Hepatic safety of ketoconazole in Cushing's syndrome: results of a Compassionate Use Programme in France.

Objective: Ketoconazole (KTZ) is one of few available treatments for Cushing's syndrome (CS). Although KTZ has been associated with severe hepatotoxicity, little information is available about hepatic safety in CS. The aim of this study was to document changes in liver function in patients with CS treated with KTZ.

Resetting the Abnormal Circadian Cortisol Rhythm in Adrenal Incidentaloma Patients With Mild Autonomous Cortisol Secretion.

Context: Adrenal incidentalomas (AIs) are found commonly on axial imaging. Around 30% exhibit autonomous cortisol secretion (ACS) associated with increased cardiovascular events and death.

Objective: We hypothesized that AI/ACS patients have an abnormal cortisol rhythm that could be reversed by use of carefully timed short-acting cortisol synthesis blockade, with improvement in cardiovascular disease markers.

Efficacy and safety of mitotane in the treatment of adrenocortical carcinoma: A retrospective study in 34 Belgian patients.

Objectives: Evaluation of patient characteristics and mitotane use in the treatment of adrenocortical carcinoma (ACC) over a 4-year period in Belgium.

Material And Methods: This was a multicentre retrospective review of the outcome of 34 patients treated with mitotane for ACC during the period [01/2008-12/2011] (12 diagnosed before and 22 diagnosed during the study period) and evaluated up to 06/2013.

Results: Patient and tumour characteristics were consistent with those generally described for ACC.

Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells.

Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane is the most effective medical therapy for adrenocortical carcinoma, but its molecular mechanism of action remains poorly understood. Although mitotane is known to have mitochondrial (mt) effects, a direct link to mt dysfunction has never been established. We examined the functional consequences of mitotane exposure on proliferation, steroidogenesis, and mt respiratory chain, biogenesis and morphology, in two human adrenocortical cell lines, the steroid-secreting H295R line and the non-secreting SW13 line.

Mifepristone reduces insulin resistance in patient volunteers with adrenal incidentalomas that secrete low levels of cortisol: a pilot study.

Background: Incidental adrenal masses are commonly detected during imaging for other pathologies. 10% of the elderly population has an 'adrenal incidentaloma', up to 20% of these show low-grade autonomous cortisol secretion and 60% of patients with autonomous cortisol secretion have insulin resistance. Cortisol excess is known to cause insulin resistance, an independent cardiovascular risk marker, however in patients with adrenal incidentalomas it is unknown whether their insulin resistance is secondary to the excess cortisol and therefore potentially reversible.

Plasma concentrations of o,p'DDD, o,p'DDA, and o,p'DDE as predictors of tumor response to mitotane in adrenocortical carcinoma: results of a retrospective ENS@T multicenter study.

Context: In patients with adrenocortical carcinoma (ACC) mitotane activity has been suggested to depend on plasma levels 14 mg/liter or greater and metabolite formation.

Objective: The study was performed to confirm the correlation of the currently used mitotane (o,p'DDD) threshold of 14 mg/liter with tumor response and to evaluate the additional value of 1,1-(o,p'-dichlorodiphenyl) acetic acid (o,p'DDA) and o,p'DDE (1,1-(o,p'-dichlorodiphenyl)-2,2 dichloroethene) levels for predicting tumor response.

Subjects/methods: Plasma samples collected within 3 months of best response from 91 patients on mitotane therapy for advanced ACC were analyzed retrospectively.

Effect of an educational program (PEGASE) on cardiovascular risk in hypercholesterolaemic patients.

Background: Many studies have demonstrated a gap between guidelines for the prevention of cardiovascular disease (CVD) and their implementation in clinical practice.

Aim: The PEGASE education program has been devised with an aim to improve the management of patients at high risk of CVD.

Methods: In a multicentre study carried out from 2001-2004 in France, 96 participating physicians were randomized into a "trained" group, which included 398 "educated" patients, and a "non-trained" group, which included 242 "non-educated" patients.

Patients' and physicians' perceptions and experience of hypercholesterolaemia: a qualitative study.

Background: A better understanding of patients' and physicians' perceptions and experience of hypercholesterolaemia will help to improve cardiovascular disease prevention and aid the development of appropriate educational strategies.

Aim: To identify perceptions, experience, educational needs, and barriers to learning in hypercholesterolaemic patients at high risk of cardiovascular disease.

Design Of Study: A qualitative study involving interviews with 27 hypercholesterolaemic outpatients and 21 physicians.

Lipoprotein lipase activity and common gene variants in severely hypertriglyceridemic patients with and without diabetes.

Objectives: In severe type IV hypertriglyceridemia (triglyceride levels >10 g/l), it is yet unknown whether lipoprotein lipase (LPL) differs according to the presence or not of diabetes.

Methods: We compared LPL activity and the presence of four common variants in the LPL gene (Asp 9 Asn (exon 2), Gly 188 Glu (exon 5), Asn 291 Ser (exon 6) and Ser 447 Ter (exon 9)) in a group of 34 patients of whom 17 presented diabetes mellitus.

Results: Maximum triglyceride, cholesterol levels and distribution of apolipoprotein E phenotypes did not differ between the two subgroups.