Endocrine Abstracts

Objective: Age-associated double negative (DN) B memory cells lacking surface expression of CD27 and immunoglobulin D (IgD) are associated with proinflammatory characteristics and higher disease activity in autoimmune diseases. We first characterized B cells phenotypes in women with and without polycystic ovary syndrome (PCOS). We then took an in vivo approach, transferring purified IgG extracted from serum of hyperandrogenic women with PCOS to mice to establish wheth...

Introduction: The hyperandrogenic in utero environment in pregnant women with polycystic ovary syndrome (PCOS) can affect embryo development and impair offspring health at adult age. Moreover, long term hyperandrogenic exposure also leads to unfavored changes to the mothers’ reproductive physiology, leading to miscarriage, preterm delivery, and perinatal mortality. The underlying mechanism(s) of pregnancy complications associated with PCOS and the consequence of ...

Introduction: Mutations in the succinate dehydrogenase gene (SDH) predispose to the development of paraganglioma (PGL) which arise from parasympathetic and extra-adrenal sympathetic-associated chromaffin tissues. Identification of an index case results in family ‘cascade’ screening, often of asymptomatic individuals.Aims: To identify prevalence of PGL tumours and elevated plasma metanephrines at first scre...

Introduction: Mutations in the succinate dehydrogenase gene (SDH) predispose to the development of paraganglioma (PGL) which arise from parasympathetic and extra-adrenal sympathetic-associated chromaffin tissues. Identification of an index case results in family ‘cascade’ screening, often of asymptomatic individuals.Aims: To identify prevalence of PGL tumours and elevated plasma metanephrines at first scre...

Background: Primary adrenal insufficiency (PAI) can be associated with significant morbidity in children of all ages, the most common cause being Congenital Adrenal Hyperplasia (CAH). Several other rare inherited causes of PAI have been identified over the years which lack diagnostic phenotypic or biochemical signs, leaving genetic testing as the only approach to make a definitive diagnosis. Our cohort involves >440 patients who presented with features of PAI – hypogl...

Background: Bone metastasis from gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) was once considered rare, but prevalence has recently been reported as high as 12%. Although bone metastasis has been associated with poor prognosis, the most frequent cause of mortality in this population remains liver failure when liver metastases are present. Thus, it remains unclear whether patients with concurrent liver and bone metastasis who receive liver directed therapy (LDT) w...

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...

Background: Germline pathogenic or likely pathogenic (P/LP) variants occur in approximately 10% of NEN patients with recent data suggesting a higher frequency in pancreatic NENs or paraganglioma/pheochromocytoma (PPGL). However, identification of VUS can complicate interpretation of germline results, particularly when diverse populations are under study and the optimal gene panel size for testing remains unclear.Methods: A single-center retrospective cha...

Currently, no treatment options exist to improve semen quality for the majority of infertile men. Proper interaction between germ and Sertoli cells in the testis is critical for sperm production, and a recent study suggested that Denosumab, an inhibitor of RANKL signaling, may stimulate sperm production in some infertile men. Here, we show in animal and human studies how expression of the RANKL signaling system is critical for both Sertoli cell function and the testicular resp...

Adrenal insufficiency (AI) is life-threatening and can present alone or in combination with other co-morbidities. Here we describe families with a novel association of AI with porphyria caused by biallelic mutations in protoporphyrinogen oxidase (PPOX) or coproporphyrinogen oxidase (CPOX). The porphyrias are a group of disorders caused by defects in one of eight enzymes within the haem biosynthetic pathway, divided into acute porphyrias, resulting in mainly n...