Is pasireotide-induced diabetes mellitus predictable? A pilot study on the effect of a single dose of pasireotide on glucose homeostasis.

Introduction: Pasireotide (PAS) is an effective treatment for Cushing's disease (CD) but its use is burdened by an associated high incidence of diabetes mellitus (DM). The aim of this study was to examine the effect of a single subcutaneous injection of PAS on glucose metabolism in CD, and to identify predictors of DM onset.

Methods: Fifteen patients with CD (13 females, 2 males; median age 43 years [IQR 34-50]) were submitted to an acute PAS test (600 µg s.

Cushing's syndrome: Overview of clinical presentation, diagnostic tools and complications.

Cushing's syndrome (CS) is a severe condition that results from chronic exposure to elevated circulating cortisol levels; it is a rare but potentially life-threating condition, especially when not timely diagnosed and treated. Even though the diagnosis can be straightforward in florid cases due to their typical phenotype, milder forms can be missed. Despite the availability of different screening tests, the diagnosis remains challenging as none of the available tools proved to be fully accurate.

Approach to patients with pseudo-Cushing's states.

The distinction between pseudo-Cushing's states (PCS) and Cushing's syndrome (CS) poses a significant clinical challenge even for expert endocrinologists. A patient's clinical history can sometimes help to distinguish between them (as in the case of alcoholic individuals), but the overlap in clinical and laboratory findings makes it difficult to arrive at a definitive diagnosis. We aim to describe the most common situations that can give rise to a condition resembling overt endogenous hypercortisolism and try to answer questions that physicians often face in clinical practice.

The medical treatment with pasireotide in Cushing's disease: an Italian multicentre experience based on "real-world evidence".

A phase III study has demonstrated that 6-month pasireotide treatment induced disease control with good safety in 15-26% of patients with Cushing's disease (CD). The aim of the current study was to evaluate the 6-month efficacy and safety of pasireotide treatment according to the real-world evidence. Thirty-two CD patients started pasireotide at the dose of 600 µg twice a day (bid) and with the chance of up-titration to 900 µg bid, or down-titration to 450 or 300 µg bid, on the basis of urinary cortisol (UC) levels or safety.

Metyrapone treatment in Cushing's syndrome: a real-life study.

Introduction And Aim: Medical treatment is increasingly used in patients with Cushing's syndrome (CS). Metyrapone (MET) is an inhibitor of 11β-hydroxylase: retrospective studies reported a decrease of cortisol secretion in 50% of cases. We evaluated the effectiveness of MET in an observational study, considering the normalization of urinary-free cortisol (UFC) and late-night salivary cortisol (LNSC) levels.

Effects of pasireotide treatment on coagulative profile: a prospective study in patients with Cushing's disease.

Introduction: Cushing's disease (CD) is characterized by procoagulative profile. Treatment with cortisol-reducing medications might normalize the coagulation impairment potentially eliminating the risk of thromboembolic complications.

Aim: The aim of this prospective study is to evaluate the effectiveness of 6-12 months of treatment with pasireotide (Signifor®, Novartis) 600 µg twice daily on coagulative factors in 21 patients (16 females, mean age 46 ± 12.

Cardiovascular autonomic dysfunction in patients with idiopathic diabetes insipidus.

Introduction: Central diabetes insipidus (DI) is a rare disease characterized by the excretion of excessive volumes of dilute urine due to reduced levels of the antidiuretic hormone arginine vasopressin (AVP), caused by an acquired or genetic defect in the neurohypophysis. The aim of this study was to identify any autonomic dysfunction (AD) in patients with DI as a possible cofactor responsible for their reportedly higher mortality.

Methods: The study involved 12 patients (6 females) with central idiopathic DI and a well-controlled electrolyte balance, and 12 controls matched for age, sex and cardiovascular risk factors, who were assessed using the tilt, lying-to-standing, hand grip, deep breath, Valsalva maneuver and Stroop tests.

Daily salivary cortisol and cortisone rhythm in patients with adrenal incidentaloma.

Background And Aim: Impaired cortisol rhythm is a characteristic feature of Cushing's Syndrome, nevertheless late night salivary cortisol (LNSC) is not suitable to detect subclinical hypercortisolism in patients with adrenal incidentaloma (AI). We studied daily salivary cortisol (F) and cortisone (E) rhythm in patients with AI.

Materials And Methods: Six saliva samples were collected from awakening to night in 106 patients with AI and 40 controls.

Body Composition is Different After Surgical or Pharmacological Remission of Cushing's Syndrome: A Prospective DXA Study.

Patients with active Cushing's syndrome (CS) exhibit an increase of the visceral adipose tissue, increasing the risk of cardiovascular events. Until now, it is not yet clear whether remission of CS leads to a normalization of body composition, or if different strategies to control hypercortisolism could result in a different clinical outcome concerning adipose tissue distribution. Therefore, we analyzed body composition changes using dual-energy X-ray absorptiometry (DXA) in patients with CS in a prospective and controlled study.

