Endocrine Abstracts

Acromegaly is associated with increased soft tissue neoplasms, while GH deficient patients are protected from cancer development. Both environmental and age-related signals lead to cellular senescence and cell cycle dysregulation. We have shown that DNA damage-induced cellular senescence increases GH by inducing p53. GH, in turn, suppresses tumor suppressor proteins in both pituitary and nonpituitary cells.These observations led us to propose that intracellular epithelial GH i...

Hormone-secreting anterior pituitary cells exhibit slow turnover rates. Subsequent postnatal alterations in pituitary size are determined throughout the lifespan by both extrinsic and intrinsic factors. Pituitary tumors account for ~15% of intracranial tumors and arise from differentiated anterior pituitary cell types, and are invariably benign. They may hyper-secrete hormones, or may be clinically silent. Although hypothalamic influences are permissive for adenoma growth, sev...

Growth hormone (GH) secreted by the anterior pituitary gland regulates skeletal growth, metabolism and body composition. Although several of these actions are mediated by production of hepatic and local tissue IGF1, GH also acts independent of IGF1. GH is mainly produced from the pituitary as a systemic endocrine hormone, yet is also expressed in local tissues acting in an autocrine/paracrine/intracrine manner. Locally produced non-pituitary GH (npGH) signals the GHR to induce...

Background: The SAGIT® instrument, designed to assist clinicians in staging and managing acromegaly, is undergoing validation. A descriptive analysis of SAGIT Validation study baseline data revealed discrepancies between investigator-evaluated disease-control status, disease activity, hormonal control, and treatment decisions in acromegaly.Objective: To describe the baseline characteristics of patients in the SAGIT® valida...

Introduction: Although biochemical markers of acromegaly disease activity, including GH and IGF1, may fluctuate from day-to-day, biochemical treatment response in clinical trials is generally monitored using single-point analyses. Accordingly, longitudinal evaluations may assess patient status more accurately. In a phase 3 trial, oral octreotide capsules (OOC) demonstrated sustained composite endpoint GH and IGF1 response for ≤13 months in 151 patients with acromegaly pr...

The pituitary is highly sensitive to cell cycle disruptions. Although CDK gene mutations have not readily been identified in human pituitary tumors, overexpression of cyclins and dysregulation of CDK inhibitors are encountered in pituitary adenomas, indicating the importance of CDK activation for potential therapeutic targeting. However, it is difficult to predict which CDK inhibitor(s) may be effective against particular tumor types in vivo. Therefore, animal models fa...

As optimal postoperative management of patients with clinically nonfunctioning pituitary adenomas (NFPA) is a matter of debate, the role of dopamine agonist (DA) therapy in this clinical setting was evaluated.Methods: Retrospective analysis of prospectively collected data was conducted at two pituitary referral centrer with different standard practices for post-operative management of NFPA: DA therapy or conservative follow up. Dopamine receptor 2 (D2R) ...

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:...