Publications by authors named "I Chiodini"

155 Publications

When to suspect hidden hypercortisolism in type 2 diabetes: a meta-analysis.

Endocr Pract 2021 Jul 26. Epub 2021 Jul 26.

Department of Endocrine and Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, Milan, Italy; Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. Electronic address:

Objective: Among patients with type 2 diabetes (T2D), the prevalence of hidden hypercortisolism (HidHyCo, formally called subclinical hypercortisolism or mild autonomous cortisol secretion) was estimated to be 2.2-12.1%. The aim of this study was to investigate whether the available literature helps to identify the characteristics of T2D patients more frequently associated with HidHyCo.

Methods: A meta-analysis was performed using studies that assessed both the prevalence of HidHyCo in patients with T2D and the characteristics of these patients with and without HidHyCo. The DerSimonian and Laird (DSL) and the Hartung, Knapp, Sidik and Jonkman (HKSJ) methods were utilized.

Results: Among the 18 available studies, 6 studies provided the necessary data. The association between HidHyCo and advanced T2D (based on the patients' description given in each study in presence of micro/ microvascular complications, or insulin treatment plus hypertension, or hypertension treated with ≥2 drugs), hypertension, insulin treatment and dyslipidemia was reported in 5 (2184 patients), 6 (2283 patients), 3 (1440 patients), and 3 (987 patients) studies, respectively. HidHyCo was associated with advanced T2D as assessed with both DSL (odds ratio, OR, 3.47, 95% Confidence Interval, 95%CI, 2.12-5.67) and HKSJ method (OR 3.60, 95%CI 2.03-6.41) and with the prevalence of hypertension or of insulin treatment as assessed by the DSL approach (OR 1.92, 95%CI 1.05-3.50 and OR 2.29, 95%CI 1.07-4.91, respectively), but not as assessed with HKSJ method.

Conclusions: Patients with advanced T2D have a higher prevalence of HidHyCo. These data inform about the selection of T2D patients for HidHyCo screening.
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http://dx.doi.org/10.1016/j.eprac.2021.07.014DOI Listing
July 2021

Bisphosphonates after Denosumab withdrawal reduce the vertebral fractures incidence.

Eur J Endocrinol 2021 Jul 1. Epub 2021 Jul 1.

C Eller-Vainicher, Endocrinology and Diabetology Units, Department of Medical Sciences and Community, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Objective: Several studies showed the occurrence of vertebral fracture (VFx) in patients discontinuing denosumab (Dmab), suggesting the need of bisphosphonate (BPs) therapy to mitigate this VFx risk increase. However, the morphometric VFx (morphoVFx) incidence after Dmab discontinuation and the BPs effect on VFx risk in this setting are still a matter of debate.

Design: Retrospective, monocentric study.

Methods: In 120 patients (111 females) discontinuing Dmab, 19 have not been treated (Not-treated Group, 16 females, age 63.5±15.0 years) and 101 patients have been treated (Treated Group, 95 females, age 70.0±10.6 years) with BPs (28 alendronate, ALN; 73 zoledronate, ZOL, single infusion), respectively. We evaluated the incidence of both clinical VFx and morphoVFx in Treated Group and Non-treated Group.

Results: Patients in Treated Group showed a 5.5% VFx incidence (n=6, 3 clinical, 3 morpho VFx), which was anyway lower than Not-treated Group patients (n=4, 21.1%, 4 clinical, 3 multiple, p=0.029), despite a comparable FRAX score at the time of Dmab initiation. The logistic regression analysis showed that the VFx incidence was independently associated with the lack of BPs treatment (odds ratio 13.9, 95% confidence interval 1.7-111.1, p=0.014), but not with the number of Dmab injections, age, duration of BPs before Dmab initiation, the BMD at Dmab withdrawal and the prevalence of VFx at Dmab withdrawal.

Conclusions: The Dmab withdrawal is associated with an increased risk of clinical but not morphometric VFx. Therapy with ALN or with a single ZOL treatment are partially effective in reducing the increased VFx risk after Dmab withdrawal.
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http://dx.doi.org/10.1530/EJE-21-0157DOI Listing
July 2021

Spine Bone Texture Assessed by Trabecular Bone Score in Active and Controlled Acromegaly: A Prospective Study.

