Endocrine Abstracts

Background: The well-differentiated grade 3 neuroendocrine tumor (G3NET) category was introduced in the 2017 WHO classification as a new category of high-grade neuroendocrine neoplasm (NEN). G3NET is thought to have worse overall survival (OS) than lower grade NET, but better OS than poorly differentiated neuroendocrine carcinoma (NEC). However, challenges in pathologic diagnosis and changes in terminology have limited our understanding of the G3NET category. We compared outco...

Background: Patients with neuroendocrine neoplasms (NENs) have chronic symptoms from hormone overproduction, tumor growth and metastasis, and side effects from prolonged treatment. We assessed the feasibility of using a digital health platform to recruit patients with NENs to evaluate symptoms and quality of life.Methods: eNET is a prospective, web-based, cohort study for patients with advanced NENs of any primary site, histologic grade, differentiation,...

Background: Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous, with grade (G) defined by Ki67 proliferation index (<3% G1, 3-20% G2, >20% G3) or mitotic rate. The G3 NEN subgroup is further divided into well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NEC). Grade progression can occur over time, with low-to-high grade progression (L-to-H; G1/2 to G3) the most clinically relevant form. It is associated w...

Background: Patients with neuroendocrine neoplasms (NENs) have a high burden of chronic symptoms. We assessed symptom burden and overall quality of life (QOL) for eNET study participants and analyzed differences by age, sex, and NEN primary site.Methods: eNET is a prospective, cohort study on the Eureka digital health platform enrolling individuals with advanced NENs. Participants completed validated surveys on an internet-supported device at baseline an...

Background: Data examining HLA associations in Addison’s disease (AD) from South Africa (SA) are limited. We wished to determine the HLA in South African AD patients either positive or negative for 21 hydroxylase autoantibodies (21 OH-AA) and matched healthy controls, hypothesising that certain HLA alleles could predominate, but there may be differences from Western countries.Methods: SA patients (n=73) were enrolled as part of a nationwide...

Bile acids (BAs) are synthesized by converting cholesterol in hepatocytes and recycling it via enterohepatic circulation. Most BAs are reabsorbed into hepatocytes, where they inhibit their own synthesis by activating FXR pathway. NTCP is a major transporter of BAs via absorption from portal blood into hepatocytes. Hepalatide is a 47aa synthetic peptide that specifically binds NTCP resulting in BA spillover of hepatocytes into the systemic circulation. In this way, BA synthesis...

Bile acids (BAs) are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). Modulation of bile acid profiles might affect the treatment of metabolic diseases, indicating new possible therapeutic avenues. The sodium taurocholate co-transporting polypeptide (NTCP) plays a pivotal role in the enterohepatic circulation of bile salts as the main uptake transpo...

Background: Gastrointestinal neuroendocrine tumors (GI NETs) are subdivided into grades (G) G1-G3 based on Ki-67 proliferation index (%) (G1<3%, G2 3-20%, and G3 >20%) or mitotic rate, with tumor grade informing prognosis and treatment. Grade progression (GP) over time in GI and pancreatic NETs has recently been identified, with low(G1/2)-to-high(G3) grade progression (L-to-H) the most clinically relevant form. L-to-H is associated with worse survival, yet the timefram...

Background: Pancreatic neuroendocrine tumors (panNETs) are heterogeneous, with grade (G) defined by Ki67 proliferation index (<3% G1, 3-20% G2, and >20% G3) or mitotic rate. Previous studies suggest that baseline Ki67 index may be confounded by biopsy site (primary or metastasis), biopsy technique and primary tumor size. Ki67 differences leading to grade discordance in PanNETs at baseline is relatively understudied. Our study aims to evaluate grade discordance in synch...

Background: The incidence of germline pathogenic/likely pathogenic variants (P/LPV) is relatively well described in low grade well differentiated neuroendocrine tumors (NETs). However, germline findings in G3 NENs including grade 3 NETs (G3NET) and poorly differentiated neuroendocrine carcinoma (NEC) is gravely understudied, and guidance related to germline testing in G3NEN is lacking.Methods: An IRB approved, single institution, retrospective chart revi...