Hypercalcemic crisis is a severe but rare complication of primary hyperparathyroidism (PHPT), and data on denosumab treatment of patients with this disease is still very limited. The aim of this paper is to investigate the hypocalcemic effect of denosumab in PHPT patients with severe hypercalcemia when surgery should be delayed or is impossible for some reasons. We performed a retrospective study of 10 patients. The analysis included the use of biochemical markers of calcium-phosphorus metabolism, which were followed after the administration of 60 mg of denosumab. The trend to calcium reduction was already determined on the 3rd day after denosumab administration. In most cases the decrease in serum calcium level to the range of 2.8 mmol/L on average or lower was observed on the 7th day (p=0.002). In addition to a significant increase in calcium levels we confirmed a significant increase in the estimated glomerular filtration rate on 7th day (p=0.012). After that, 7 patients underwent successful parathyroidectomy and achieved eucalcemia or hypocalcemia, one patient developed the recurrence of parathyroid cancer after initial surgery, while two patients with severe cardiovascular pathology refused surgery. Our study shows that denosumab is a useful tool in PHPT-associated hypercalcemia before surgery or if surgery is contraindicated.

IntroductionChronic hypoparathyroidism is a relatively rare disease associated with multicomponent medical therapy and various complications. The analysis of large databases of patients with chronic hypoparathyroidism is a necessary tool to enhance quality of medical care, as well as to determine the optimal clinical and therapeutic approaches, and prognostic markers of the disease.The Aimof this study is to estimate the clinical and biochemical profile, long-term complications, medical therapy and disease control of the patients with chronic postsurgical and non-surgical hypoparathyroidism.Materials and Methodsthe cross-sectional, observational, continuous study was based on the Russian Registry of patients with hypoparathyroidism. 544 patients from 63 regions of the Russian Federation were included in this study.ResultsThe majority of cases had postsurgical etiology (88.4%). Postsurgical hypoparathyroidism prevailed in females (р<0.001). About a half of patients had blood calcium and phosphorus targets, 56 and 52% respectively. Nephrolithiasis was confirmed in 32.5%, nephrocalcinosis - in 12.3% of cases. The risk of nephrocalcinosis/nephrolithiasis increased by 1.85 times with disease duration more than 4.5 years. The cataract was found in 9.4%. The cut-off point for the development of cataracts was 9.5 years, with a 6.96-fold increased risk. The longer duration of hypoparathyroidism of any etiology was associated with more frequent cataract (p=0.0018).We found brain calcification in 4%, arrhythmias in 7.2% and neuropsychiatric symptoms in 5.15% of cases. Generally, the BMD in the studied group corresponded to age values, and there was no evidence for the phenomenon of high bone density. TBS was consistent with normal bone microarchitectonics. In our study, the majority of patients (83.5%) was treated with standard therapy of calcium and vitamin D supplements. 5 patients with severe disease course were treated with rhPTH (1–34).ConclusionsAnalysis of the presented database indicates insufficient diagnosis of the complications associated with chronic hypoparathyroidism. Overall, hypoparathyroidism is associated with higher risks of renal stone formation, decreased GFR, cataract especially in patients with longer duration of disease.

The aimTo study the association of demographic, clinical, and laboratory factors and the use of glucose-lowering drugs and anti-coronavirus disease (COVID-19) vaccination with the COVID-19-related case fatality rate (CFR) in diabetes mellitus (DM) patients.MethodsThis study is a nationwide observational cohort study based on the data from the National Diabetes Register (NDR) that is the database containing online clinical information about the population with DM. The outcomes (death or recovery) for COVID-19 were registered in 235,248 patients with DM [type 1 diabetes mellitus (T1DM), n = 11,058; type 2 diabetes mellitus (T2DM), n = 224,190] from March 20, 2020, until November 25, 2021. The unadjusted odds ratio (OR) and 95% confidence interval (CI) were used to estimate the risk factors for CFR. Then the ranging of significant factors was performed and the most vulnerable groups of factors for the lethal outcome were chosen.ResultsThe CFR due to COVID-19 was 8.1% in T1DM and 15.3% in T2DM. Increased CFR was associated with the male population [OR = 1.25 (95% CI: 1.09–1.44) in T1DM and 1.18 (95% CI: 1.15–1.21) in T2DM], age ≥65 years [OR = 4.44 (95% CI: 3.75–5.24) in T1DM and 3.18 (95% CI: 3.09–3.26) in T2DM], DM duration ≥10 years [OR = 2.46 (95% CI: 2.06–2.95) in T1DM and 2.11 (95% CI: 2.06–2.16) in T2DM], body mass index (BMI) ≥30 kg/m2 [OR = 1.95 (95% CI: 1.52–2.50)] in T1DM, HbA1c ≥7% [OR = 1.35 (95% CI: 1.29–1.43)] in T2DM. The atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD) were associated with higher CFR in T1DM but not in T2DM. The pre-COVID-19 glucose-lowering therapy in T2DM was differently associated with CFR (OR): 0.61 (95% CI: 0.59–0.62) for metformin, 0.59 (95% CI: 0.57–0.61) for dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), 0.46 (95% CI: 0.44–0.49) for sodium-glucose co-transporter-2 (SGLT2) inhibitors, 0.38 (95% CI: 0.29–0.51) for glucagon-like peptide-1 receptor agonists (arGLP-1), 1.34 (95% CI: 1.31–1.37) for sulfonylurea (SU), and 1.47 (95% CI: 1.43–1.51) for insulin. Anti-COVID-19 vaccination was associated with a lower fatality risk in both DM types: OR = 0.07 (95% CI: 0.03–0.20) in T1DM and OR = 0.19 (95% CI: 0.17–0.22) in T2DM.ConclusionsThe results of our study suggest that increased COVID-19-related fatality risk in both T1DM and T2DM patients associated with the male population, older age, longer DM duration, and absence of anti-COVID-19 vaccination. In T2DM, pre-COVID-19 glucose-lowering therapy with metformin, DPP-4 inhibitors, SGLT2 inhibitors, and arGLP-1 had a positive effect on the risk of death. The most vulnerable combination of risk factors for lethal outcome in both DM types was vaccine absence + age ≥65 years + DM duration ≥10 years.

Parathyroid carcinoma (PC) is a rare and aggressive malignancy, accounting for less than 1% of primary hyperparathyroidism (PHPT) and only 0.005% of all cancers. 1,2 Five-year survival rates, as pooled from different registries and case series, are in the range of 76%-85%, with 10-year survival rates being between 49% and 77%. 3,4 Recurrence occurs in more than half of PC cases, with the five-year survival rate in patients with metastatic disease being less than 50%. 5,6 Reports from the United States, Australia, Finland and the

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