0000000000086509
AUTHOR
Annamaria Colao
Uterine effects of metformin administration in anovulatory women with polycystic ovary sindrome
Background Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome (PCOS), inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages. The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin. Methods Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age- and body mass index-matched healthy women (control group) were studied. PCOS patients were treated with metformin (850 mg twice daily) for 6 months, whereas the control group did not receive any treatment. In these PCOS patients who ovulated whil…
Everolimus as first line therapy for pancreatic neuroendocrine tumours: current knowledge and future perspectives
urpose Everolimus has been shown to be effective for advanced pancreatic neuroendocrine tumours (pNETs), but its positioning in the therapeutic algorithm for pNETs is matter of debate. Methods With the aim to shed light on this point, we performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies, and the recommendations of international guidelines. In addition, we performed an extensive search on the Clinical Trial Registries databases worldwide, to gather information on the ongoing clinical trials related to this specific topic. Results We identified eight retrospective published studies, two prospective published studies…
Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome
Abstract Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PC…
Predictive factors of response to mTOR inhibitors in neuroendocrine tumours
Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for th…
Alteration of the growth hormone axis, visceral fat dysfunction, and early cardiometabolic risk in adults: the role of the visceral adiposity index
The aim of the study is to clarify the relationship between adipose tissue dysfunction, metabolic profile and growth hormone (GH)/insulin-like growth factor (IGF)-I secretion in healthy adult subjects. We investigated the metabolic profile in a cohort of 231 consecutive healthy subjects in relation to GH, IGF-I levels, and visceral adiposity index (VAI). Anthropometric measures, lipid profile, and glucose and insulin levels during oral glucose tolerance test, Homa-IR and ISI Matsuda, IGF-I and GH peak after GHRH plus Arginine test were analyzed. The subjects with high VAI showed lower GH peak (22.8 ± 11.1 vs. 42.2 ± 21.3 µg/L; p = 0.049) and lower IGF-I (presented as IGF-I under normal rang…
Corticosteroids in oncology: Use, overuse, indications, contraindications. An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper
Corticosteroids (CSs) are widely used in oncology, presenting several different indications. They are useful for induction of apoptosis in hematological neoplasms, for management of anaphylaxis and cytokine release/hypersensitivity reaction and for the symptomatic treatment of many tumour- and treatment-related complications. If the employment of CSs in the oncological setting results in several benefits for patients and satisfaction for clinicians, on the other hand, many potential adverse events (AEs), both during treatment and after withdrawal of CSs, as well as the duality of the effects of these compounds in oncology, recommend being cautious in clinical practice. To date, several gray…
Efficacy and safety of everolimus in extrapancreatic neuroendocrine tumor: a comprehensive review of literature
BACKGROUND Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PATIENTS AND METHODS A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary. RESULTS The present study included 22 different publications, including 874 patients and 4…
The degree of urinary hypercortisolism is not correlated with the severity of cushing’s syndrome
Cushing syndrome (CS) is characterized by increased morbidity and mortality compared to the general population. However, there are patients who have more clinical aggressive forms than others. Aim of the study is to evaluate whether the degree of hypercortisolism, defined by the number of times urinary free cortisol (UFC) levels exceed the upper limit of the normal range (ULN), is related to the worsening of phenotypic features, as well as metabolic and cardiovascular parameters, in a cohort of CS patients. A cross-sectional study was conducted on 192 patients with active CS, consecutively presenting at the outpatients' clinic of the University Hospitals of Ancona, Naples, and Palermo. Pati…
Effect of Cabergoline on Metabolism in Prolactinomas.
<b><i>Introduction:</i></b> Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. <b><i>Patients and Methods:</i></b> 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuo…
Clinical and metabolic effects of first-line treatment with somatostatin analogues or surgery in acromegaly: a retrospective and comparative study.
To evaluate the metabolic effects of first-line somatostatin analogues or surgery in acromegaly. Retrospective, comparative, 12-month follow-up. Two hundred and thirty one patients (123 men, age 47.32 ± 14.63 years) with active acromegaly, first line treatments were somatostatin analogues in 151 (65.4%) and surgery in 80 (34.6%). Metabolic syndrome (MS) parameters, glucose, insulin and GH during oral glucose tolerance test, stimulated insulin sensitivity by insulin sensitivity index (ISI Matsuda), early and total insulin-secretion rate by insulinogenic index and AUC(INS), visceral adiposity function, expressed by visceral adipose index (VAI). Somatostatin analogues treatment improved all MS…
Nonconventional Doses of Somatostatin Analogs in Patients With Progressing Well-Differentiated Neuroendocrine Tumor
Abstract Purpose To evaluate the antiproliferative activity and safety of nonconventional high doses of somatostatin analogs (HD-SSA) in patients with well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NET) with radiological disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria on a previous treatment. Methods A retrospective analysis of prospectively maintained databases from 13 Italian NET-dedicated centers was performed. Main inclusion criteria were: well-differentiated G1 or G2 GEP-NET, progressive disease on a previous treatment, and subsequent treatment with HD-SSA (either by increased administered dose [dose intensity] or…
Is diabetes in Cushing's syndrome only a consequence of hypercortisolism?
