Endocrine Abstracts

Introduction: The present study is designed to evaluate the efficacy and safety of pasireotide-long-acting release (LAR) in patients with acromegaly inadequately controlled after ≧3 mo treatment with the maximal approved doses of first-generation SSAs.Methods: Phase IIIb, multicentre, single-arm, open-label study.Patients: Adults (N~112) with inadequately controlled acromegaly (mean GH>1 μg/l and IGF-1>1.3xULN) desp...

Introduction: In PAOLA study, pasireotide showed superior efficacy over continued treatment with octreotide/lanreotide in patients with inadequately-controlled acromegaly; 64% of patients receiving pasireotide long-acting release (LAR) reported hyperglycaemia-related adverse events. Pasireotide has been shown to inhibit insulin secretion. The aim of this exploratory analysis was to investigate the effect of timing of antidiabetic medication (ADM) intervention on the fasting pl...

Introduction: High affinity binding of pasireotide for both sst2 and sst5 leads to its enhanced efficacy in treatment of acromegaly but results in decreased secretion of insulin, incretins (GLP-1 and GIP) and, to a lesser extent, glucagon. Metformin may be a good option in patients with acromegaly experiencing hyperglycaemia with pasireotide as it improves GLP-1 secretion. We analysed data from a 12-month, Phase III, randomised study in medically naï...

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...

Objective and methods: Recent studies suggest that altered alternative splicing and, consequently, appearance of an abnormal splicing pattern and even of aberrant/oncogenic splicing-variants, represent a common molecular feature of most tumor pathologies, including Pituitary Neuroendocrine Tumors (PitNETs). However, the putative alteration, pathophysiological role and potential therapeutic utility of splicing machinery components [i.e. spliceosome-components (SCs) and splicing...

Introduction: Heterozygous mutations in the AIP gene are associated with young-onset pituitary adenomas while homozygous loss of AIP in animal models is lethal. As early diagnosis could lead to better outcomes, family members of AIP mutation-positive patients need follow up. The R304Q variant is commonly described as pathogenic based on clinical assessment. However, it is also present in the general population (minor-allele-frequency (MAF) 0.0007&#15...

Introduction: The PAOLA study in patients with inadequately-controlled acromegaly (n=198) demonstrated superior efficacy of pasireotide long-acting release (LAR; 40 mg/60 mg) in biochemical control (GH <2.5 μg/l and normalized IGF-1) vs continued treatment with octreotide LAR 30 mg/lanreotide Autogel 120 mg (15.4% and 20.0% vs 0%). Here we report preliminary data from the extension phase of PAOLA at wk28.Methods: Pasireotide-LAR (40 mg/...

The intrinsic heterogeneity of endocrine-related cancers (ERCs) hampers the identification and development of global and effective therapeutic treatments for these pathologies. However, the dysregulation of the splicing process has been postulated as a new common hallmark shared by most cancer types, since it is associated with the appearance of splicing variants with oncogenic potential (e.g. CD44v6, BCL-Xs, AR-v7, SST5TMD4, In1-ghrelin...

Recent studies have reported a high prevalence of USP8 mutations in corticotroph adenomas causing Cushing’s disease. Nelson’s syndrome is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory Cushing’s disease that is caused by the development of an ACTH-secreting tumor in the pituitary gland. Whether USP8 alterations are also present in Nelson’s tumors has not been studied in detail so far....

We have recently reported that somatic mutations in the ubiquitin-specific protease 8 (USP8) are present in corticotropinomas of patients with Cushing’s disease and that these mutations reduced the interaction with 14-3-3. Mutant USP8 exhibited higher deubiquitination activity and potentiated EGFR-induced POMC expression (Reincke et al., Nat Genet 2014). To further study the prevalence of these mutations, we have analyzed 134 ACTH-producing corticotropin...