Unit of Endocrinology and Metabolic Diseases

Verona, Italy

Unit of Endocrinology and Metabolic Diseases

Verona, Italy
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Morelli V.,Unit of Endocrinology and Metabolic Diseases | Morelli V.,University of Milan | Scillitani A.,Hospital | Arosio M.,University of Milan | Chiodini I.,Unit of Endocrinology and Metabolic Diseases
Journal of Endocrinological Investigation | Year: 2017

Recently, the European Society of Endocrinology (ESE) published new guidelines on the management of adrenal incidentalomas. At the same time Lopez and coworkers published on the Annals of Internal Medicine an important study showing that even patients with non-functioning adrenal tumors have an increased risk of incident diabetes. In consideration of previous data and of the results of the study of Lopez and coworkers, some points emerge from the ESE Guidelines that deserve attention. Firstly, it must be observed that the term “autonomous cortisol secretion,” introduced by the ESE Panel in the place of the commonly used “subclinical hypercortisolism,” seems questionable, since the guidelines do not suggest determining the adrenocorticotroph hormone levels that could give the certain proof of a truly autonomous cortisol secretion. Secondly, the ESE Guidelines suggest against repeated hormonal workup in AI patients with a normal hormonal secretion at initial evaluation, but also in those with a “possible autonomous cortisol secretion,” if in the absence of comorbidities potentially related to hypercortisolism. Thirdly, the ESE Guidelines suggest against further imaging during follow-up in patients with an adrenal mass below 4 cm in size with clear benign features on imaging studies. Considering the available literature data that are briefly summarized in this comment, we believe that no sufficient evidence is available to date for giving sharp-cutting recommendations about the uselessness of a biochemical and morphological follow-up in AI patients, even in those with initially benign and not hypersecreting adrenal adenomas. However, if a recommendation has to be given on the basis of the present evidences, we should suggest to biochemically and morphologically follow-up AI patients for at least 5 years. © 2016, Italian Society of Endocrinology (SIE).


PubMed | Unit of Endocrinology and Metabolic Diseases, Marche Polytechnic University, University of Naples Federico II, Science di Endocrinologia and 2 more.
Type: | Journal: Endocrine | Year: 2016

Subclinical Cushings 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 Cushings 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 Cushings syndrome screening, diagnosis and treatment. The Altogether to Beat Cushings 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 Cushings syndrome viewpoint regarding the following controversial issues on Subclinical Cushings syndrome (SCS): (1) Who has to be screened for subclinical Cushings syndrome? (2) How to screen the populations at risk? (3) How to diagnose subclinical Cushings syndrome in patients with an adrenal incidentaloma? (4) Which consequence of subclinical Cushings syndrome has to be searched for? (5) How to address the therapy of choice in AI patients with subclinical Cushings syndrome? (6) How to follow-up adrenal incidentaloma patients with subclinical Cushings 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 Cushings syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushings syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushings syndrome.


PubMed | Unit of Endocrinology and Metabolic Diseases, Nuclear medicine and Unit of Occupational Medicine
Type: Journal Article | Journal: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA | Year: 2016

The Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients.The Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients.Fifty consecutive Caucasian patients, aged 30-50years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed.Patients showed reduced BMD (Z-scores LS -0.451.00, FN -0.561.01, FT -0.580.92) and TBS (1.2990.111) and increased prevalence of morphometric VFx (32%) than controls (Z-scores LS 0.091.22, FN 0.010.97, FT 0.080.89; TBS 1.3820.176; VFx 8%, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.2450.138 vs 1.3250.086, p<0.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency.EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.


Marzano A.V.,University of Milan | Trevisan V.,University of Milan | Cairoli E.,University of Milan | Eller-Vainicher C.,Unit of Endocrinology and Metabolic Diseases | And 4 more authors.
Orphanet Journal of Rare Diseases | Year: 2015

