Endocrine Abstracts

Pasireotide (SOM230) is a multireceptor ligand somatostatin analogue with high binding affinity to somatostatin receptor subtype 5, which is predominantly expressed in ACTH-secreting pituitary adenomas. It is indicated for the treatment of adult patients with Cushing’s disease (CD) for whom pituitary surgery is not an option or has not been curative. Our study evaluated the effects of pasireotide, administered for 12 months at a dose of 600–900 μg/daily, in five...

Patients with Cushing’s syndrome have a poor quality of sleep. However, little is known about their timing of sleep as regulated by the circadian clock, the so called-chronotype. Considering that patients with Cushing’s syndrome lose their rhythmic circadian cortisol secretion and that corticosteroids act as synchronizer of the circadian clock in cells, aim of the study was to determine whether patients with Cushing’s syndrome alter the timing of their sleep com...

Background: Cyclic Cushing’s syndrome (cCS) is a sub-entity of Cushing’s syndrome (CS) associated with diagnostic and therapeutic challenges. It describes a condition, in which phases of clear-cut biochemical hypercortisolism are followed by spontaneous troughs of normal or subnormal cortisol secretion. We conducted the first systematic literature review to identify common features of cCS.Methods: We searched MEDLINE (via PubMed) for eligible s...

Corticotrophin-releasing hormone (CRH) stimulation test is used in the differential diagnosis of Cushing’s syndrome. Cushing’s disease tumours carry somatic driver activating mutations in the ubiquitin-specific-protease 8 (USP8) gene in almost half of the cases. The aim of the present study was to examine whether the USP8 mutational status in Cushing’s disease tumours influences the response to the CRH stimulation test. We did a monocentric, re...

The tumorigenesis of Cushing’s disease is characterized by somatic mutations in the USP8 gene in almost half of the cases. USP8 encodes for ubiquitin specific protease 8, a deubiquitinase that rescues proteins involved in the regulation of ACTH synthesis in corticotroph cells. In the present study we tested the antisecretory and antiproliferative efficacy of a commercially available specific USP8 inhibitor (IC50 3.1 μM USP8; >90 μM USP7) in immortalized muri...

: Patients with Cushing’s disease (CD) have increased cardiovascular risk due to metabolic alterations caused by glucocorticoids excess. Pasireotide, a multireceptor-targeted somatostatin analogue, is a therapeutic option in CD patients in whom surgery is not curative or not feasible. Pasireotide has been shown to be effective in controlling hypercortisolism and to improve metabolic features. Recently, the visceral adiposity index (VAI) has been proposed as a marker of vi...

Introduction: CyberKnife (CK) is an emerging treatment for pituitary tumours (PT) resistant to other therapies.Patients and methods: We report long-term CK effect on endocrine function and tumour volume in 20 PT patients (11M/10F, mean age 58.6±14.4years). Twelve patients harboured a non functioning adenoma, 2 an ACTH, 5 a GH (one case of TSH co-secretion) and 2 a PRL-secreting PT. Before CK nine patients had normal while 11 presented impaired pitui...

The somatostatin analogue pasireotide is approved for the treatment of Cushing’s disease, where it achieves biochemical normalization in ~40% of patients. Predicting pasireotide resistance would help avoid unnecessary treatment. Pasireotide mediates its antisecretory action by binding to somatostatin receptor 5 (SSTR5). Almost half of corticotroph tumours carry mutations in the ubiquitin specific protease 8 (USP8) gene that encodes for a deubiquitinase. Pre...

A recent phase III clinical trial has demonstrated that the treatment with the somatostatin analogue pasireotide normalizes cortisol secretion in 15–28% of patients with Cushing’s disease (CD). The aim of the current study was to evaluate the effectiveness of 6-months pasireotide treatment on clinical and hormonal profiles in a group of CD patients with mild to moderate disease according with the real-word evidence. Thirty-two patients with CD unsuccessfully treated ...

IntroductionSomatic USP8 mutations are found in around 50% of Cushing’s disease tumours and are located in a single mutational hotspot that contains the recognition site for 14–3-3. These proteins bind to phosphoserine recognition motifs to alter the function and location of their target proteins, and are deregulated in several cancers. AimTo explore the expression and function of 14–3-3 prot...