic and widespread metabolic effects. AMPK is a major controller of many metabolic processes. We have studied the effects of ghrelin and glucocorticoids and their interaction with endocannabinoids using cannabinoid-receptor-1 (CB1) knock-out mice and CB1 antagonist-treated mice, and using tissue samples from patients with Cushing’s syndrome and from a rodent model of Cushing’s syndrome. AMPK activity and downs...

Mutations in AIP have been identified in a significant proportion of families with pituitary adenomas, most commonly in familial acromegaly. However, no data are available about the pituitary expression of AIP and how lack of AIP is involved in tumorigenesis.We identified 10 kindreds with AIP mutations out of 31 families. We studied RNA and protein expression of AIP in normal as well as familial and sporadic pituitary adenomas. In the normal pituitary st...

Background: Excess glucocorticoids result in Cushing’s syndrome (CS) which is characterised by increased food intake, central obesity, dyslipidaemia and insulin resistance, leading to the metabolic syndrome. AMPK is a regulator of energy homeostasis and plays an important role in the regulation of appetite, glucose uptake, lipogenesis and gluconeogenesis. We hypothesised that the effects of corticosteroids on metabolism would be mediated by changes in AMPK activity in a t...

This abstract was printed as a duplication of abstract P291 and corrected onlineBackground: Excess glucocorticoids result in Cushing’s syndrome (CS) which is characterised by increased food intake, central obesity, dyslipidaemia and insulin resistance, leading to the metabolic syndrome. AMPK is a regulator of energy homeostasis and plays an important role in the regulation of appetite, glucose uptake, lipogenesis and gluconeogenesis. We hypothesised...