Endocrine Abstracts

Elevated insulin levels are correlated with colonic adenomas and carcinomas in the general population. Patients with acromegaly are considered at high risk to develop colonic lesions and have a high insulin levels. To evaluate the role of insulin levels on colonic polyps (hyperplastic, adenomatous, single or synchronous) or adenocarcinoma in acromegaly we designed this analytical, observational, open, prospective, study enrolling 189 patients (100 women, 89 men, age 20–82...

The most frequent cause of death in acromegaly is cardiomyopathy. To evaluate determinants of the acromegalic cardiomyopathy we performed an analytical, observational, open, prospective, controlled study in 205 patients with active acromegaly (108 women and 97 men) and 205 non-acromegalic subjects sex- and age-matched with the patients. We determined the prevalence of Left Ventricular (LV) hypertrophy (LVH), diastolic and systolic dysfunction, by echocardiography- measured LV ...

Background: Improving physical manifestations of hypercortisolism is an important treatment goal for patients with Cushing’s disease (CD). In the Phase III LINC 3 study (NCT02180217), osilodrostat therapy, a potent oral 11β-hydroxylase inhibitor, rapidly normalised mean urinary free cortisol (mUFC) in most patients with CD and sustained control of mUFC over a median treatment period of 130 weeks (W). Here we describe concomitant improvements in physical manifestation...

Introduction: Osilodrostat decreases cortisol production by inhibiting 11β-hydroxylase, increasing adrenal hormones above the blockade. Here, we describe these effects of osilodrostat and associated adverse events (AEs). The efficacy and safety of osilodrostat in patients with Cushing’s disease (CD) were confirmed in the published Phase III, prospective LINC 3 study (NCT02180217).Methods: 137 patients with CD (mUFC >1.5x upper limit of norm...

Background: 24-h mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC) levels are complementary parameters recommended for screening and monitoring treatment response in patients with Cushing’s disease (CD). In the published core period of the Phase III LINC 3 study (NCT02180217), therapy with osilodrostat (potent oral 11β-hydroxylase inhibitor) produced rapid, sustained reductions in mUFC and LNSC alongside improvements in clinical signs of hyper...

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 ...

Introduction: A monthly, long-acting formulation of pasireotide normalized or reduced mean urinary free cortisol (mUFC) in most patients with Cushing’s disease (CD) in a multicentre, double-blind, Phase III study. The effects of long-acting pasireotide on signs and symptoms of CD are reported here.Methods: Patients with persistent/recurrent (n=123) or de novo (non-surgical candidates; n=27) CD and mUFC≥1.5–5xULN...

Introduction: Generously supported by IPSEN)-->Measurement of salivary cortisol is a simple, convenient, accurate and reproducible technique with potential value during the diagnosis/management of hypercortisolism. Current analysis evaluates changes in late-night salivary cortisol (LNSC) during pasireotide treatment in patients with Cushing’s disease (CD).Methods: A 12 m, Phase III study enrolled 162 adult...

Somatostatin (SSTRs) and dopamine (DRs) receptors are expressed in adrenal tumors. It has been demonstrated in pituitary and neuroendocrine tumors that somatostatin-dopamine chimeric molecules, namely dopastatins, which bind both somatostatin (SST2 and/or SST5) and dopamine (D2) receptors, exert a more potent action compared with the single receptor agonists in experimental settings. The aims of this study were to evaluate the expression of DRs and SSTRs, and the effects of do...

The dopamine agonist cabergoline has been found to be effective in inducing normalization of cortisol secretion in 25–50% of patients with Cushing’s disease after long-term treatment. Moreover, tumor shrinkage have been documented in selected patients with pituitary corticotroph tumors. The aim of the present study was to evaluate the effect of cabergoline withdrawal in patients with a stable normalization of cortisol secretion and stable or absent visualization of p...