Glucose Metabolism Abnormalities in Cushing Syndrome: From Molecular Basis to Clinical Management.

An impaired glucose metabolism, which often leads to the onset of diabetes mellitus (DM), is a common complication of chronic exposure to exogenous and endogenous glucocorticoid (GC) excess and plays an important part in contributing to morbidity and mortality in patients with Cushing syndrome (CS). This article reviews the pathogenesis, epidemiology, diagnosis, and management of changes in glucose metabolism associated with hypercortisolism, addressing both the pathophysiological aspects and the clinical and therapeutic implications. Chronic hypercortisolism may have pleiotropic effects on all major peripheral tissues governing glucose homeostasis.

Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.

Introduction: Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion.

Materials And Methods: Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test.

Results: Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.

Long-term glucocorticoid effect on bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Introduction: Patients with 21-hydroxylase deficiency (21OHD) assume a lifelong glucocorticoid (GC) therapy. Excessive GC treatment increases the risk of osteoporosis and bone fractures, even though the role of substitutive therapy is not fully established: we analyzed the effect of GC dose on bone metabolism and bone mineral density (BMD) over time in patients with 21OHD.

Methods: We studied bone metabolism markers and BMD in 38 adult patients with 21OHD (19-47 years, 24 females and 14 males) and 38 matched healthy control.

Screening Tests for Cushing's Syndrome: Urinary Free Cortisol Role Measured by LC-MS/MS.

Introduction And Aim: As initial screening for Cushing's syndrome (CS), The Endocrine Society guidelines recommend one of the following: the 1-mg dexamethasone suppression test (DST) or late-night salivary cortisol (LNSC) or urinary free cortisol (UFC) measurement. We examined the diagnostic performance of the above-mentioned tests in a series of patients.

Materials And Methods: We retrospectively analyzed 137 patients with clinical conditions suggestive of hypercortisolism: 38 with confirmed CS diagnosis and 99 without (termed non-CS).

Age and the metabolic syndrome affect salivary cortisol rhythm: data from a community sample.

Objective: Measurement of cortisol levels in saliva is a marker of free hormone. How salivary cortisol rhythm is affected by age, gender, the metabolic syndrome and estrogen-progestin therapy was evaluated in a community sample of adults.

Subjects And Methods: One hundred twenty volunteers recruited from the Hospital staff and family members of the Endocrinology Unit were instructed to collect 7 salivary samples: the first on awakening (F(0)) and 6 more (F(1.

A venous thromboembolism risk assessment model for patients with Cushing's syndrome.

Cushing's syndrome (CS) is associated with an incidence of venous thromboembolism (VTE) about ten times higher than in the normal population. The aim of our study was to develop a model for identifying CS patients at higher risk of VTE. We considered clinical, hormonal, and coagulation data from 176 active CS patients and used a forward stepwise logistic multivariate regression analysis to select the major independent risk factors for thrombosis.

Perioperative thromboprophylaxis in Cushing's disease: What we did and what we are doing?

Purpose: Cushing's disease (CD) is associated with an increased risk of thrombotic events, particularly after surgery. No guidelines are available on the management of patients with CD undergoing pituitary transsphenoidal surgery (TSS). We aimed to compare the effectiveness of different prophylactic procedures on the prevention of thrombotic events after surgery in CD.

The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC-MS/MS method in routine clinical practice.

Objective: The Endocrine Society Clinical Guidelines recommend measuring 24-h urinary free cortisol (UFF) levels using a highly accurate method as one of the first-line screening tests for the diagnosis of Cushing's Syndrome (CS). We evaluated the performance of UFF, urinary free cortisone (UFE), and the UFF:UFE ratio, measured using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.

Subjects And Methods: The LC-MS/MS was used to analyze UFF and UFE levels in 43 surgically confirmed CS patients: 26 with Cushing's disease (CD, 16 de novo and ten recurrences), 11 with adrenal CS and six with ectopic CS; 22 CD patients in remission; 14 eu-cortisolemic CD patients receiving medical therapy; 60 non-CS patients; and 70 healthy controls.

Performance of salivary cortisol in the diagnosis of Cushing's syndrome, adrenal incidentaloma, and adrenal insufficiency.

Objective: Salivary cortisol has recently been suggested for studies on the hypothalamic-pituitary-adrenal (HPA) axis. The lack of circadian rhythm is a marker of Cushing's syndrome (CS), and some authors have reported that low salivary cortisol levels may be a marker of adrenal insufficiency. The aim of our study was to define the role of salivary cortisol in specific diagnostic settings of HPA axis disease.