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Vitamin D (VITD) is a key hormone for bone health and has relevant extra-skeletal effects that might play a role in the prevention and treatment of COronaVIrus Disease 19 (COVID-19). Literature regarding this scenario is voluminous but controversial. Glucocorticoid Induced Osteoporosis Skeletal Endocrinology Group (G.I.O.S.E.G) has been present in the scientific debate about the use of VITD and has regularly interfaced national regulatory agencies to ensure appropriateness of its employment. Given the current pandemic and the questions on COVID-19 and VITD, G.I.O.S.E.G. appointed an expert panel to advise how to consider this issue best. The results of these deliberations are reported in the current recommendation paper.

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.

Pituitary tumors are common and require complex and sophisticated procedures for both diagnosis and therapy. To maintain the highest standards of quality, it is proposed to manage patients in pituitary tumors centers of excellence (PTCOEs) with patient-centric organizations, with expert clinical endocrinologists and neurosurgeons forming the core. That core needs to be supported by experts from different disciplines such as neuroradiology, neuropathology, radiation oncology, neuro-ophthalmology, otorhinolaryngology, and trained nursing. To provide high-level medical care to patients with pituitary tumors, PTCOEs further pituitary science through research publication, presentation of results at meetings, and performing clinical trials.

Context A high prevalence of vitamin D (VD) deficiency in COVID-19 patients has been reported and hypothesized to increase COVID-19 severity likely because of its negative impact on immune and inflammatory responses. Furthermore, clear associations between hypovitaminosis D and fat body mass excess and diabetes, factors associated with COVID-19 severity, have been widely recognized. Objective The aim of this study was to evaluate in COVID-19 patients the relationship between VD levels and inflammatory response, body mass index (BMI), blood glucose (GLU), and disease severity. Methods Patients admitted to San Raffaele-Hospital for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing VD metabolism. 25-Hydroxyvitamin D levels, plasma GLU levels, BMI, and inflammatory parameters were evaluated at admission. Results A total of 88 patients were included. Median VD level was 16.3 ng/mL and VD deficiency was found in 68.2% of patients. VD deficiency was found more frequently in male patients and in those affected by severe COVID-19. Regression analyses showed a positive correlation between VD and PaO2/FiO2 ratio, and negative correlations between VD and plasma GLU, BMI, neutrophil/lymphocyte ratio, C-reactive protein, and interleukin 6. Patients with both hypovitaminosis D and diabetes mellitus, as well those with hypovitaminosis D and overweight, were more frequently affected by a severe disease with worse inflammatory response and respiratory parameters, compared to those without or just one of these conditions. Conclusion We showed, for the first-time, a strict association of VD levels with blood GLU and BMI in COVID-19 patients. VD deficiency might be a novel common pathophysiological mechanism involved in the detrimental effect of hyperglycemia and adiposity on disease severity.

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Formenti, Preventing a Covid-19 pandemic Can high prevalence of severe hypovitaminosis D play a role in the high impact of Covid infection in Italy? BMJ. (2020). https://www.bmj.com/content/368/bmj.m810/rr-36 J.P. Bilezikian, D. Bikle, M. Hewison et al. Mechanisms in endocrinology: Vitamin D and COVID-19. Eur J Endocrinol. 20-0665.R1. (2020). https://doi.org/10.1530/EJE-20-0665. Download references Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy Anna Maria Formenti, Erika Pedone, Luigi di Filippo, Fabio Massimo Ulivieri & Andrea Giustina You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Andrea...

Context and Objective COVID-19 has become the most relevant medical issue globally. Despite several studies that have investigated clinical characteristics of COVID-19 patients, no data have been reported on the prevalence of vertebral fractures (VFs). Since VFs may influence cardiorespiratory function and disease outcomes, the aim of this study was to assess VFs prevalence and clinical impact in COVID-19. Design and Patients This was a retrospective cohort study performed at San Raffaele Hospital, a tertiary health care hospital in Italy. We included COVID-19 patients for whom lateral chest x-rays at emergency department were available. VFs were detected using a semiquantitative evaluation of vertebral shape on chest x-rays. Results A total of 114 patients were included in this study and thoracic VFs were detected in 41 patients (36%). Patients with VFs were older and more frequently affected by hypertension and coronary artery disease (P Conclusions VFs may integrate the cardiorespiratory risk of COVID-19 patients, being a useful and easy to measure clinical marker of fragility and poor prognosis. We suggest that morphometric thoracic vertebral evaluation should be performed in all suspected COVID-19 patients undergoing chest x-rays.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.

