Endocrine Abstracts

Adrenal tumors – like many endocrine tumors – bear two classical threats: hormone hypersecretion and/or oncogenic potential. Also, because they are rare, their recognition may be delayed; and syndromic- or malignant tumors may be misdiagnosed…adding further threats…This talk will concentrate on recent progress brought by genetic studies with the aim of improving our understanding of the pathophysiology of these tumors, our diagnosti...

Xavier Bertagna, Cochin Hospital, Paris, France. AbstractXavier Bertagna is Professor of Endocrinology, Chief of the Department of Endocrinology of Cochin hospital, Faculté de Médecine René Descartes, Université Paris, Paris, France.He trained at the Clinical Research Center (Dr. M. Chrétien), Montreal, Canada and at the Endocrine Division, Vanderbilt Medical School (Dr....

Many difficulties can be encountered in the management of patients with Cushing’s syndrome or suspected Cushing’s syndrome.In the first step of the diagnosis strategy, establishing the state of chronic hypercortisolism may be hampered by a number of pitfalls: drug interaction (inducers of high CBG levels, liver enzyme inducers, glucocorticoids, antiglucocorticoid RU 486, Glycyrrhetinic acid); intercurrent pathologic states (obesity, thyroid dys...

Drug interactions, intercurrent pathological states may interfere with routine diagnostic tests. Authentic hypercortisolic states can be present without Cushing’s syndrome, such as in depression, anorexia nervosa, alcoholism, pregnancy. Mild forms of Cushing’s syndrome, or fluctuating cases are other usual pitfalls.When the diagnosis of Cushing’s syndrome is firmly established there are still many potential pitfalls in the etiological diag...

Some elegant clinical observations of dysregulated cortisol-secretion in cases of ACTH-independent macronodular hyperplasia (AIMAH) and more rarely adrenocortical adenomas (ACA) have led to the concept of ‘aberrant’ or ‘illegitimate’ membrane receptors (AR) in adrenal Cushing syndrome. It this situation cortisol secretion is regulated by an extra-cellular ligand that usually does not stimulate cortisol secretion in normal adrenals. This abnormal response mi...

Illicit expression of membrane receptors for circulating regulatory factors, such as GIP and LH receptors, has been well documented in ACTH-independent macronodular adrenal hyperplasias (AIMAHs) causing Cushing’s syndrome. In addition, we have observed an abnormal expression of serotonin, arginine vasopressin and ACTH in a subpopulation of steroidogenic cells in two AIMAH tissues. The aim of the present study was: (i) to investigate the presence of ACTH by immunohistochem...

Introduction: MSC is a simple and reliable mean to diagnose hypercortisolism, yet its value to asses the outcome of treatment has rarely been addressed.Objective: Compare MSC and other classical parameters, to assess the outcome of TSS in CD.Patients and methods: Sixty-eight patients from a single Center operated for CD between 1996 and 2006. Outcome was assessed between 6–12 months post TSS. Remission was defined as: morning ...

Background: In the 22-week LINC-2 study, osilodrostat (LCI699), a potent oral 11β-hydroxylase inhibitor, normalized urinary free cortisol (UFC) levels in 15 of 19 patients with Cushing’s disease (CD). The most common AEs were nausea, diarrhea, asthenia, and adrenal insufficiency (n=6 each). Here, we report the 31-month efficacy and safety results from LINC-2 extension.Methods: Patients receiving clinical benefit at week 22 could enter ...

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 ...

Background: A proof-of-concept study (LINC 1) demonstrated that after 10 weeks, LCI699 normalized UFC in 11/12 patients with Cushing’s disease. This interim analysis of the first eight patients enrolled into a longer-term study (LINC 2) further evaluates LCI699 in Cushing’s disease; the full analysis on all 19 enrolled patients is expected in time for the congress.Methods: There were two study groups. Previous LINC 1 participants (follow-up coh...