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Tosi F.,University of Verona | Fiers T.,Ghent University | Kaufman J.-M.,Ghent University | Dall'Alda M.,University of Verona | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2016

Context/Objective: Hyperandrogenism is a common feature of women with polycystic ovary syndrome (PCOS) and is considered a cardinal element for the diagnosis and phenotyping of this condition. Unfortunately, routinely available methods for measuring serum androgens suffer from major limitations.Nodata are available on the impact of androgen assay quality on the assignment of PCOS women to the different clinical phenotypes of PCOS, when defined accorDing to the Rotterdam criteria for diagnosis. Patients:Twohundred four consecutive Caucasianwomenwith PCOS, diagnosed by the Rotterdam criteria participated in the study. Design: Assessment of total T (TT), free T (FT),andandrostenedione (A) by both a chemiluminescent assay, routinely available in our hospital, and gold standard methodology, ie, liquid chromatography-mass spectrometry and equilibrium dialysis, was performed. The results were compared and the associations of these data with clinical and metabolic features of PCOS women were analyzed. Results: By using gold standard assays, TT was high in 36.3% of women, whereas A only marginally contributed to identifying hyperandrogenemic patients. However, gold standard FT measurement was elevated in 70.6% of the PCOS patients, identifying them as hyperandrogenemic. Routine TT and A assays, and the derived calculated FT, were strikingly inaccurate, with substantial overestimation. These assays erroneously classified 60 patients (29.4%), 32 as false hyperandrogenemic, and 28 as false normoandrogenemic, with incorrect assignment of many patients to the clinical phenotypes of PCOS and inappropriate estimation of their metabolic risk. In particular, women misclassified as normoandrogenic had amoresevere metabolic profile than true normoandrogenic subjects. Conclusions: FT alone, as measured by equilibrium dialysis or calculated by using the Vermeulen formula, provided that TT is assayed by gold standard methodology, can be used to identify hyperandrogenemic PCOS subjects. The use of routine androgen assays may misclassify the phenotype of many PCOS women, with errors in the estimation of individual metabolic risk.


Palmieri S.,Unit of Endocrinology and Metabolic Diseases | Palmieri S.,University of Milan | Eller-Vainicher C.,Unit of Endocrinology and Metabolic Diseases | Cairoli E.,Unit of Endocrinology and Metabolic Diseases | And 15 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: Hypercalciuria is frequently found in primary hyperparathyroidism (1HPT) and, although it generally normalizes after successful parathyroidectomy, may persist in some patients. The factors associated with persistent calcium renal leak (cRL) have not been clarified. Objective: The purpose of this study was to determine the prevalence of cRL in our 1HPT population and investigate cRL-related factors. Design: This was a retrospective longitudinal study. Setting: The study was conducted in an outpatient setting. Patients/Intervention: The participants were 95 patients with 1HPT successfully operated on who had a normal estimated glomerular filtration rate. Main Outcome Measures: The biochemical parameters of calcium metabolism and bone mineral density (BMD) measured by dual-X-ray absorptiometry before and 24 months after surgery were assessed. All histological findings were recorded. Results: Theprevalence of hypercalciuria beforeandafter surgerywas74%and32%,respectively. Before, surgerypatientswithcRLshowedlowercalciumandhigherphosphatelevelsthanthosewithoutcRL(10.9± 0.6 vs 11.4±0.8 mg/dL [2.7±0.2 vs 2.8±0.2 mmol/L], P<01 and 2.6±0.5 vs 2.4±0.4 mg/dL [0.84±0.2 vs 0.77±0.1 mmol/L], P=.04, respectively), whereas 24-h calciuria levels and the prevalence of 1HPT complications (osteoporosis, renal stones, and hypertension) were comparable. After surgery, serum calcium, phosphate,andPTHlevelswerecomparablebetweenpatientswithandwithoutcRL.Theprevalence ofthehistological findingofparathyroidhyperplasiawashigherin patientswithcRL(50%)thanin patients without cRL (22%) (P<01). The presence of cRL was independently associated with presurgery hypercalciuria( oddsratio,4.71;95%confidenceinterval,1.18-18.8;P<03)andparathyroidhyperplasia(oddsratio, 3.52;95%confidenceinterval,1.31-9.43;P<01).OnlypatientswithoutcRLhadimprovedBMDatthespine (P<04), total femur (P<01), and femoral neck (P<01). Conclusions: cRL is present in30%of patients with 1HPT after successful surgery, and it is associated with parathyroid hyperplasia before surgery and the lack of improvement in BMD after surgery. (J Clin Endocrinol Metab 100: 2734-2742, 2015 Copyright © 2015 by the Endocrine Society.