J Endocr Soc 2021 Aug 15;5(8):bvab090. Epub 2021 May 15.

Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Context: Acromegalic patients have an increased vertebral fracture (VFx) risk due to bone quality reduction, independently of bone mineral density (BMD).

Objective: The aim of the study is to describe bone quality in acromegaly, measured by trabecular bone score (TBS), a noninvasive index for assessing bone microarchitecture.

Methods: We collected data from 18 patients (13 female, age 56.2 ± 15 years) newly diagnosed with acromegaly. Thirty-six age- and sex-matched healthy controls were also recruited. Pituitary function, bone and calcium-phosphorous metabolism, and BMD at spine and femur and TBS (by dual-energy x-ray absorptiometry) were assessed in acromegalic patients at diagnosis and 12 months after the achievement of insulin-like growth factor 1 (IGF-1) normalization.

Results: At diagnosis, BMD and the VFx prevalence were comparable between patients and controls (28.3 ± 5.9 vs 27.6 ± 3.7 and 11% vs 8.3%), whereas TBS was significantly lower in acromegalic patients (1.20 ± 0.13 vs 1.30 ± 0.06;  < .001) and carboxyterminal telopeptide (CTX) and osteocalcin were significantly higher compared to controls (707 ± 365.7 vs 371 ± 104.1 pg/mL;  = .001 and 31.6 ± 15.4 vs 17.0 ± 5.7 ng/mL;  = .001, respectively). One year after IGF-1 normalization, a significant reduction of bone turnover indexes was observed in the group of acromegalic patients surgically cured (osteocalcin decrease of 61.2%, CTX decrease of 60.3%) compared to the ones controlled by medical therapy (osteocalcin decrease of 39%, CTX decrease of 40.7%;  = .01 and  = .001, respectively). Despite these findings, no TBS or BMD variations were observed.

Conclusion: Acromegalic patients have impaired bone quality despite normal density. Achieving normal growth hormone secretion rapidly leads to the normalization of bone turnover.
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http://dx.doi.org/10.1210/jendso/bvab090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237850PMC
August 2021

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy.

BMC Infect Dis 2021 Jun 14;21(1):566. Epub 2021 Jun 14.

Department of Endocrine and Metabolic Diseases & Lab of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, Via Magnasco 2, 20149, Milan, Italy.

Background: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19.

Methods: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization.

Results: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ - 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count.

Conclusion: In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.
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http://dx.doi.org/10.1186/s12879-021-06281-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200788PMC
June 2021

Management of bone fragility in type 2 diabetes: Perspective from an interdisciplinary expert panel.

Nutr Metab Cardiovasc Dis 2021 Jul 28;31(8):2210-2233. Epub 2021 Apr 28.

Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, Siena, Italy. Electronic address:

Aim: Bone fragility is increasingly recognized as a relevant complication of type 2 diabetes (T2D) and diabetic patients with fragility fractures have higher mortality rates than non diabetic individuals or diabetic patients without fractures. However, current diagnostic approaches for fracture risk stratification, such as bone mineral density measurement or the use of risk assessment algorithms, largely underestimate fracture risk in T2D patients. A multidisciplinary expert panel was established in order to in order to formulate clinical consensus recommendations on bone health assessment and management of fracture risk in patients with T2D.

Data Synthesis: The following key questions were addressed: a) which are the risk factors for bone fragility in T2D?, b) which diagnostic procedures can be currently used to stratify fracture risk in T2D patients?, c) which are the effects of antidiabetic treatments on bone?, and d) how to prevent and treat bone fragility in T2D patients? Based on the available data members of this panel suggest that the stratification of fracture risk in patients with diabetes should firstly rely on the presence of a previous fragility fracture and on the individual risk profile, with the inclusion of T2D-specific risk factors (namely T2D duration above 10 yrs, presence of chronic T2D complications, use of insulin or thiazolidinediones and persistent HbA1c levels above 8% for at least 1 year). Two independent diagnostic approaches were then suggested in the presence or the absence of a prevalent fragility fracture, respectively.

Conclusions: Clinical trials in T2D patients at risk for fragility fractures are needed to determine the efficacy and safety of available antiresorptive and anabolic agents in this specific setting.
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http://dx.doi.org/10.1016/j.numecd.2021.04.014DOI Listing
July 2021
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