Background: The presence of hypovitaminosis D in patients with autoimmune bullous skin diseases, such as pemphigus vulgaris (PV) and bullous pemphigoid (BP), is debated. In a previous study we found an increased prevalence of vertebral fractures (VFx) and hypovitaminosis D in PV and BP patients. The present study extends the sample size of the previous one, for investigating the 25-hydroxyvitamin D (25OHVitD) levels in relation with the skeletal health and disease intensity in these patients. Methods: The previous study was performed in 13 PV and 15 BP patients and 28 controls. Data from 39 additional patients (22 PV and 17 BP) were now added. Eventually, we studied 67 patients (35 PV, 32 BP, 51 females), aged 64.7 ± 16.9 years and 67 age-gender- and body mass index-matched controls. In all subjects, serum 25OHVitD, calcium and alkaline phosphatase (ALP) levels were measured, bone mineral density (BMD) was evaluated by Dual-energy X-ray. Absorptiometry at lumbar spine (LS) and femoral neck (FN) and the presence of VFx were ascertained by visual assessment from spinal radiographs. In patients, the disease intensity was evaluated by the autoimmune bullous skin disorder intensity score (ABSIS). Results: As compared with controls, both PV and BP patients showed lower 25OHVitD (22.2 ± 11.1 vs 13.9 ± 8.3 ng/mL, p < 0.001 and 22.4 ± 14.9 vs 9.5 ± 7.7 ng/mL, p < 0.0001, respectively) and higher prevalence of severe hypovitaminosis D (22.9 vs 48.6%, p < 0.02 and 31.1 vs 75.0%, p < 0.0001, respectively) and VFx (28.6 vs 57.1%, p = 0.03 and 34.4 vs 62.5%, P = 0.02, respectively). In both PV and BP patients, LS and FN BMD did not differ from controls. In the whole patients' group, ABSIS score was inversely associated with 25OHVitD levels (R =.0.36, p < 0.005), regardless of age (â =.3.2, P = 0.009). Conclusions: PV and BP patients have an increased prevalence of hypovitaminosis D and VFx. The extended study shows, for the first time, that the 25OHVitD levels are inversely associated with disease intensity and that VFx occur in spite of a not reduced BMD. © 2015 Marzano et al.; licensee Biomed Central.


Cairoli E.,Unit of endocrinology and Metabolic Diseases | Cairoli E.,University of Milan | Eller-Vainicher C.,Unit of endocrinology and Metabolic Diseases | Chiodini I.,Unit of endocrinology and Metabolic Diseases | Chiodini I.,University of Milan
International Journal of Women's Health | Year: 2015

Patient adherence to many osteoporosis treatments, primarily bisphosphonates, is generally poor, thus leading to a significant reduction in antifracture efficacy. Patient perceptions about the necessity of the prescribed medication to treat osteoporosis and the concerns about the potential adverse effects are important and potentially modifiable determinants of adherence, in addition to other factors, such as difficult dosing regimens and high dosing frequency. Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL), which, through the prevention of the RANKL/RANK interaction, inhibits osteoclast-mediated bone resorption and significantly reduces the risk of vertebral, nonvertebral, and hip fractures. It is administered subcutaneously every 6 months for the treatment of postmenopausal osteoporosis. Preference and adherence to Dmab treatment were assessed in various clinical trials. Although with some limitations, available data suggest that Dmab is preferred to bisphosphonates, produces greater satisfaction than bisphosphonates, and would be preferentially chosen for long-term treatment. Moreover, patient perceptions about the necessity of Dmab treatment clearly outweigh the concerns about the injections, and positive beliefs about treatment positively influence medication-taking behavior. According to these data, Dmab may represent a reasonable alternative to bisphosphonates, particularly for osteoporotic women in whom a suboptimal or even poor adherence to oral treatments is expected. © 2015 Cairoli et al.


Cairoli E.,Unit of Endocrinology and Metabolic Diseases | Cairoli E.,University of Milan | Zhukouskaya V.V.,Unit of Endocrinology and Metabolic Diseases | Zhukouskaya V.V.,University of Milan | And 4 more authors.
Journal of Endocrinological Investigation | Year: 2015

Osteoporosis is a skeletal disease which predisposes to fragility fractures with high morbidity and economic impact, and, therefore, the goal of any osteoporosis treatment is to reduce the fracture risk. In the various forms of osteoporosis an imbalance between bone resorption and apposition is present, that generally leads to a reduction of bone mineral density and bone quality, and finally to the increased fracture risk. Nowadays, several drugs are available with a demonstrated anti-fracturative effect obtained by inhibiting bone resorption or stimulating bone formation. However, their use is not free from limitations and side effects. Importantly, to date, the available antiresorptive drugs have also an inhibiting, though to a lesser extent, effect on bone apposition and, similarly, the anabolic drugs lead to an increase also of bone resorption. Advances in our knowledge about bone biology, with molecular insights into mechanisms underlying osteoblast, osteoclast, and osteocyte activity, have led to the recognition of new potential targets and consequently to the formulation of new therapeutic agents to treat osteoporosis. New potential developments among the antiresorptive drugs include cathepsin K inhibitors and among the osteoanabolic drugs those activating the Wnt signaling pathway, such as the monoclonal antibodies against sclerostin. The novelty of these compounds is that their mechanism of action gives the exciting possibility to uncouple bone resorption and bone formation, and data available so far appear to be promising. Finally, several new therapeutic targets are under investigation in preclinical studies which could open further approaches to treat osteoporosis in the future. © 2015 Italian Society of Endocrinology (SIE).


