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BackgroundDespite COVID-19 being identified as severe respiratory viral infection, progressively many relevant endocrine manifestations have been reported greatly contributing to the severity of the clinical presentation. Systemic involvement in COVID-19 is due to the ubiquitous expression of angiotensin-converting enzyme 2 (ACE2) receptor, responsible for the entry in the cells of SARS-CoV-2, Several reports in humans and animal models showed a significant ACE2 mRNA expression in hypothalamus and pituitary cells. Moreover, higher mortality and poorer outcomes have been widely described in COVID-19 patients with obesity, diabetes and vertebral fractures, which are all highly prevalent in subjects with pituitary dysfunctions.AimTo review the main endocrine manifestations of COVID-19 with their possible implications for pituitary diseases, the possible direct and indirect involvement of the pituitary gland in COVID-19, the impact of COVID-19 on the management of established pituitary diseases which can be already at increased risk for worse outcomes and on neurosurgical activities as well as vaccination.ConclusionsOur review underlines that there could be a specific involvement of the pituitary gland which fits into a progressively shaping endocrine phenotype of COVID-19. Moreover, the care for pituitary diseases need to continue despite the restrictions due to the emergency. Several pituitary diseases, such as hypopituitarism and Cushing disease, or due to frequent comorbidities such as diabetes may be a risk factor for severe COVID-19 in affected patients.There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in the pandemic in order to issue evidence driven recommendations for the management of pituitary patients in the persistent COVID-19 emergency.

Besides the pulmonary manifestations caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), an emerging endocrine phenotype, which can heavily impact on the severity of the syndrome, has been recently associated with coronavirus disease 2019 (COVID-19). Patients with pituitary diseases or the pituitary gland itself may also be involved in COVID-19 clinical presentation and/or severity, causing pituitary apoplexy.Moreover, hypopituitarism is frequently burdened by several metabolic complications, including arterial hypertension, hyperglycemia, obesity and vertebral fractures, which have all been associated with poor outcomes and increased mortality in patients infected by SARS-CoV-2.This review will discuss hypopituitarism as a condition that might have a bidirectional relationship with COVID-19 due to the frequent presence of metabolic comorbidities, to the direct or indirect pituitary damage or being per se a potential risk factor for COVID-19. Finally, we will address the current recommendations for the clinical management of vaccines in patients with hypopituitarism and adrenal insufficiency.

Diabetic patients are at higher risk of developing infectious diseases and severe complications, compared to the general population. Almost no data is available in the literature on influenza immunization in people with type 1 diabetes mellitus (T1DM). As part of a broader project on immunization in diabetic patients, we conducted a cross-sectional study to: (i) report on seasonal influenza coverage rates in T1DM patients, (ii) explore knowledge, attitudes, and practices (KAPs) towards seasonal influenza in this population, and (iii) identify factors associated with vaccine uptake, including the role of family doctors and diabetologists. A survey was administered to 251 T1DM patients attending the Diabetes Clinic at San Raffaele Research Hospital in Milan, Italy and individual-level coverage data were retrieved from immunization registries. Self-reported seasonal influenza immunization coverage was 36%, which decreased to 21.7% when considering regional immunization registries, far below coverage target of 75%. More than a third (36.2%) of T1DM patients were classified as pro-vaccine, 30.7% as hesitant, 17.9% as uninformed, and 15.1% as anti-vaccine. Diabetologists resulted to be the most trusted source of information on vaccines’ benefits and risks (85.3%) and should be more actively involved in preventive interventions. Our study highlights the importance of developing tailored vaccination campaigns for people with diabetes, including hospital-based programs involving diabetes specialists.

Abstract Context Skeletal fragility is observed in 30% to 60% of acromegaly patients, representing an emerging complication of the disease that increases disability. Despite several studies having investigated the clinical and hormonal prognostic factors for the occurrence of vertebral fractures (VFs) in acromegaly, very few data are available on their prevention/treatment including the effect of vitamin D (VD) supplementation, which has been reported to have a fracture-protective effect in several studies in patients with osteoporosis. Objective We aimed to investigate the role of cholecalciferol (D3) supplementation in the prevention of incident VFs (i-VFs) in acromegaly. Methods A longitudinal, retrospective and multicenter study was performed on 61 acromegaly patients treated and untreated with D3 supplementation. Results Twenty-six patients were treated with D3 supplementation according to clinical guidelines. The median D3 weekly dosage was 8500 IU (interquartile range [IQR]: 3900). The median duration of D3 supplementation was 94 months (IQR: 38). At last follow-up, i-VFs were diagnosed in 14 patients (23%). I-VFs were less prevalent in patients on D3 supplementation (14.3% of cases) compared to patients not treated with D3 (85.7%; P = .02). The final level of serum V25OH-D was significantly lower in patients who developed i-VFs (28.6 ng/mL, IQR: 4.1) compared to patients who did not develop i-VFs (34.2 ng/mL, IQR: 9.6; P = .05). The logistic regression confirmed the protective role of D3 supplementation on the occurrence of i-VFs (odds ratio: 0.16; 95% CI, 0.03-0.79; P = .01). Conclusion It is likely that D3 supplementation could lead to a reduction in i-VFs in acromegaly.