Medical treatment of prostate cancer (PC) is multidisciplinary, resulting in prolonged survival. Androgen-deprivation therapy (ADT) can have negative effects on skeletal metabolism, particularly if combined with glucocorticoids. We discuss the pathophysiology and effects of ADT and glucocorticoids on skeletal endpoints, as well as the awareness and management of bone fragility. Coadministration of glucocorticoids is necessary with abiraterone because this causes a novel acquired form of 17-hydroxylase deficiency and synergistically increases the risk of fracture by affecting bone quality. Bone antiresorptive agents [selective estrogen receptor modulators (SERMS), bisphosphonates, and denosumab] increase bone mineral density (BMD) and in some instances reduce fracture risk in PC patients on ADT. Awareness and management of bone health in PC can be improved by integrating endocrinologists into the multidisciplinary PC team.

The goal of the clinical management of hypoparathyroidism is to correct acute and chronic hypocalcemia. Treatment of acute hypoparathyroidism via intravenous infusion of Ca++ salts, is necessary only in symptomatic patients, or in asymptomatic patients in the setting of a rapid decrease in ionized Ca

Surgical experience is of paramount importance to reach therapeutic success and minimize operative complications. In the field of pituitary surgery, this led to the concept of Pituitary Center of Excellence (PTCOE) defined as a center where an interdisciplinary team works in collaboration and where surgeons can be trained appropriately to reach and keep excellence in daily practice. To review the literature to define the optimal referral population size to establish a PTCOE to optimize both training and specific field research. A review of the literature was performed about epidemiology. The time needed to observe 200 cases of PAs in a single PTCOE and to reach the minimal surgical experience threshold (MSET) was calculated for different referral population groups. The time needed to reach MSET decreased as population size increased. We defined a population as the optimal one to be served by a single PTCOE with a single dedicated neurosurgeon. PTCOEs should be established after an analysis of the referral population, number of cases suitable for surgical treatment and number of dedicated neurosurgeons.

Background Bone loss and high risk of fractures have been reported in patients with primary hyperthyroidism, whereas data on skeletal health in TSH-secreting adenoma (TSH-oma) are scant, and the risk of fractures in this specific clinical context has not been investigated so far. In this cross-sectional study, we aimed at evaluating for the first time, to our knowledge, the prevalence and determinants of radiological vertebral fractures (VFs) in patients with TSH-oma. Methods Twenty-two patients (10 males, 12 females; median age 47 years) with TSH-oma and 44 patients (20 males, 24 females; median age 49 years) with nonfunctioning pituitary adenoma (NFPA) were retrospectively evaluated for thoracic VFs using a morphometric approach on lateral chest X-ray routinely performed in the presurgical diagnostic workup. Results The prevalence of VFs was significantly higher in TSH-oma vs NFPA (59.1% vs 22.7%; P = 0.003), the difference being still significant (odds ratio, 10.5; P = 0.005) after correction for the size of pituitary adenomas and biochemical parameters. In TSH-oma, the prevalence of VFs was significantly associated with older age (P = 0.007) and higher serum free T4 values (P = 0.02). In 20 patients, data on presurgical medical therapies of TSH-oma were available. All patients not treated with somatostatin receptor ligands were fractured compared with 25% of those who were treated with these drugs (P = 0.001). No significant (P = 0.25) association between VFs and treatment with methimazole was found. Conclusions This study provides the first evidence, to our knowledge, that patients with TSH-oma may develop VFs in close relationship with severity of hyperthyroidism.

Acromegalic osteopathy is an emerging complication of acromegaly, characterized by high bone turnover, profound deterioration in trabecular and cortical bone microstructure, all of which leading to increased risk of vertebral fractures (VFs). The abnormalities of bone quality in acromegaly are not captured by Dual energy X-ray Absorptiometry (DXA) measurement of bone mineral density (BMD), since VFs may occur even in patients with normal or minimally decreased BMD. The purpose of this article is to provide an update on clinical and therapeutic aspects concerning acromegalic osteopathy.

Vitamin D is a target of chronic exposure to glucocorticoid excess, which is the cause of a severe form of secondary osteoporosis. Glucocorticoids affect Vitamin D metabolism at different levels of the enzymatic cascade, thereby decreasing the synthesis of active Vitamin D and impairing its biological action at the tissue level. Moreover, glucocorticoids may directly counteract peripheral effects of Vitamin D, decreasing intestinal calcium absorption and favoring renal calcium loss with consequent negative calcium balance. Therefore, the use of Vitamin D and calcium is mandatory in patients exposed to glucocorticoid excess, although some peculiarities of this treatment should be taken into account to avoid under-treatment of hypovitaminosis D in the specific clinical context of glucocorticoid-induced osteoporosis. This chapter deals with pathophysiological, clinical, and therapeutic aspects of hypovitaminosis D in patients exposed to glucocortoicoid excess.

