Endocrine Abstracts

Mark E Molitch, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA AbstractMark E. Molitch, MD, is Professor of Medicine and a Member of the Division of Endocrinology, Metabolism and Molecular Medicine at Northwestern University Feinberg School of Medicine, in Chicago, Illinois. Prior to joining the faculty at Northwestern in 1984, Dr. Molitch was an Associate Professor at Tufts University School of...

Prolactinomas usually present because of reproductive/sexual dysfunction due to the hyperprolactinemia but they may also present because of mass effects. Prolactin (PRL)-secreting microadenomas enlarge in only about 7% of cases, so many can be followed without direct treatment, although sex steroid hormone replacement may be required. Dopamine agonists can normalize PRL levels in over 90% of cases and can reduce tumor size significantly in over 75%, with cabergoline being gene...

Post-translational modifications of histones such as methylation, acetylation, and phoshorylation regulate chromatin structure and gene expression. However, phosphorylation of histone H3 at threonine 11 (H3T11ph) has not been linked to transcriptional regulation. Here we show that protein kinase C-related kinase 1 (PRK1) phosphorylates H3T11 upon ligand-dependent recruitment to androgen receptor (AR) target genes. PRK1 is pivotal to AR function since PRK1 knockdown by RNAi or ...

Introduction: Chronic hypercortisolemia during Cushing Syndrome (CS) determines significant changes in the plasticity and function of metabolic tissues like visceral adipose tissue (VAT). Persistence of alterations in VAT function after CS remission is under debate, as data of clinical studies is not consistent due to confounder factors and limited availability of VAT. Animal model of reversible CS presents long-term alterations on VAT after remission. We investigate VAT alter...

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 ...

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...

Background: Many patients with acromegaly report limitations of long-acting somatostatin receptor ligand (SRL) injections, including ongoing disease symptoms near cycle-end and injection-site pain. Oral octreotide capsules (OOC) may provide an alternative to monthly injections. The phase 3 CHIASMA OPTIMAL study assessed efficacy and safety of OOC in patients with acromegaly controlled on injectable SRLs.Methods: A multinational, randomized, placebo-contr...

Background: Injectable somatostatin receptor ligands (SRLs) are currently the most widely used therapy for acromegaly. Oral octreotide capsules (OOC) are a potential therapy for acromegaly; the safety and efficacy were evaluated in the CHIASMA OPTIMAL pivotal study (Samson et al. ENDO 2020). As reported, mean IGF-I levels of the OOC group were maintained within normal range at end of treatment in all patients. However, some patients may not respond to OOC treatment (2...

Background: Oral octreotide capsules (OOC) are a treatment option for patients with acromegaly in the United States. The MPOWERED trial (NCT02685709) showed that OOC were noninferior to injectable somatostatin receptor ligands (iSRLs; octreotide or lanreotide) in maintenance of biochemical control in patients previously responding to both treatments, as well as demonstrated improvements in patient-reported outcomes among patients receiving OOC.Objective:...

Background: Oral octreotide capsules (OOC) are a treatment option for patients with acromegaly in the United States who have previously responded to injectable somatostatin receptor ligands (iSRLs, octreotide or lanreotide). In previous phase 3 studies, the safety of OOC was shown to be consistent with iSRLs, without dose-dependent adverse reactions. In the double-blind, placebo-controlled period (DPC) of the CHIASMA OPTIMAL trial (NCT03252353), patients were randomized to twi...