Abstract Context Several case reports of Graves’ disease (GD) occurrence after COVID-19 vaccination that are possibly related to the autoimmune syndrome induced by adjuvants (ASIA) were published recently. Objective The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021. Methods Patients with a first episode of GD attending a tertiary endocrine center between January 1, 2021, and December 31, 2021, were included. Results Sixty-four patients with a first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared with the other 44 patients, the 20 patients with postvaccine early-onset (PoVEO) GD were older (median age 51 years vs 35 years, P = .003) and more likely to be male (40.0% vs 13.6%, P = .018). At diagnosis, the biochemical and immune profiles were similar between the 2 groups. However, at 3 months after starting methimazole, patients with PoVEO GD had significantly lower thyrotropin receptor antibody titer and were taking lower doses of methimazole than the other patients with GD. None in the PoVEO group had sustained free triiodothyronine elevation. Conclusion This relatively large series suggests that in 2021 PoVEO GD may be a new nosologic entity representing one-third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence, and a better initial biochemical and immunologic response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurring GD.

This paper is one of the outcomes of the 5th International Conference \"Controversies in Vitamin D\" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.

Low Vitamin D (VD) levels in COVID-19 patients have been related to increased disease severity and worse outcomes. However, most of these trials designs were not-controlled and retrospective, including patients with demographic differences and biases potentially influencing the reported associations between lower VD levels and severe COVID-19. Aim of this study was to prospectively evaluate VD levels influence on disease severity in a COVID-19 patients cohort matched for age, sex and comorbidities with control subjects. Patients admitted to San Raffaele University Hospital for COVID-19 from March to June 2021 were consecutively enrolled in this study, which was approved by the local IRB, after giving their informed consent. Severe (i. e. those needing high flow oxygen therapy) and non-severe COVID-19 patients matched for age, sex and comorbidities were recruited at admission in Emergency Department (ED). Control subjects from the outpatient Endocrinology Unit of the same Hospital were enrolled in the same period. We excluded patients with comorbidities and therapies influencing VD metabolism. 25OH-VD levels were evaluated at admission in ED and VD deficiency was defined by serum 25OH-VD below 20 ng/mL. A total of 73 COVID-19 patients and 30 control subjects were included in the study. No differences regarding age, sex and comorbidities were found between patients and control groups, but 25OH-VD levels were statistically lower in COVID-19 patients (13.3 vs 23.6 ng/mL, p<0. 001) with a higher prevalence of VD deficiency (75% vs 43%, p=0. 002). After the ED admission, during the hospitalization, a severe disease occurred in a total of 46 COVID-19 patients, and 27 were affected by a non-severe one. No differences regarding age, sex and comorbidities were found between severe vs non-severe groups, but 25OH-VD was significantly lower in the severe one (11.7 vs 16.7 ng/mL, p=0. 007) with a higher prevalence of VD deficiency (85% vs 59%, p=0. 015). We observed lower 25OH-VD levels at admission in patients with non-invasive mechanical ventilation requirement (n.18) and in those admitted in intensive care unit (n.8) during hospitalization, compared to the other patients (p=0. 003 and p=0. 01), although no differences regarding age and comorbidities were found. Moreover, in patients with VD deficiency we found higher levels of inflammatory markers C-reactive protein and ferritin (69 vs 42 mg/L, p=0. 036; 723 vs 414 ng/mL, p=0. 028), and lower SaO2/FiO2 and PaO2/FiO2 ratios (433 vs 447, p=0. 005; 261 vs 311; p<0. 001) at hospital admission. In conclusion, our prospective data confirm that low VD levels are widely found in hospitalized COVID-19 patients compared to control subjects and predict increased disease severity independently from age, sex and comorbidities of patients affected. We suggest that tackling VD deficiency may be an effective preventive measure to prevent severe COVID-19. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