Morelli V.,University of Milan | Eller-Vainicher C.,Unit of Endocrinology and Metabolic Diseases | Palmieri S.,University of Milan | Cairoli E.,University of Milan | And 9 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2016

Context: Subtle hypercortisolism is associated with an increased risk of vertebral fracture (VFx). Objective: The objective was to determine the best parameters of cortisol secretion for detecting the VFx risk in patients with adrenal incidentalomas (AI). Design: This was a retrospective (cross-sectional arm) and prospective (longitudinal arm) design. In the cross-sectional arm, we assessed the accuracy of the cortisol secretion indexes in identifying the patients with VFx (prevalent VFx). In the longitudinal arm, we tested the cortisol secretion parameters, which were able to identify the prevalent VFx, for the prediction of the occurrence of a new VFx (incident VFx) in AI patients followed-up for at least 2 years. Setting: Four referral Italian endocrinology units participated in this study. Patients: A total of 444 and 126 AI patients without symptoms of hypercortisolism enrolled in the cross-sectional arm and longitudinal arm, respectively. Main Outcome Measures: Serum cortisol after a 1-mg dexamethasone suppression test (1 mg DST), urinary free cortisol, ACTH, bone mineral density at lumbar spine and femoral neck (by dual-energy X-ray absorptiometry), and the VFx presence (by X-ray). Results: The cortisol levels after 1 mg DST that were greater than 2.0-g/dl (55 nmol/liter) were the best criteria for detecting patients with both prevalent (73.6% sensitivity, 70.5% specificity) and incident VFx (80% sensitivity, 68.8% specificity) and were associated with a 10-fold increased risk of a new VFx (odds ratio,10.27; 95% confidence interval, 3.39-31.12; P <.0001), regardless of age, gender, bone mineral density at lumbar spine, and prevalent VFx. Conclusions: In AI patients without symptoms of overt hypercortisolism, the cortisol levels after 1 mg DST greater than 2.0-g/dl (55 nmol/liter) represent the best criterion for detecting prevalent and incident VFx. © 2016 by the Endocrine Society.


Chiodini I.,Unit of Endocrinology and Metabolic Diseases | Albani A.,Messina University | Ambrogio A.G.,Neuroendocrinology Research Laboratory | Ambrogio A.G.,University of Milan | And 7 more authors.
Endocrine | Year: 2016

Subclinical Cushing’s syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality. The subclinical Cushing’s syndrome is not rare, being estimated to be between 0.2–2 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing’s syndrome screening, diagnosis and treatment. The Altogether to Beat Cushing’s syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing’s syndrome viewpoint regarding the following controversial issues on Subclinical Cushing’s syndrome (SCS): (1) Who has to be screened for subclinical Cushing’s syndrome? (2) How to screen the populations at risk? (3) How to diagnose subclinical Cushing’s syndrome in patients with an adrenal incidentaloma? (4) Which consequence of subclinical Cushing’s syndrome has to be searched for? (5) How to address the therapy of choice in AI patients with subclinical Cushing’s syndrome? (6) How to follow-up adrenal incidentaloma patients with subclinical Cushing’s syndrome surgically or conservatively treated? Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing’s syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing’s syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing’s syndrome. © 2016 Springer Science+Business Media New York


Bacchi E.,University of Verona | Negri C.,Unit of Endocrinology and Metabolic Diseases | Zanolin M.E.,University of Verona | Milanese C.,University of Verona | And 9 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - To assess differences between the effects of aerobic and resistance training on HbA 1c (primary outcome) and several metabolic risk factors in subjects with type 2 diabetes, and to identify predictors of exercise-induced metabolic improvement. RESEARCH DESIGN AND METHODS - Type 2 diabetic patients (n = 40) were randomly assigned to aerobic training or resistance training. Before and after 4 months of intervention, metabolic phenotypes (including HbA 1c, glucose clamp-measured insulin sensitivity, and oral glucose tolerance test-assessed β-cell function), body composition by dual-energy X-ray absorptiometry, visceral (VAT) and subcutaneous (SAT) adipose tissue by magnetic resonance imaging, cardiorespiratory fitness, and muscular strength were measured. RESULTS - After training, increase in peak oxygen consumption (VO 2peak) was greater in the aerobic group (time-by-group interaction P = 0.045), whereas increase in strength was greater in the resistance group (time-by-group interaction P < 0.0001). HbA 1c was similarly reduced in both groups (-0.40% [95% CI -0.61 to -0.18] vs. -0.35% [-0.59 to -0.10], respectively). Total and truncal fat, VAT, and SAT were also similarly reduced in both groups, whereas insulin sensitivity and lean limb mass were similarly increased. β-Cell function showed no significant changes. In multivariate analyses, improvement in HbA 1c after training was independently predicted by baseline HbA 1c and by changes in VO 2peak and truncal fat. CONCLUSIONS - Resistance training, similarly to aerobic training, improves metabolic features and insulin sensitivity and reduces abdominal fat in type 2 diabetic patients. Changes after training in VO 2peak and truncal fat may be primary determinants of exercise-induced metabolic improvement. © 2012 by the American Diabetes Association.

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