ObjectiveAccording to the 2015 American Thyroid Association (ATA) guidelines, thyroid ablation by iodine-131 (I-131) therapy is absolutely recommended only in patients with high-risk differentiated thyroid cancer (DTC). Often distant metastases are not recognized early and they can stay silent for long time. The aim of our study was to retrospectively analyze the prevalence of metastatic disease before and after I-131 and to evaluate the influence of the new ATA guidelines in the management of DTC.MethodsWe retrospectively analyzed 140 patients showing distant metastases. All metastases were detected by whole-body scan after I-131 and confirmed by histology and/or other imaging modalities.ResultsIn 26/140 patients metastases were detected before I-131, while in 114/140 were discovered after I-131. Comparing patients with metastases detected before and after I-131, no differences were demonstrated considering age, sex, histotype, tumor size, multifocality of cancer and metastatic localization. Metastatic DTC discovered before radioiodine had higher thyroglobulin and received a higher radioiodine total activity and number of treatments. Considering patients with distant metastases, according to the 2015 ATA guidelines, 38 patients would have been categorized as high risk, 22 as low risk and 80 as intermediate risk. Among intermediate-risk patients, only in 25 cases (31%) I-131 treatment would have been appropriate according to 2015 ATA recommendations; in the remaining 56 cases (69%), I-131 would not have been recommended.ConclusionsAccording to the 2015 ATA guidelines, most of metastatic patients would not have been treated after surgery, with the risk of late diagnosis and delayed treatment.

Introduction: Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant. Subjects and methods: Thirty-eight patients (25 females, 13 males) with acromegaly under Pegvisomant therapy were evaluated for vertebral fractures and bone mineral density at lumbar spine and femoral neck. Gonadal status, serum IGF1 levels and growth hormone receptor genotype were also assessed. Results: Vertebral fractures were detected in 12 patients (31.6%). Fractured patients had longer duration of active disease (p = 0.01) with higher frequency of active acromegaly (p = 0.04), received higher dose of Pegvisomant (p = 0.008), and were more frequently hypogonadic (p = 0.02) as compared to patients who did not fracture. Stratifying the patients for gender, vertebral fractures were significantly associated with Pegvisomant dose (p = 0.02) and untreated hypogonadism (p = 0.02) in males and with activity of disease (p = 0.03), serum insulin-like growth factor-I values (p = 0.01) and d3GHR polymorphism (p = 0.005) in females. No significant association was found between vertebral fractures and bone mineral density at either skeletal site. Conclusion: Vertebral fractures are a frequent complication of long-standing active acromegaly. When patients are treated with Pegvisomant, vertebral fractures may occur in close relationship with active acromegaly and coexistent untreated hypogonadism.

Purpose of Review: This review focuses on the pathophysiological and clinical aspects of diabetes mellitus occurring in patients with Cushing disease (CD). Recent Findings: Insulin resistance and impairment in insulin secretion are both involved in the pathogenesis of glucocorticoid-induced diabetes. Correction of glucocorticoid excess does not always resolve abnormalities of glucose homeostasis, and correction of hyperglycaemia is specifically required. In fact, insulin resistance may persist even after correction of glucocorticoid excess and diabetes needs to be treated for long term. On the other hand, emerging drugs used in the treatment of CD, such as the novel somatostatin analog pasireotide, may have direct effects on glucose homeostasis regardless of control of cortisol excess. Summary: Diabetes mellitus is a frequent and early complication of CD with important diagnostic, prognostic and therapeutic implications. Specifically, diagnosis of CD in patients with diabetes may be difficult due to potential misinterpretation of markers of cortisol hypersecretion. Moreover, diabetes mellitus is often difficult to be controlled in CD requiring a careful and dedicated therapeutic approach. Finally, the coexistence of diabetes may influence the therapeutic decision making in CD, since drugs used in this setting may variably influence glucose homeostasis regardless of control of hypercortisolism.

The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce the endogenous hormonal production and the monitoring of AI treatment may be a challenge for the lack of reliable clinical and biochemical markers. Consequently, several AI patients are frequently exposed to relative glucocorticoid excess potentially leading to develop chronic complications, such as diabetes mellitus, dyslipidemia, hypertension and fragility fractures with consequent impaired QoL and increased mortality risk. This review deals with the pathophysiological and clinical aspects concerning the over-replacement therapy of primary and secondary AI.