Endocrine Abstracts

Adrenocortical carcinomas (ACCs) are rare endocrine tumors with poor prognosis. They overexpress the insulin-like growth factor 2 (IGF2), that drives a proliferative autocrine loop by binding to IGF1R and IR. The majority of studies focused on IGF1R as mediator of IGF2 biological effects, but recently a high expression of IR, in particular of the isoform A, was observed in most ACCs, suggesting a potential role of this receptor in modulating IGF2 effects in adrenocortical tumo...

Background and aim: Obesity is a chronic disease associated with a positive energy balance leading to lipotoxicity, which contributes to the onset of obesity-associated metabolic disorders such as type 2 diabetes and insulin resistance. It’s well known that thermogenesis in brown adipose tissue (BAT) and “browning” of white AT (WAT) increase energy expenditure, thus promoting weight loss and protect against obesity. Recently, the microRNAs (miRNAs) that regulate...

Introduction: Bariatric surgery is an effective therapy for patients with type 2 diabetes mellitus (T2D). Many mechanisms have been proposed for its metabolic benefits, such as caloric restriction, weight loss, increased secretion of gut hormones like glucagon-like peptide 1 (GLP-1) and 2 (GLP-2), bile acid diversion, decrease of pancreatic and hepatic fat deposits and changes in gut microbiome.Aims: Evaluate changes after surgery in gut microbiome profi...

CRN04894 is a potent, orally bioavailable nonpeptide that is a highly selective antagonist for melanocortin type 2 receptor (MC2R). This receptor is found exclusively in the adrenal cortex and is the primary mediator of adrenal activation. We report results from a randomized, double-blinded, placebo-controlled (6 active:3 placebo/cohort), multiple ascending dose (40, 60, and 80 mg) study in health volunteers evaluating safety, pharmacokinetics, and pharmacodynamics of oral, on...

Introduction: Cardiac abnormalities are common in patients with acromegaly and contribute to the increased morbidity and mortality of the disease. Cardiac magnetic resonance (CMR) is the established, non-invasive gold standard for measuring morpho-functional changes of the heart. We aimed to detect cardiac alterations in patients with acromegaly through CMR and to identify potential risk factors associated with cardiac impairment.Materials and methods: T...

Purpose: Diagnosis of adrenal lesions requires hormonal investigation and morphological characterization; when CT and MRI imaging are equivocal, 18F-FDG-PET/CT could be a useful tool, although sensitivity and specificity varied among cohorts. The use of tumour-to-liver maximum standardized uptake values (SUVratio) was found to be accurate, but the best threshold value has not been identified yet. A SUVratio > 1.5 was associated with malignancy with a good performance. The ...

Introduction: Primary aldosteronism (PA) is the most frequent form of secondary hypertension. Over the past 10 years, important discoveries have been made regarding the genetic basis of aldosterone producing adenoma and familial forms of primary aldosteronism. In most cases, genetic abnormalities are found in genes coding for ion channels (KCNJ5, CACNA1D, CACNA1H, CLCN2) and pumps (ATP1A1, ATP2B3). These mutations affect intracellular ion homeostasis and/or c...

Introduction: Endogenous hypercortisolism is associated with cardio-metabolic complications and promotes the deposition of lipids in different tissues, particularly in the liver. However, the prevalence of hepatic steatosis in patients with Cushing’s syndrome (CS) has been little investigated so far and only one previous study reported a prevalence of 20% using computed tomography. The aim of the study is to evaluate the prevalence of hepatic steatosis and the organ-speci...

Rationale: Type 2 diabetes mellitus (DM) is common in patients with Cushing’s disease (CD) and Acromegaly (AC), and contributes to increased mortality. This study aimed at investigating the prevalence and characteristics of DM in CD and AC patients at diagnosis and after disease control (DC).Patients and Methods: 34 CD patients (8M,26F, 24 microadenomas(mA),6 macroadenomas (MMA) and 4 empty sella) and 35 AC patients (16M,19F, 7 mA,28 MMA) were inclu...

Purpose: IGF-1R antagonism reduces TED-related inflammation and proptosis. VRDN-001, a subnanomolar affinity full antagonist antibody to IGF-1R, is being evaluated in a phase 1/2 RCT (NCT05176639) at 3-20 mg/kg. We present results from the first cohort (10 mg/kg) of TED patients.Methods: Adults with active moderate-to-severe TED with clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo...