Endocrine Abstracts

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: 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: Grade 3 pancreatic neuroendocrine tumor (G3-PanNET) and neuroendocrine carcinoma (PanNEC) are both defined by Ki67>20% and/or mitoses >20 per 2mm2. PanNET and PanNEC are thought to be molecularly distinct entities and progression from PanNET to PanNEC is considered rare. MEN1, ATRX, DAXX, and TSC1/2 mutations are common in PanNET, while TP53, RB1, KRAS, and SMAD4 mutations are typical of PanNEC. Immunostains for ATRX/DAXX/p53/Rb aid in the classification of...

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...

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...