Endocrine Abstracts

Introduction: In patients with ACTH-dependent hypercortisolism, the corticotropin-releasing-hormone (CRH) test and the high dose dexamethasone suppression test (HDDST) can be used to differentiate between pituitary ACTH production (Cushing’s disease) and ectopic ACTH production. The rationale is that a pituitary adenoma will show some response to CRH and ACTH whereas an ectopic source is less responsive to ACTH and CRH. However, there is discussion about the clinical util...

Background: Functioning (FCA) and silent corticotroph (SCA) pituitary adenomas act differently from a clinical perspective, despite both subtypes showing positive ACTH staining by immunohistochemistry. They are challenging to treat, the former due to functional ACTH production and consequently hypercortisolemia leading to Cushing disease, whereas the latter due to invasive and recurrent behaviour. Moreover, the molecular mechanisms behind their distinct behaviour are not clear...

Introduction: Immune-check point inhibitors (ICPis) has been shown to significantly improve survival in patients with advanced melanoma. Immune-related endocrinopathies (irEs) and in particular hypophysitis and thyroid dysfunction have been well described with an incidence varying from 9–17% and 3.8–13.2% respectively.Methods: This is a retrospective analysis of irEs in 325 (190 men) patients with melanoma receiving ICPis (PD-1/PDL-1 or CTLA-4 ...

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...

Introduction: Compared with healthy controls, women with Cushing’s syndrome (CS) in long-term remission have reduced functional brain responses during episodic and working memory testing and decreased overall levels of DNA methylation in blood cells. Here, we sought to test the hypothesis that functional brain responses in the prefrontal cortex and hippocampus are related to epigenetic changes in subjects with CS in long-term remission.Methods: In t...

Background: According to the Endocrine Society’s guidelines, the screening and diagnosis of Cushing’s syndrome (CS) are based on the results of the overnight dexamethasone suppression test (DST), midnight salivary cortisol and 24-hour urinary free cortisol (UFC) measurements. These 3 tests reflect cortisol levels at the time of sampling without providing retrospective information. Hair cortisol concentration is a non-invasive way to measure cortisol exposure over lon...

Background: Muscle weakness may persist in patients with Cushing’s syndrome (CS) long-term after resolution of hypercortisolism, but mechanisms determining this sustained impairment are not known. We hypothesized that alteration of muscle structure, due to fatty infiltration, is associated with muscle dysfunctions in these patients.Patients & methods: Twenty-six CS women [mean(±S.D.) age 49±12 years; mean(±S....

Background: Detection of MRI-negative ACTH-producing pituitary adenomas is a challenge in the management of patients with Cushing’s disease. There are some data on the possibility of pituitary adenomas to accumulate 18F-fluorodeoxyglucose (18F-FDG) during the 18F-FDG positron emission tomography and computer tomography (18F-FDG PET/CT).Aim: To study the potential of brain 18F-fluorodeoxyglucose PET/CT for localization of MRI-negative ACTH-producing ...

Cushing’s disease tumours bear activating mutations in the ubiquitin-specific-protease 8 gene (USP8) gene in 40-60% of cases. We have previously observed that patients with USP8 mutant tumours have smaller tumour size and show a better response to high dose (8mg) dexamethasone stimulation test compared to those with wild type USP8 (1). The aim of this study was to define the role of USP8 on glucocorticoid receptor (GR) in corticotroph tumour cells. We did experim...

Introduction: Osilodrostat is a potent oral 11β-hydroxylase inhibitor currently in Phase III clinical development for the treatment of Cushing’s syndrome (CS). The key pharmacokinetic (PK) properties, drug–drug interactions (DDIs), and population PK findings for osilodrostat in humans are summarized.Methods: Osilodrostat PK has been characterized in nine Phase I studies (healthy subjects and subjects with hepatic or renal impairment), two ...

Introduction: Pasireotide (PAS) is an effective treatment for Cushing’s disease (CD) but its use is burdened by the high incidence of diabetes mellitus (DM). We aimed to evaluate the effect of a single subcutaneous injection of PAS on glucose metabolism in CD patients, to identify factors predicting rapid deterioration of glycaemic control.Methods: 14 patients [(f/m=12/2, mean age 43±11.3 years, follow-up 17 months (2-63)] with CD treated with ...

Chronic hypercortisolism is associated with dramatic increase in fragility fractures. The evaluation of skeletal fragility in Cushing’s syndrome (CS) is a clinical challenge, since fractures may occur even in presence of normal bone mineral density (BMD). Recently, measurement of bone marrow fat (BMF) by vertebral magnetic resonance spectroscopy (MRS) was proposed as alternative tool for evaluating skeletal fragility in primary and secondary osteoporosis. Noteworthy, rece...