Epidemiology and health related quality of life in hypoparathyroidism in Norway.

OBJECTIVE: The epidemiology of hypoparathyroidism (HP) is largely unknown. We aimed to determine prevalence, etiologies, health related quality of life (HRQoL) and treatment pattern of HP. METHODS: Patients with HP and 22q11 deletion syndrome (DiGeorge syndrome) were identified in electronic hospital registries. All identified patients were invited to participate in a survey. Among patients who responded, HRQoL was determined by Short Form 36 (SF-36) and Hospital Anxiety and Depression scale (HADS). Autoantibodies were measured and candidate genes (CaSR, AIRE, GATA3 and 22q11-deletion) were sequenced for classification of etiology. RESULTS: We identified 522 patients (511 alive) and estimated overall prevalence at 102 per million divided among post-surgical HP (64 per million), non-surgical HP (30 per million) and pseudo-HP (8 per million). Non-surgical HP comprised autosomal dominant hypocalcemia (21%), autoimmune polyendocrine syndrome type 1 (17%), DiGeorge/22q11 deletion syndrome (15%), idiopathic HP (44%), and others, 4%. Among the 283 respondents (median age 53 years (range 9-89), 75% females), seven formerly classified as idiopathic were reclassified after genetic and immunological analyses, whereas 26 (17% of non-surgical HP) remained idiopathic. Most were treated with vitamin D (94%) and calcium (70%), and 10 received parathyroid hormone. HP patients scored significantly worse than the normative population on SF-36 and HADS; patients with post-surgical scored worse than those with non-surgical HP and pseudo-HP, especially on physical health. CONCLUSIONS: We found higher prevalence of non-surgical HP in Norway than reported elsewhere. Genetic testing and autoimmunity screening of idiopathic HP identified a specific cause in 21%. Further research is necessary to unravel the causes of idiopathic HP and to improve the reduced HRQoL reported by HP patients

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.Metabolic health: pathophysiological trajectories and therap

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Precursors to P'P' and upper mantle discontinuities

In this paper the origin of precursors to P' P' with lead times greater than 50 s is investigated. Good NORSAR records of P'650P' and P'400P' for these arrivals as well as corresponding slowness estimates are presented. These phases are interpreted as done by others in terms of underside reflections from discontinuities or sharp transition zones in the upper mantle. An extensive search of 5 years of NORSAR records did not produce any significant evidence on P' P' precursor arrivals with lead times greater than 50 s other than those mentioned above.           ARK: https://n2t.net/ark:/88439/y030873 Permalink: https://geophysicsjournal.com/article/255 &nbsp

High-dose vitamin D in Addison's disease regulates T-cells and monocytes. A pilot trial

Objectives On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD). Methods This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable. The primary outcome measures were changes in 25-hydroxyvitamin D3 (25(OH)D3) levels and immune cells including T helper cells (Th; CD3+CD4+), late-activated Th cells (CD3+CD4+HLA-DR+), regulatory T cells (CD3+CD4+CD25brightCD127dim/neg), cytotoxic T cells (Tc; CD3+CD8+), late-activated Tc cells (CD3+CD8+HLA-DR+), and monocytes. The explorative analysis included the correlation of changes with VD-related gene polymorphisms and 21-hydroxylase antibody titers. Results Ten of 13 patients (77%) were VD deficient. Median 25(OH)D3 concentrations increased significantly to 41.5 ng/ml (median changes: 19.95 ng/ml; P = 0.0005) after 3 mo of cholecalciferol treatment. Within the T-cells, only the late-activated Th (median changes: 1.6%; P = 0.02) and late-activated Tc cells (median changes: 4.05%; P = 0.03) decreased, whereas monocytes (median changes: 1.05%; P = 0.008) increased after VD therapy. T-cell changes were associated with two polymorphisms (CYP27B1-rs108770012 and VDR-rs10735810), but no changes in the 21-hydroxylase antibody titers were observed. Conclusions Three months of treatment with cholecalciferol achieved sufficient 25(OH)D3 levels and can regulate late-activated T-cells and monocytes in patients with AD. Explorative analysis revealed potential genetic contributions. This pilot trial provides novel insights about immunomodulation in AD