Prevalence and patterns of anti-osteoporotic drug use based on 2019 real-world nationwide data in Greece.

We used the Greek nationwide database to capture individuals on anti-osteoporotic treatment during 2019. From the estimated number of 683,679 osteoporotic individuals, only 42% were receiving treatment, with the total annual cost being almost one-tenth of the total cost of fractures. The treatment gap was significantly higher in males than in females. INTRODUCTION: Based on the 2019 European scorecard (SCOPE), osteoporosis is diagnosed in an estimated 683,679 individuals in Greece, with the direct cost of incident fractures being €694.7 million, although further relevant real-world data are scarce. METHODS: The e-Government Center for Social Security Services prescription database, which covers almost 100% of the Greek population, was used to capture all individuals on anti-osteoporotic treatment during 2019. RESULTS: A total of 288,983 among 8,641,341 people, corresponding to 3.3% of the total adult Greek population, had filled at least one anti-osteoporotic prescription (6.0% and 0.36% for females and males, respectively). Prevalence of anti-osteoporotic treatment increased with age, from 0.15% in those younger than 50 to 8.6% in those older than 70 years. Oral bisphosphonates were more frequently prescribed (58.8%), followed by denosumab (39.4%). Alendronate was more frequently prescribed in males and in people younger than 60 years. Denosumab was more frequently prescribed in females and in people older than 60 years. Selective estrogen-receptor modulators, teriparatide, and parenteral bisphosphonates accounted for 1.1%, 1.0%, and 0.02% of all prescriptions, respectively. Orthopedic surgeons (39.6%), endocrinologists (19.6%), general practitioners (19%), and rheumatologists (9.3%) prescribed the vast majority of anti-osteoporotic regimens, with significant differences in prescription patterns. The annual cost of treatment per patient increased significantly with age, being on average €323.33. CONCLUSIONS: Less than half of the estimated number of individuals with osteoporosis in 2019 in Greece received treatment, with the total annual cost being far less than the estimated cost of incident-fragility fractures. The impact of this undertreatment on related health care costs merits further investigation.

MANAGEMENT OF ENDOCRINE DISEASE: Dysnatraemia in COVID-19: prevalence, prognostic impact, pathophysiology, and management.

This review examines the prevalence, aetiology, pathophysiology, prognostic value, and investigation of dysnatraemia in hospitalised COVID-19 patients, taking into account all relevant studies published in PubMed and Cochrane Library studies until March 2021. Hyponatraemia is commonly observed in patients with bacterial pneumonia and is an independent predictor for excess mortality and morbidity. However, it remains unknown whether this association applies to coronavirus disease-2019 (COVID-19). Several studies reported a 20-35% prevalence for hyponatraemia and 2-5% for hypernatraemia in patients admitted with COVID-19. In addition, hyponatraemia on admission was a risk factor for progression to severe disease, being associated with an increased likelihood for the need for invasive mechanical ventilation, with an odds ratio (OR) of 1.83-3.30. Hyponatraemia seems to be an independent risk factor for mortality, with an OR of 1.40-1.50 compared to normonatraemia, while hypernatraemia is related to even worse outcomes than hyponatraemia. Furthermore, preliminary data show an inverse association between serum sodium and interleukin-6 levels, suggesting that hyponatraemia might be used as a surrogate marker for the risk of a cytokine storm and the need for treatment with interleukin antagonists. In conclusion, dysnatraemia is common and carries a poor prognosis in COVID-19 patients, indicating that it may play a future role in risk stratification and individualising therapy.

Impact of the COVID-19 pandemic on neuroendocrine tumour services in England.

PURPOSE: During the COVID-19 pandemic, there have been particular concerns regarding the related impact on specialist tumour services. Neuroendocrine tumour (NET) services are delivered in a highly specialised setting, typically delivered in a small number of centres that fulfil specific criteria as defined by the European Neuroendocrine Tumour Society (ENETS). We aimed to address the COVID-19-related impact on specialist NET tumour services in England and other countries. METHODS: Electronic survey addressing patient access and delivery of care distributed to all ENETS Centres of Excellence (CoE) in England and matching number of ENETS CoE elsewhere. Semi-quantitative and qualitative analyses of survey responses were performed. RESULTS: Survey response of ENETS CoE in England was 55% (6/11). Responses from six non-UK ENETS CoE elsewhere were received and analysed in a similar manner. Relevant disruption of various NET services was noted across all responding Centres, which included delayed patient appointments and investigations, reduced availability of treatment modalities including delayed surgical treatment and a major negative impact on research activities. The comparison between English and non-UK ENETS CoE suggested that the former had significantly greater concerns related to future research funding (p = 0.014), whilst having less disruption to multidisciplinary meetings (p = 0.01). A trend was also noted towards virtual patient appointments in ENETS CoE in England vs. elsewhere (p = 0.092). CONCLUSIONS: Restoration of highly specialised NET services following COVID-19 and planning for future service delivery and research funding must take account of the severe challenges encountered during the pandemic.

