Endocrine Abstracts

Introduction: Rapid and sustained decreases in UFC and significant improvements in signs and symptoms were seen in a large, randomized, 12-month phase III study of pasireotide in Cushing’s disease. The safety profile of pasireotide was found to be similar to that of other somatostatin analogues, with the exception of hyperglycemia-related AEs (reported in 72.8% of patients). This abstract reports safety data from a 12-month extension to this phase III trial.<p class="...

Introduction: Alternative to transsphenoidal pituitary surgery (TSS) may be required in Cushing’s disease (CD), as first or second line treatment. 1,ortho-1,para′-dichloro-diphenyl-dichloroethane (o,p′DDD) has a potent anticortisolic action. Its place in CD treatment is not well defined. The aim of this study was to further evaluate the efficacy and tolerance of o,p′DDD in CD.Patients and m...

The outcome of ACTs can be determined by gene expression level at the RNA level. However RNA handling is challenging. In contrast tumor DNA is robust and therefore easier to use.Aim: To characterize the ACTs DNA alterations; to identify markers with diagnostic and prognostic value using tumor DNA.Methods: The mapping of chromosomal gains and losses of 60 ACTs (39 adenomas (ACAs), 21 carcinomas (ACCs)) was performed with CGH arrays ...

Tissue samples from adrenal tumors provide the basis for standard diagnostic procedures such as pathological examination. In addition, these tumor samples have been an invaluable source for the discovery of novel molecular pathways involved in adrenal tumorigenesis. Information on the molecular phenotype are based on DNA mutation analysis and epigenetic changes, RNA and protein expression pattern and sub-cellular localization as well as post transcriptional protein modificatio...

Background: ARMC5 (armadillo repeat containing 5) has been identified as the gene responsible for PBMAH (Primary Bilateral Macronodular Adrenal Hyperplasia). ARMC5 inactivating mutations are reported in 20 to 25% of PBMAH patients. ARMC5, is considered as a tumor suppressor gene controlling apoptosis and regulating steroidogenesis. The mechanisms of action of ARMC5 are unknown. The structure of the ARMC5 protein contains ARM repeats and a BT...

Introduction: ARMC5 germline and somatic inactivating mutations were discovered in patients treated by adrenalectomy for hypercortisolism due to primary bilateral macronodular adrenal hyperplasia (PBMAH). Since then, several ARMC5 germline variants have been described in PBMAH patients. Genetic alterations are spread all over ARMC5 coding sequence and many are missense variants. For them, geneticist conclusions are based on in silico predictions. As ...

IntroductionThe oral 11β-hydroxylase inhibitor, osilodrostat, normalized mean urinary free cortisol (mUFC) in 79% (15/19) of patients with Cushing’s disease at the end of the 22-week core LINC 2 study. Long-term efficacy and safety data following an optional extension phase are reported here.MethodsPatients with clinical benefit at week 22 could continue receiving osilodrostat during the extension; ...

Introduction: Osilodrostat is a new 11 ß-hydroxylase inhibitor with a mode of action analogue to metyrapone. It has become increasingly used in recent years for treatment of Cushing’s Syndrome (CS). However, few in vivo studies are currently available to accurately compare both drugs characteristics. The objective of our study was to compare steroidogenic profiles in patients treated by either Osilodrostat or Metyrapone for ACTH-dependent CS.Me...

Background: Cushing’s syndrome, caused by an excess of circulating glucocorticoids, is associated with high morbidity and presents high inter-individual variability. The earlier the diagnosis, the better the treatment effectiveness and the prognosis. Hormone assays, routinely used, contribute to identify Cushing’s syndrome. However, no biomarker is currently available to directly quantify the biological action of glucocorticoids. Blood samples represent an easily obt...

Introduction: Biological diagnosis of Cushing syndrome relies on three parameters: 24 hours-free urinary cortisol; serum cortisol after 1 mg dexamethasone suppression test; late-night serum or salivary cortisol. These tests allow the diagnosis of cortisol excess but do not help in etiological diagnosis, particularly in the distinction between pseudo-Cushing and ACTH-dependent Cushing syndrome, which is often challenging. The aim of this study was to evaluate the performances o...