Endocrine Abstracts

The aim of this study was to evaluate in a long follow-up time patients with acromegaly successfully treated by transphenoidal surgery (TNS) in order to establish the recurrence rate and the need of subsequent follow up.Methods: We retrospectively analyzed data of 283 acromegalic patients (168 females, mean age: 44.2 ±12.9 years) who underwent TNS for a GH secreting pituitary adenoma between 1980 and 2020, on regular follow-up at two Pituitary Units...

Background: Skeletal fragility is an important clinical issue in women with early-stage breast cancer and men with non-metastatic prostate cancer under hormonal hormone deprivation therapies (HDTs). Vertebral fractures (VFs) have been reported in a remarkable number of subjects exposed to HDT especially when the diagnosis of fractures is performed by a radiological and morphometric approach. Notably, prediction of fractures in this clinical setting is a challenge and determina...

Somatic mutations in the ubiquitin specific peptidase 8 (USP8) gene have been associated with higher levels of somatostatin (SS) receptor subtype 5 (SSTR5) in adrenocorticotroph hormone (ACTH)-secreting pituitary neuroendocrine tumors (PitNETs). However, a correlation between the USP8 mutational status and favorable responses to pasireotide, the somatostatin multi-receptor ligand acting especially on SSTR5, has not been investigated yet. Here, we studied the impact of USP8 mut...

The mTOR inhibitor everolimus has been shown to display antimitotic effects on diverse neoplasms, including pituitary neuroendocrine tumors (PitNETs); however, its effect is reduced by an escape mechanism that increases AKT phosphorylation (P-AKT) leading to survival pathway activation. Dopamine receptor type 2 (DRD2) reduces p-AKT in some non-functioning PitNETs (NF-PitNETs) and in lactotrophs MMQ cells, through a α-arrestin 2-dependent mechanism. This study aim...

The main target of pharmacological therapy for growth hormone (GH)-secreting pituitary tumors (GH-PitNET) is the somatostatin receptor type 2 (SST2). However, approximately half of patients treated with octreotide, an SST2 agonist, show a low response rate or are octreotide-resistant. Here we present mechanistic data that shows co-treatment with simufilam, a novel oral therapeutic candidate, enhances sensitivity to octreotide. We previously showed that the cytoskeleton protein...

Introduction: Bone mineral density (BMD) is considered a valid surrogate of bone strength in postmenopausal women, however it lacks sensitivity in individual fracture risk assessment in the setting of women with early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). Indeed, mechanical resistance of bone only partially depends on bone quantity, and bone geometry and size play an important role in bone resistance to fractures. In this cross-sectional study, ...

Introduction: To date, two pharmacogenetic studies investigated the effect of the common exon 3 deletion of GH receptor (d3-GHR) variant in small series of acromegalic patients treated with Pegvisomant (Peg), suggesting an association of d3-GHR allele with better response to Peg.Aim: To assess the influence of d3-GHR variant in a large cohort of acromegalics with active disease and resistance to somatostatin analogues (SSA) treated with either Peg monoth...

A common polymorphic variant of the GH receptor (exon-3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some, but not all, GH deficient (GHD) and non-GHD patients. Aim of this study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of short- and long-term rhGH therapy, with particular focus on glucose homeostasis (1 year: n=100 and 5 years: n=50). Effects of rhGH...

Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) are still orphan of medical therapy. The drmgs approved for the other types of PitNETs, e.g. somatostatin analogues (SSA) with high affinity for somatostatin receptors (SSTs) type 2 (SST2) and 5 (SST5) are poorly efficacious in NF-PitNETs. Among SSTs, NF-PitNETs express high levels of SST3, a receptor that can mediate antiproliferative and apoptotic signaling. ITF2984 is a pan-SST ligand with high affinity for SST3, ...

The bone strain index (BSI) is a marker of bone deformation based on a finite element analysis inferred from dual X-ray absorptiometry (DXA) scans, that has been proposed as a predictor of fractures in osteoporosis. BSI value represents the average equivalent strain in a skeletal site, assuming that a higher strain level (higher BSI) indicates a lower bone’s resistance to loads with consequent higher risk of fractures. BSI index is usually calculated for specific loading ...