Magnetic Resonance Imaging or Endoscopic Ultrasonography for Detection and Surveillance of Pancreatic Neuroendocrine Neoplasms in Patients with Multiple Endocrine Neoplasia Type 1?

Our aim was to compare the clinical utility of Magnetic Resonance Imaging (MRI) and Endoscopic Ultrasonography (EUS) in identifying Pancreatic Neurondocrine Neoplasms (PanNENs) and monitoring size alterations in Multiple Endocrine Neoplasia type 1 (MEN1) patients. Thirty-one MEN1 patients with PanNENs and concurrent screening by EUS and abdominal MRI were included and 129 pancreatic lesions were detected in total. MRI detected fewer lesions than EUS (n=73 vs. 110, p=0.006). MRI sensitivity and specificity compared to EUS at 20 and 10 mm cut-offs of maximal lesion diameter were 96 and 88% (20 mm cut-off) and 90 and 82%(10 mm cut-off), respectively (concordance rates of 97 and 87% and Cohen's kappa=0.912 and 0.718, respectively). Lesions<1 cm were more often detected with EUS (p=0.025). Data from sequential concurrent imaging on lesion growth rate [n=7 (mean±SD: 2 mm/year±3.4 mm vs. 1.9 mm/year±3.6 mm)] over a period of at least two years as well as pathology data in connection to preoperative concurrent imaging were available in a small number of patients (n=7, p=0.933 for mean differences in maximal lesion diameter). MRI of the pancreas was more readily available and less expensive than EUS in an outpatient setting. In conclusion, MRI performs well compared to EUS for the detection and subsequent surveillance of MEN1-related panNENs larger than 10 mm and seems to be cost-effective. Both modalities could be used at initial assessment and MRI alone could be utilized thereafter in patient surveillance. EUS retains its value in surgical planning and the detection of small mostly functional PanNENs.

Assessment of serum-free cortisol levels in patients with adrenocortical carcinoma treated with mitotane: a pilot study.

OBJECTIVE: Mitotane treatment in adrenocortical carcinoma (ACC) results in unreliable measurement of serum total cortisol (TC) levels because of an elevation in corticosteroid-binding globulin (CBG). DESIGN: The use of a newly-developed serum-free cortisol (FC) assay was assessed to investigate the characteristics of a more valid measure of cortisol status. PATIENTS: Sixty-two serum samples from patients with ACC treated with mitotane were studied. Different subgroups were studied according to mitotane levels (<14, 14-20 and >20 mg/dl), hydrocortisone replacement treatment, presence of Cushing's syndrome (CS) and adrenocorticotrophin (ACTH) levels. MEASUREMENTS: Serum FC was measured using a newly-developed assay, TC, CBG and plasma ACTH using conventional laboratory kits; TC-to-CBG (Free cortisol index, FCI, nmol/mg) and TC-to-FC (TFR) ratios were calculated. RESULTS: CBG levels were elevated and positively correlated to mitotane levels. FC was positively related to TC and FCI in nearly all subgroups studied. Plasma ACTH was negatively related to parameters of cortisol levels in the total samples studied. In the 'target' subgroup with normal ACTH levels and mitotane levels 14-20 mg/dl, no correlation of plasma ACTH with any parameter studied was seen, and FC suggested over-replacement with hydrocortisone treatment in the subgroup with CS. CONCLUSIONS: FC measurement may offer additional information in the follow-up of patients on mitotane, especially when there is a history of CS which invalidates the use of acute changes in plasma ACTH as a parameter of hydrocortisone replacement. These preliminary data suggest that it may prove useful as a biochemical marker when TC or FCI are invalidated by mitotane treatment or plasma ACTH is suppressed by hypercortisolaemia. Larger studies are needed to substantiate the clinical utility of FC measurement in specific groups of patients.