PubMed | Unit of Endocrinology and Metabolic Diseases and University of Milan
Type: | Journal: International journal of women's health | Year: 2015

Patient adherence to many osteoporosis treatments, primarily bisphosphonates, is generally poor, thus leading to a significant reduction in antifracture efficacy. Patient perceptions about the necessity of the prescribed medication to treat osteoporosis and the concerns about the potential adverse effects are important and potentially modifiable determinants of adherence, in addition to other factors, such as difficult dosing regimens and high dosing frequency. Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-B ligand (RANKL), which, through the prevention of the RANKL/RANK interaction, inhibits osteoclast-mediated bone resorption and significantly reduces the risk of vertebral, nonvertebral, and hip fractures. It is administered subcutaneously every 6 months for the treatment of postmenopausal osteoporosis. Preference and adherence to Dmab treatment were assessed in various clinical trials. Although with some limitations, available data suggest that Dmab is preferred to bisphosphonates, produces greater satisfaction than bisphosphonates, and would be preferentially chosen for long-term treatment. Moreover, patient perceptions about the necessity of Dmab treatment clearly outweigh the concerns about the injections, and positive beliefs about treatment positively influence medication-taking behavior. According to these data, Dmab may represent a reasonable alternative to bisphosphonates, particularly for osteoporotic women in whom a suboptimal or even poor adherence to oral treatments is expected.


PubMed | Unit of Endocrinology and Metabolic Diseases and University of Milan
Type: | Journal: Orphanet journal of rare diseases | Year: 2015

The presence of hypovitaminosis D in patients with autoimmune bullous skin diseases, such as pemphigus vulgaris (PV) and bullous pemphigoid (BP), is debated. In a previous study we found an increased prevalence of vertebral fractures (VFx) and hypovitaminosis D in PV and BP patients. The present study extends the sample size of the previous one, for investigating the 25-hydroxyvitamin D (25OHVitD) levels in relation with the skeletal health and disease intensity in these patients.The previous study was performed in 13 PV and 15 BP patients and 28 controls. Data from 39 additional patients (22 PV and 17 BP) were now added. Eventually, we studied 67 patients (35 PV, 32 BP, 51 females), aged 64.716.9 years and 67 age- gender- and body mass index-matched controls. In all subjects, serum 25OHVitD, calcium and alkaline phosphatase (ALP) levels were measured, bone mineral density (BMD) was evaluated by Dual-energy X-ray. Absorptiometry at lumbar spine (LS) and femoral neck (FN) and the presence of VFx were ascertained by visual assessment from spinal radiographs. In patients, the disease intensity was evaluated by the autoimmune bullous skin disorder intensity score (ABSIS).As compared with controls, both PV and BP patients showed lower 25OHVitD (22.211.1 vs 13.98.3 ng/mL, p<0.001 and 22.414.9 vs 9.57.7 ng/mL, p<0.0001, respectively) and higher prevalence of severe hypovitaminosis D (22.9 vs 48.6%, p<0.02 and 31.1 vs 75.0%, p<0.0001, respectively) and VFx (28.6 vs 57.1%, p=0.03 and 34.4 vs 62.5%, P=0.02, respectively). In both PV and BP patients, LS and FN BMD did not differ from controls. In the whole patients group, ABSIS score was inversely associated with 25OHVitD levels (R=-0.36, p<0.005), regardless of age (=-3.2, P=0.009).PV and BP patients have an increased prevalence of hypovitaminosis D and VFx. The extended study shows, for the first time, that the 25OHVitD levels are inversely associated with disease intensity and that VFx occur in spite of a not reduced BMD.


PubMed | Unit of Endocrinology and Metabolic Diseases and University of Milan
Type: | Journal: Journal of endocrinological investigation | Year: 2016

Recently, the European Society of Endocrinology (ESE) published new guidelines on the management of adrenal incidentalomas. At the same time Lopez and coworkers published on the Annals of Internal Medicine an important study showing that even patients with non-functioning adrenal tumors have an increased risk of incident diabetes. In consideration of previous data and of the results of the study of Lopez and coworkers, some points emerge from the ESE Guidelines that deserve attention. Firstly, it must be observed that the term autonomous cortisol secretion, introduced by the ESE Panel in the place of the commonly used subclinical hypercortisolism, seems questionable, since the guidelines do not suggest determining the adrenocorticotroph hormone levels that could give the certain proof of a truly autonomous cortisol secretion. Secondly, the ESE Guidelines suggest against repeated hormonal workup in AI patients with a normal hormonal secretion at initial evaluation, but also in those with a possible autonomous cortisol secretion, if in the absence of comorbidities potentially related to hypercortisolism. Thirdly, the ESE Guidelines suggest against further imaging during follow-up in patients with an adrenal mass below 4cm in size with clear benign features on imaging studies. Considering the available literature data that are briefly summarized in this comment, we believe that no sufficient evidence is available to date for giving sharp-cutting recommendations about the uselessness of a biochemical and morphological follow-up in AI patients, even in those with initially benign and not hypersecreting adrenal adenomas. However, if a recommendation has to be given on the basis of the present evidences, we should suggest to biochemically and morphologically follow-up AI patients for at least 5years.


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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