Cushing syndrome.

Cushing syndrome (CS) is a constellation of signs and symptoms caused by excessive exposure to exogenous or endogenous glucocorticoid hormones. Endogenous CS is caused by increased cortisol production by one or both adrenal glands (adrenal CS) or by elevated adrenocorticotropic hormone (ACTH) secretion from a pituitary tumour (Cushing disease (CD)) or non-pituitary tumour (ectopic ACTH secretion), which stimulates excessive cortisol production. CS is associated with severe multisystem morbidity, including impaired cardiovascular and metabolic function, infections and neuropsychiatric disorders, which notably reduce quality of life.

Personalized Medicine in Acromegaly: The ACROFAST Study.

Context: Medical treatment of acromegaly is currently performed through a trial-and-error approach using first-generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response.

Objective: Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated.

Integrative clinical, hormonal, and molecular data associate with invasiveness in acromegaly: REMAH study.

Introduction: Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management.

Cushing's Syndrome in the Elderly.

Management of Cushing's syndrome (CS) can be particularly challenging in older patients, compared with younger individuals, due to the lack of several clinical features associated with cortisol excess along with a greater burden of associated comorbidities. Moreover, the interpretation of diagnostic tests could be influenced by age-related physiological changes in cortisol secretion. While mortality is higher and quality of life is more impaired in the elderly with CS as compared with the younger, there is currently no agreement on the most effective therapeutic options in aged individuals, and safety data concerning medical treatment are scanty.

The thrombotic risk in Cushing's syndrome-questions, answers, and the algorithm to consider in its assessment: part I-thrombotic risk not related to surgery.

Introduction: Recently, it has been reported that there is a great diversity in strategies used for thromboprophylaxis in patients with Cushing's syndrome (CS). An aim of this review was to discuss these practices in light of the existing data on the thrombotic risk in patients with CS and guidelines for medically ill patients.

Methods: The four relevant topics and questions on thrombotic risk in CS were identified.

Evaluation of bone-related mechanical properties in female patients with long-term remission of Cushing's syndrome using quantitative computed tomography-based finite element analysis.

Background: Hypercortisolism in Cushing's syndrome (CS) is associated with bone loss, skeletal fragility, and altered bone quality. No studies evaluated bone geometric and strain-stress values in CS patients after remission thus far.

Patients And Methods: Thirty-two women with CS in remission (mean age [±SD] 51 ± 11; body mass index [BMI], 27 ± 4 kg/m2; mean time of remission, 120 ± 90 months) and 32 age-, BMI-, and gonadal status-matched female controls.

New molecular tools for precision medicine in pituitary neuroendocrine tumors.

Precision, personalized, or individualized medicine in pituitary neuroendocrine tumors (PitNETs) has become a major topic in the last few years. It is based on the use of biomarkers that predictively segregate patients and give answers to clinically relevant questions that help us in the individualization of their management. It allows us to make early diagnosis, predict response to medical treatments, predict surgical outcomes and investigate new targets for therapeutic molecules.

High prevalence of venous thrombotic events in Cushing's syndrome: data from ERCUSYN and details in relation to surgery.

Objective: The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in patients included in the European Registry on Cushing's syndrome (ERCUSYN), compare their clinical characteristics with those who did not develop VTE and identify risk factors for VTE.

Design: A retrospective observational cohort study.

Methods: Data extraction from the registry was taken on February, 7, 2022.

Magnetic resonance imaging as a predictor of therapeutic response to pasireotide in acromegaly.

Objective: Hyperintensity signal in T2-weighted magnetic resonance imaging (MRI) has been related to better therapeutic response during pasireotide treatment in acromegaly. The aim of the study was to evaluate T2 MRI signal intensity and its relation with pasireotide therapeutic effectiveness in real-life clinical practice.

Design, Patients And Measurements: Retrospective multicentre study including acromegaly patients treated with pasireotide.

Gut microbial dysbiosis in patients with Cushing's disease in long-term remission. Relationship with cardiometabolic risk.

Background: Patients with Cushing's disease (CD) in remission maintain an increased cardiovascular risk. Impaired characteristics of gut microbiome (dysbiosis) have been associated with several cardiometabolic risk factors.

