Endocrine Abstracts

Glucocorticoid (GC) excess drives obesity, insulin resistance and type 2 diabetes. Obstructive sleep apnoea (OSA) is a prevalent condition associated with both activation of the hypothalamic-pituitary-adrenal (HPA) axis and an adverse metabolic phenotype. However, a causal link between these two features has not been established. We designed a novel human model of intermittent hypoxia (IH) aimed at replicating the systemic insulin resistance associ...

Glucocorticoid (GC) excess drives obesity, insulin resistance and type 2 diabetes. Obstructive sleep apnoea (OSA) is a prevalent condition associated with both activation of the hypothalamic-pituitary-adrenal (HPA) axis and an adverse metabolic phenotype. However, a causal link between these two features has not been established. We designed a novel human model of intermittent hypoxia (IH) aimed at replicating the systemic insulin resistance associ...

A 37 year old lady with relapsing Graves’ thyrotoxicosis initially managed on a ‘block and replace regime’ with propylthiouracil and levothyroxine for 7 years had her medication changed to carbimazole after a relapse from non-compliance but developed agranulocytosis. She was then restarted on an increased dose of propylthiouracil alone. Two weeks later, she developed tender purpuric lesions and was admitted after developing painful bullous lesions to her lower l...

Hyperthyroidism has been linked to long-term cardiovascular and metabolic morbidity and increased mortality. We aimed to assess differences in mortality and cardiometabolic outcomes depending on treatment modality to better inform patient-clinician decision-making.Methods: We identified 62,474 patients with newly diagnosed hyperthyroidism, treated with antithyroid drugs (ATD), radioiodine or thyroidectomy from a UK population-based GP database (>16M ...

Background: Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) are a rare subset of cancers which nevertheless are a rising health burden. Development of new therapies suffers from several bottlenecks, including low patient accrual and poor understanding of tumor characteristics. Patient tumor organoids (PTOs) are a novel model capable of improving screening of patient tissue in an accurate, standardized, and high-throughput capacity. In this study, we utilized patient...

Background: Neuroendocrine tumors (NETs) are a heterogeneous group of malignant neoplasms arising from neuroendocrine cells distributed throughout the body. The most common sites of NETs are the gastrointestinal tract, pancreas and lungs. The clinical management of NETs is not standardized, with few FDA-approved therapies. Moreover, drug development has been challenging for NETs due to limited pre-clinical models. To address this unmet need, the NCI Natural History Study of Ch...

Post-translational modifications of histones such as methylation, acetylation, and phoshorylation regulate chromatin structure and gene expression. However, phosphorylation of histone H3 at threonine 11 (H3T11ph) has not been linked to transcriptional regulation. Here we show that protein kinase C-related kinase 1 (PRK1) phosphorylates H3T11 upon ligand-dependent recruitment to androgen receptor (AR) target genes. PRK1 is pivotal to AR function since PRK1 knockdown by RNAi or ...

Background: Octreotide LAR is a long-acting somatostatin analogue used in the management of metastatic neuroendocrine tumors (NETs), with antiproliferative and symptom control effects. It requires intramuscular (IM) injection. Missed IM injections can cause subcutaneous nodules (SCNs) on radiologic images. We reviewed the rates of SCNs in a real-world cohort of NETs receiving octreotide LAR and explored treatment outcomes.Methods: Patients with gastroint...

Background: Accurate imaging is essential for NETs. 111In-octreotide scintigraphy, 68Ga-DOTATOC PET/CT and 18F-FDG PET/CT are the most commonly used modalities. This study compared the three modalities to ascertain the added value of newer functional imaging approaches.Methods: A retrospective review was performed on patients who underwent 68Ga-DOTATOC PET/CT and 18F-FDG PET/CT between 07/2018 and 03/2023 as part of a clinical trial at BC Cancer. Patient...