High prevalence of vitamin D (VD) deficiency in COVID-19 patients was reported by several studies. Since VD is a key regulating factor of both innate and adaptive immunity, it was hypothesized that VD deficiency may predispose to SARS-CoV-2 infection and lower levels of VD could be related to increased COVID-19 severity and worse outcome risks. However, to date, only few studies partially investigated the relationship between VD and inflammatory and immune response and clinical features of COVID-19 patients. The aim of this study is to evaluate the influence of vitamin D levels on COVID-19 inflammatory activity, clinical pattern and disease severity. Patients admitted to San Raffaele University Hospital for COVID-19 from February 2020 were enrolled in this study. We excluded patients with comorbidities and therapies influencing VD metabolism. 25OH-Vitamin D levels were evaluated at admission in hospital and VD insufficiency and deficiency were defined as VD level below 30 ng/mL and 20 ng/mL, respectively. A total of 88 patients were included in the study. Median (IQR) VD levels were 16.3 (11.2–23.9) ng/mL. VD insufficiency and deficiency were found in 88.6% and in 68.2% of patients, respectively. Linear regression analyses showed a positive correlation between VD levels and PaO2/FiO2 ratio (p=0.019; r=0.254), and negative correlations between VD levels and Neutrophil/Lymphocyte (N/L) ratio (p=0.04; r=-0.19), C-reactive protein (CRP) levels (p=0.047; r=-0.18) and Interleukin 6 (IL-6) levels (p=0.04; r=-0.22). Lower VD levels were found in patients affected by severe disease (needs for high-flow oxygen therapy and/or noninvasive mechanical ventilation, admitted to ICU and/or dead) than non-severe patients (13.4 ng/mL [10.37–19.15] vs 18.45 ng/mL [15.15–24.95]; p=0.007). Moreover, patients with VD deficiency had higher levels of CRP, LDH, IL-6, IFN-gamma (p=0.04, p=0.01, p=0.002, p=0.04; respectively), lower PaO2/FiO2 and higher N/L ratios (p=0.008, p=0.004; respectively), and higher rate of severe disease (65% vs 39%, p=0.02), as compared to VD non-deficient ones. In conclusion, low VD levels are widely found in hospitalized COVID-19 and may lead to increased disease severity through an excessive immune-inflammatory response. Our data suggest that reaching adequate vitamin D levels in risky population may contribute to prevention of COVID-19 occurrence and severity.

Background: Persistent hypoparathyroidism (PH) is a rare disease due to an impaired secretion of PTH, mostly occurring as a complication of total thyroidectomy. Calcium and calcitriol are currently the most common and inexpensive therapies, although not all the patients easily achieve control of the disease. Recently, our group has reported that BMI at diagnosis can predict calcitriol resistance in PH. Very few studies have been performed with fractures as primary endpoint in hypoparathyroidism, and we still not know if PH could be predisposing to an increased risk of morphometric fractures and possible clinical and biochemical predicting factors. Patients and methods: To that end we retrospectively evaluated the anthropometric, biochemical and fracture characteristics in 71 consecutive patients with PH (F/M= 62/9; median age 58.7 yrs, range: 29-87; 67 with post-surgical PH and 4 with autoimmune PH). All patients were hypoparathyroid from at least one year (median duration of disease: 9 yrs., range: 1-41) and were under standard treatment with calcium and active vitamin D analogs (calcitriol). For each patient anthropometric data (BMI=kg/m2; N= Normal weight patients <25; OO= Obese and overweight patients with BMI > 25) were collected, as well as biochemical parameters, such as calcium (mg/dl) and 25 OH vitamin D (25OHD expressed as ng/ml). We considered well controlled (C) patients with calcium between 8.2 and 9.2 mg/dl and not controlled (NC) under 8.2 or above 9.2 mg/dl. Vertebral fractures (VF) were assessed by a quantitative morphometric approach by using images provided by DXA and classified according to Genant classification. Results: Thirteen out of 71 patients (18%) were fractured. We showed a positive linear correlation in the overall population between BMI and calcitriol intake (p=0.006, CI 95% [1.2-6.9]) while no significant difference in prevalence of VF in OO vs N group (8/40 vs 5/31, p=0.76) was found. However, almost half (6/13, 45%) of patients with VF were OO NC. Moreover, 86% of NC vs only 30% of C fractured patients (6/7 vs 2/6) were OO Discussion: We report a high prevalence of VF in hypoparathyroidism. Moreover, we confirm that increased BMI is associated with higher needs of calcitriol to obtain calcium control. Interestingly, our data suggest for the first time that OO hypoparathyroid patients with NC disease are those at highest risk of fracture. Therefore, in this subset of patients a more intensive and proactive biochemical and bone monitoring should be adviced if these results will be confirmed in larger studies.