Endocrine Abstracts

Dopamine agonist cabergoline (CB) is the first-choice treatment in prolactin-secreting adenomas (PRL-omas). It is effective in reducing PRL secretion and tumour size in about 90% of patients by binding dopamine D2 receptor (DRD2). Although no mutations in DRD2 were found, it has been reported that several polymorphisms of this locus associate with alcoholism and schizophrenia, diseases in which dopaminergic system plays an important role. To assess the possible asso...

Somatic mutations in splicing factor 3 subunit B1 (SF3B1) were found in about 20% of PRL-secreting PitNETs. SF3B1 is involved in pre-mRNA splicing and required for assembly of the U2 complex, which is critical for branch site recognition and the early stages of spliceosome assembly. Patients with mutant prolactinomas showed higher PRL levels and shorter progression-free survival compared to wild-type patients. Aims of the present study were: 1) to characterize the genetic prof...

Adrenocortical carcinomas (ACCs) are rare endocrine tumors with poor prognosis. They overexpress the insulin-like growth factor 2 (IGF2), that drives a proliferative autocrine loop by binding to IGF1R and IR. The majority of studies focused on IGF1R as mediator of IGF2 biological effects, but recently a high expression of IR, in particular of the isoform A, was observed in most ACCs, suggesting a potential role of this receptor in modulating IGF2 effects in adrenocortical tumo...

Objective: The diagnosis of central hypoadrenalism (HPAI) is a major clinical challenge. The gold standard procedure remains insuline tolerance test (ITT). Liquid chromatography tandem mass spectrometry (LC-MS/MS) is considered the best procedure for the evaluation of cortisol levels. This study aimed to evaluate cut-offs of serum (TM-SeC) and salivary cortisol (SaC) by LC-MS/MS and serum cortisol by ECLIA assay (E-SeC) after Standard dose ACTH test (SDCT) in diagnosing HPAI.<...

Introduction: A highly polymorphic microsatellite, comprising a variable length of a cytosine–adenosine (CA) repeat sequence, has been identified in the promoter region of IGF-I gene. The number of CA repeats ranges between 10 and 24 and the most common allele in the Caucasian population contains 19 CA (192 bp) repeats. Several studies investigated the relationship between this polymorphism and IGF-I levels, with conflicting results. Aim of this study was to investigate t...

Cushing’s Disease (CD) is a rare condition mostly caused by an ACTH-secreting pituitary tumor resulting in excess of cortisol release by the adrenal glands. Although pasireotide is the only pituitary-targeted drug approved to treat adult patients, many side effects are encountered during the clinical practice and a curative therapy for CD is still challenging. Recently, the discover of somatic mutations in the deubiquitinase USP8 gene in a subset of patients has ...

Cushing’s Disease (CD) is a rare condition characterized by an overproduction of ACTH by an ACTH-secreting pituitary tumor resulting in excess of cortisol release by the adrenal glands. Somatic mutations in the deubiquitinases USP8 and USP48, and in BRAF genes, have been reported in a subset of patients affected by CD. Aim of this study was to characterize the genetic profile of a cohort of 66 patients with ACTH-secreting tumors, searching for somatic mutations in USP8, U...

The cytoskeletal actin-binding protein filamin A (FLNA) is poorly expressed in adrenocortical carcinomas (ACC) compared to adenomas (ACA), and this might contribute to sustain the increased cell proliferation by downregulating IGF1R expression and its downstream signaling. In mouse neural progenitor cells, increased protein expression levels of the CDK1 kinase Wee1 have been found after loss of FLNA. This protein has a leading role in regulating the G2-M checkpoint and functio...

Adrenocortical carcinomas (ACC) are rare endocrine tumors that originate in the cortex of the adrenal gland. They are characterized by the overexpression of insulin-like growth factor 2 (IGF2), whose bond with two tyrosine-kinase receptors, IGF1R and IR, activates a cancer-promoting signalling cascade. Another component of the IGF system is mannose 6-phosphate/insulin-like growth factor 2 receptor (IGF2R), a scavenger receptor able to bind specifically IGF2. Its main role is t...

Background: Cortisol excess is associated with a higher prevalence of hypertension (Hy), type 2 diabetes (T2D) and fragility fractures (FX). A possible association between T2D and fragility FX with the degree of glucocorticoid (GC) suppression and peripheral activation or sensitivity even in non-hypercortisolemic subjects has been previously suggested.Aim: To assess if the degree of GC suppression or peripheral sensitivity and activation are associated w...