Endocrine Abstracts

Introduction: PATRO adults is an ongoing, international, open, longitudinal, non-interventional study of the long-term safety and efficacy of Omnitrope (Sandoz), a recombinant human GH (rhGH). This study will provide additional data on the long-term safety of rhGH in adult patients with severe GH deficiency (GHD). Here, we present safety data from an interim analysis.Methods: Eligible patients are male or female adults who are receiving treatment with Om...

Glucocorticoid feed-back in pituitary corticotrophs represses POMC transcription and ACTH release. Serum and glucocorticoid-induced kinase 1 (Sgk1) has been identified as an immediate early target of glucocorticoids in many tissues, however its expression and function in corticotrophs are unknown.We show here that Sgk1 is present in the human pituitary gland at both mRNA and protein levels. Double-immunohistochemistry revealed that Sgk1 is expressed in d...

Background: In acromegaly, few in vivo data exist on changes of the brain parenchyma as a pathology caused by systemically elevated levels of GH and IGF-1. This is in contrast to neuropsychiatric symptoms such as depression, cognitive impairment, personality changes and pain syndromes that accompany the condition. We aimed at measuring brain tissue volumes and white matter pathology in acromegaly.Methods: Forty-three patients (age 54±14 years...

Folliculostellate (FS) cells were found to regulate hormonal secretion in pituitary endocrine cells. This cell type share properties with components of the innate immune response such as dendritic cells and macrophages, and it is suggested that they are able to initiate immune responses and act as part of an immunoendocrine regulation system. Members of toll-like receptor (TLR) family recognize bacterial cell wall components and initiate an immune response. Recently, we detect...

The tumorigenesis of Cushing’s disease is characterized by somatic mutations in the USP8 gene in almost half of the cases. USP8 encodes for ubiquitin specific protease 8, a deubiquitinase that rescues proteins involved in the regulation of ACTH synthesis in corticotroph cells. In the present study we tested the antisecretory and antiproliferative efficacy of a commercially available specific USP8 inhibitor (IC50 3.1 μM USP8; >90 μM USP7) in immortalized muri...

Background: Endogenous Cushing’s syndrome (CS) is rare with an estimated yearly incidence of 1–3 patients/million. CS describes a group of diseases that have in common an excess secretion of glucocorticoids which results in a characteristic clinical phenotype. Severe courses of Cushing’s syndrome are characterized by a break-down of protein catabolism translating into clinical consequences including muscle weakness. While remission of CS is achievable by surgica...

Background: Cushing’s syndrome (CS) is a chronic disorder characterized by endogenous cortisol excess resulting in long-term metabolic and cardiovascular consequences. The identification of metabolic alterations related to hypercortisolism could be beneficial in tailoring treatments of co-morbidities. Our aim was to characterize the metabolic alterations of patients with hypercortisolism by targeted plasma metabolomic profiling.Methods: Subjects (<e...

The factors triggering pancreatic neuroendocrine tumor (PanNET) progression are largely unknown. Here we investigated the role and mechanisms of the sumoylation enhancing protein RSUME in PanNET tumorigenesis. Immunohistochemical studies showed that RSUME is strongly expressed in normal human pancreas, in particular in β-cells. RSUME expression is reduced in insulinomas and is nearly absent in other types of PanNETs suggesting a role in PanNET tumorigenesis. In human panc...

Introduction: Cushing’s syndrome (CS) is a rare disease characterized by clinical features that show overlap with the ‘metabolic syndrome’. Pilot studies regarding the use facial image analysis software as a novel diagnostic tool in acromegaly and CS have shown promising results. Distinguishing CS patients from patients that show similar features without true hypercortisolism remains a challenge in clinical practice. To address this particular problem, we evalua...

Introduction: Sex steroid hormones exert a wide range of effects on metabolism. New techniques such as metabolomic profiling allow for a deeper insight into metabolic regulation. In epidemiological samples it has been demonstrated that most of these metabolites show sex-specific differences. However, if these differences are attributable to the effects of sex hormones or genetics is little understood so far.Methods: We performed targeted metabolomics pro...