Endocrine Abstracts

Autonomy of ACTH secretion has been described in patients with chronic dysinhibition of ACTH secretion. We here present the very unusual case of a 31-year old female patient who had congenital adrenal hyperplasia and developed Cushing’s disease, including clinical examinations, laboratory data, endocrine function tests, histological and genetic analyses.The affected patient had clinical signs and a typical history of hypercortisolism. Endocrine func...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The role of glucocorticoids (GC) in its pathogenesis, is highlighted in patients with GC excess, Cushing’s syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although circulating cortisol levels are normal in patients with NAFLD, hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11&#94...

Paltusotine is a once-daily, oral selective nonpeptide somatostatin receptor type 2 (SST2) agonist, which is in clinical development for the treatment of acromegaly. Maintenance of insulin-like growth factor 1 (IGF-1) control and toleration was demonstrated in phase 2 studies evaluating paltusotine in biochemically controlled (IGF-1 ≤1xULN) [ACROBAT Evolve (NCT03792555)] and uncontrolled (1> IGF-1 ≤2.5xULN) [ACROBAT Edge (NCT03789656)] patients with acromegaly ...

Paltusotine is a once-daily, oral, nonpeptide somatostatin receptor type 2 (SST2) specific agonist, in development for the treatment of acromegaly and neuroendocrine tumors. We report interim results from ACROBAT Advance (NCT04261712), an ongoing, multicenter, open-label, long-term extension study of paltusotine in subjects with acromegaly who previously completed either Phase 2 study ACROBAT Edge (NCT03789656) or Evolve (NCT03792555). ACROBAT Edge enrolled 47 subjects with el...

Background: Hot flushes (HF) affect 70% of menopausal women and can be debilitating. Oestrogen administration is effective but not without risk. Neurokinin B signalling is increased in menopausal women, and is likely critical in the aetiology of their HF. We therefore hypothesised that a neurokinin 3 receptor (NK3R) antagonist could attenuate menopausal flushing.Design: This single-centre, phase 2, randomised, double-blind, placebo-controlled, crossover ...

Background: Hot flushes (HF) affect 70% of menopausal women and can be debilitating. Oestrogen administration is effective but not without risk. Neurokinin B signalling is increased in menopausal women, and is likely critical in the aetiology of their HF. We therefore hypothesised that a neurokinin 3 receptor (NK3R) antagonist could attenuate menopausal flushing.Design: This single-centre, phase 2, randomised, double-blind, placebo-controlled, crossover ...

Prostate cancer (PCa) is the most frequent cancer in men in the western world. PCa growth is highly dependent on androgens and androgen ablation is the cornerstone of current therapeutic approaches. μ-Crystalline (CRYM) is the main component of the kangaroohs eye’s lens. CRYM binds thyroid hormone (T3) in a NADPH dependent manner thereby sequestering it from being transcriptionally active in the nucleus. The role of CRYM in prostate cancer is largely unknown. This st...

Background: Metastatic neuroendocrine neoplasms (NENs) constitute a heterogeneous group of uncurable cancers with limited treatment options. Lenvatinib is an oral multiple kinase inhibitor that showed activity in gastroenteropancreatic neuroendocrine tumors in the phase II Talent Trial at a starting dose of 24 mg per day. Although a confirmatory phase III study was never conducted, the drug is available for use off-label.Methods: We retrospectively revie...

Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. Through ChIP-seq analyses, we presviously identified direct target genes of ERα acting in complex with SRC1, SRC2 or SRC3 (Zwart et al., 2011 EMBO J). Only the 111 genes there were under direct control of ERα in conjunction with SRC3 (but not the other two p160s) predicted...

Background: PWS is a rare neurodevelopmental genetic disorder characterized by hyperphagia, obesity, hormonal deficiencies, and problem behaviors for which there are no approved treatment. DCCR administration (100-525 mg/day) up to 52 weeks in participants with PWS improved hyperphagia, behavior, body composition and metabolic markers.Objective: The objective of this study was to compare changes in hyperphagia (using Hyperphagia Questionnaire for Clinica...