ObjectiveDiabetes mellitus (DM) is one of the most frequent complications of Cushing's syndrome (CS). The aim of this study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients.DesignCross-sectional study on 140 patients with CS.MethodsA total of 113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 years) and 27 men (19 with pituitary disease and eight with adrenal disease, aged 38.1±20.01 years) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes), and diabe…
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. Hormonal, clinical and metabolic parameters were measured at baseline and at 3-month and 6-month follow-up, whereas tumour size was evaluated at baseline and at 6-mont…
A rare rarity: neuroendocrine tumor of the esophagus
Abstract Esophageal Neuroendocrine tumors (NETs) are rare, aggressive and lacking specific symptoms. This causes a diagnostic delay, worsening the prognosis. Numerous cases are reported in literature, without a consensus on the management. Our aim was to clarify epidemiology, clinical presentation, diagnostic, therapeutic management of esophageal NETs. Extensive literature search identified a total of 226 articles. One hundred twenty-five articles (n = 1676) met the inclusion criteria, showing that: the incidence of esophageal NET varies geographically; men (60–70 years) are more affected; smoking and alcohol abuse are the major risk factors; dysphagia, weight loss, appetite loss are the mo…
Metabolic and cardiopulmonary effects of detraining after a structured exercise training programme in young PCOS women
Summary Objective The aim of the present study was to determine if the favourable cardiopulmonary and metabolic benefits induced by exercise training (ET) programme are maintained after its cessation. Patients Thirty-two young overweight polycystic ovary syndrome (PCOS) women matched for age and body mass index (BMI) with other 32 PCOS patients was enrolled. The first group [PCOS-T (trained)] underwent 24-week ET programme, whereas the second [PCOS-DT (detrained)] underwent 12-week ET programme followed by 12-week detraining period. Methods At baseline, after 12- and 24-week follow-up, all PCOS women were studied for their hormonal (ovarian and adrenal androgens), metabolic (glucose and …
Uterine effects of clomiphene citrate in women with polycystic ovary syndrome: a prospective controlled study
Background Previous data on the efficacy of clomiphene citrate, the most commonly used drug for treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS), have shown a discrepancy between ovulation and pregnancy rates. In the present subanalysis (of a larger previously published randomized controlled trial), the effect of clomiphene citrate on several ultrasonographic markers of uterine receptivity in PCOS patients who ovulated under treatment was studied. Methods Thirty-three PCOS women who ovulated under 150 mg daily clomiphene citrate and 33 healthy controls were studied. Uterine, subendometrial and endometrial blood flows, endometrial thickness and pattern were …
Lanreotide Therapy vs Active Surveillance in MEN1-Related Pancreatic Neuroendocrine Tumors2 Centimeters.
Abstract Purpose Pancreatic neuroendocrine tumors (pNETs) are frequent in multiple endocrine neoplasia type 1 (MEN1) syndrome. They are usually not surgically treated unless larger than 1 to 2 cm or a growth rate &gt; 0.5 cm per year. Somatostatin analogues represent one of the main therapeutic options in pNETs, but they have never been prospectively investigated in MEN1-related pNETs. The aim of this study was to prospectively evaluate the effectiveness of lanreotide in patients with MEN1-related pNETs &lt; 2 cm. Methods MEN1 patients with 1 or more pNETs &lt; 2 cm of maximal diameter were considered. Study design was prospective observational, comparing patients treated with l…
Neuroendocrine Tumors: A Comprehensive Review on Nutritional Approaches.
Simple Summary Neuroendocrine neoplasms and their main subtype neuroendocrine tumors have an increasing incidence worldwide, associated with a high survival and prevalence rate. Both the tumor itself and systemic therapy can have an impact on patients' nutrition. Conversely, preliminary data suggest that malnutrition has a negative impact on the development and prognosis of neuroendocrine tumors, as does obesity. The aim of this review is to condense the latest evidence on the role of the most widely used dietary patterns, the Mediterranean diet, the ketogenic diet and intermittent fasting, in the context of neuroendocrine tumors. Nutritional plans are an integral part of the multidisciplin…
Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers
BackgroundHypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare.Case SeriesThe present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA)…
From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?
AbstractGut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microb…
The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the treatment of the gastrinoma?
Purpose: Analyze the role of somatostatin analogues (SSAs) in the treatment of sporadic and MEN1-related gastrinomas, trying to define whether recent trials have changed the landscape of gastrinoma therapy. Methods: We evaluate the rationale of SSA use in the treatment of gastrinomas, summarize the current literature concerning the effect of SSAs on the control of Zollinger-Ellison syndrome (ZES) and gastrinomas tumor progression and discuss their role in the most recent guidelines. Results: The medical treatment of gastrinoma and related ZES is aimed at controlling acid hypersecretion and tumor progression, in inoperable patients. The use of proton pump inhibitors (PPIs) to control the syn…
Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group
Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 ga…