Endocrine Abstracts

BackgroundWe provided the first description of thyrotoxicosis due to atypical thyroiditis in patients hospitalised for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic disease (Covid-19), not associated with neck pain, more common in men, correlated with disease severity and coexisting with non-thyroidal illness syndrome. Classic viral subacute thyroiditis is often followed by permanent thyroid dysfunction and autoimmunity, thus we h...

Objectives: Dysthyroid Optic Neuropathy (DON) is a severe complication of Graves’ Orbitopathy (GO), requiring prompt treatment. First line treatment is high dose intravenous steroids, then surgery is considered mandatory. We studied the clinical outcomes of surgery for DON, with and without previous therapy with steroids.Methods: 88 orbits of 56 patients with DON were treated with surgical orbital decompression. 33 orbits (37.5 %) underwent surgery ...

Background: Severe congenital growth hormone deficiency (cGHD) is a rare but potentially life-threatening condition. Even though random growth hormone (GH) can confirm cGHD during the first week of life, the diagnosis remains extremely challenging in the absence of reliable reference values in healthy neonates and thus of a best diagnostic cut-off.Aims: First, to provide solid reference values for GH concentrations in term newborns, by means of a non-inv...

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...

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...

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...

The majority of adrenocortical carcinomas (ACC) overexpress insulin-like growth factor 2 (IGF2). Although IGF2 drives a proliferative autocrine loop by binding to IGF1R and the isoform A of the insulin receptor (IRA), most studies focused on IGF1R. Recently, a high expression of IRA was observed in ACC vs normal adrenal tissues (NA), suggesting its potential involvement in modulating IGF2 effects in adrenocortical tumorigenesis. Aim of this study was to investigate the specifi...