Methods: Twenty-eight female non-diabetic patients with CD in remission with a mean ± SD) age of 51 ± 9 years, mean ( ± SD) BMI, 26 ± 4, median (IQR) duration of remission, 11(4) years and 24 gender-, age, BMI-matched controls were included.

Molecular characterization of epithelial-mesenchymal transition and medical treatment related-genes in non-functioning pituitary neuroendocrine tumors.

Introduction: Different medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas.

Cushing's syndrome in the elderly: data from the European Registry on Cushing's syndrome.

Objective: To evaluate whether age-related differences exist in clinical characteristics, diagnostic approach, and management strategies in patients with Cushing's syndrome (CS) included in the European Registry on Cushing's Syndrome (ERCUSYN).

Design: Cohort study.

Methods: We analyzed 1791 patients with CS, of whom 1234 (69%) had pituitary-dependent CS (PIT-CS), 450 (25%) adrenal-dependent CS (ADR-CS), and 107 (6%) had an ectopic source (ECT-CS).

Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN.

Corticotroph tumor progression after bilateral adrenalectomy/Nelson's syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate the prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing's disease (CD) included in the European Registry on Cushing's Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX.

Clinical presentation and etiology of Cushing's syndrome: Data from ERCUSYN.

This review presents the data on clinical presentation at diagnosis in 1564 patients included in the European Registry on Cushing's syndrome (ERCUSYN), of whom 1045 (67%) had pituitary-dependent Cushing's syndrome (CS) (PIT-CS), 385 (25%) had adrenal dependent CS (ADR-CS) and 89 (5%) had ectopic adrenocorticotropic hormone syndrome (ECT-CS). The most frequent symptoms in the overall series were weight gain (83%), hypertension (79%), skin alterations (76%) and myopathy (70%). Diabetes mellitus was present in 32% and depression in 35% of patients.

Diagnosis and management of hypertension in patients with Cushing's syndrome: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension.

Endogenous/exogenous Cushing's syndrome is characterized by a cluster of systemic manifestations of hypercortisolism, which cause increased cardiovascular risk. Its biological basis is glucocorticoid excess, acting on various pathogenic processes inducing cardiovascular damage. Hypertension is a common feature in Cushing's syndrome and may persist after normalizing hormone excess and discontinuing steroid therapy.

Unmet needs in Cushing's syndrome: the patients' perspective.

Background: Cushing's syndrome (CS) is a rare condition of chronically elevated cortisol levels resulting in diverse comorbidities, many of which endure beyond successful treatment affecting the quality of life. Few data are available concerning patients' experiences of diagnosis, care and persistent comorbidities.

Objective: To assess CS patients' perspectives on the diagnostic and care journey to identify unmet therapeutic needs.

Quality of life impairment after a diagnosis of Cushing's syndrome.

This brief review is devoted mainly to publications in the last 5 years dealing with health-related quality of life (QoL) after a diagnosis of endogenous hypercortisolism, due to pituitary-dependent Cushing's disease (CD) or any other cause of Cushing syndrome (CS). Despite improvement after treatment, persistent physical morbidity, neurocognitive problems like worse executive capacity and memory as well as stress intolerance, depressive symptoms and more anxiety, lead to long-term impairment of QoL.

Data mining analyses for precision medicine in acromegaly: a proof of concept.

Predicting which acromegaly patients could benefit from somatostatin receptor ligands (SRL) is a must for personalized medicine. Although many biomarkers linked to SRL response have been identified, there is no consensus criterion on how to assign this pharmacologic treatment according to biomarker levels. Our aim is to provide better predictive tools for an accurate acromegaly patient stratification regarding the ability to respond to SRL.

Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response.

Acromegaly is caused by excess growth hormone (GH) produced by a pituitary tumor. First-generation somatostatin receptor ligands (SRLs) are the first-line treatment. Several studies have linked E-cadherin loss and epithelial-mesenchymal transition (EMT) with resistance to SRLs.

Consensus on diagnosis and management of Cushing's disease: a guideline update.

Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants.