| 1. |
- Nowotny, H, et al.
(författare)
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Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis
- 2021
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1559-0100 .- 1355-008X. ; 7371:23, s. 586-594
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Tidskriftsartikel (refereegranskat)abstract
- Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives.
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| 2. |
- Oster, S., et al.
(författare)
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Self-management and hospitalization in 615 Swedish patients with Addison's disease during the coronavirus disease 2019 pandemic: a retrospective study
- 2023
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 188:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective Autoimmune Addison's disease (AAD) entails a chronic adrenal insufficiency and is associated with an increased risk of severe infections. It is, however, unknown how patients with AAD were affected by the coronavirus disease 2019 (COVID-19) pandemic of 2020-2021. This study was aimed at investigating the incidence of COVID-19 in patients with AAD in Sweden, the self-adjustment of medications during the disease, impact on social aspects, and treatment during hospitalization. Additionally, we investigated if there were any possible risk factors for infection and hospitalization. Design and methods Questionnaires were sent out from April to October 2021 to 813 adult patients with AAD in the Swedish Addison Registry. The questionnaires included 55 questions inquiring about COVID-19 sickness, hospital care, medications, and comorbidities, focusing on the pre-vaccine phase. Results Among the 615 included patients with AAD, COVID-19 was reported in 17% of which 8.5% required hospital care. Glucocorticoid treatment in hospitalized patients varied. For outpatients, 85% increased their glucocorticoid dosage during sickness. Older age (P = .002) and hypertension (P = .014) were associated with an increased risk of hospital care, while younger age (P < .001) and less worry about infection (P = .030) were correlated with a higher risk of COVID-19. Conclusions In the largest study to date examining AAD during the COVID-19 pandemic, we observed that although one-fifth of the cohort contracted COVID-19, few patients required hospital care. A majority of the patients applied general recommended sick rules despite reporting limited communication with healthcare during the pandemic.
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| 3. |
- Aranda-Guillén, Maribel, et al.
(författare)
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A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies.
- 2023
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Ingår i: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p<2e-16), and 1.2 SD higher in the young patients compared with the old (p=3e-4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.
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| 4. |
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| 5. |
- Artaza, Haydee, et al.
(författare)
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Rare copy number variation in autoimmune Addison's disease
- 2024
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is a rare but life-threatening endocrine disorder caused by an autoimmune destruction of the adrenal cortex. A previous genome-wide association study (GWAS) has shown that common variants near immune-related genes, which mostly encode proteins participating in the immune response, affect the risk of developing this condition. However, little is known about the contribution of copy number variations (CNVs) to AAD susceptibility. We used the genome-wide genotyping data from Norwegian and Swedish individuals (1,182 cases and 3,810 controls) to investigate the putative role of CNVs in the AAD aetiology. Although the frequency of rare CNVs was similar between cases and controls, we observed that larger deletions (>1,000 kb) were more common among patients (OR = 4.23, 95% CI 1.85-9.66, p = 0.0002). Despite this, none of the large case-deletions were conclusively pathogenic, and the clinical presentation and an AAD-polygenic risk score were similar between cases with and without the large CNVs. Among deletions exclusive to individuals with AAD, we highlight two ultra-rare deletions in the genes LRBA and BCL2L11, which we speculate might have contributed to the polygenic risk in these carriers. In conclusion, rare CNVs do not appear to be a major cause of AAD but further studies are needed to ascertain the potential contribution of rare deletions to the polygenic load of AAD susceptibility.
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| 6. |
- Papakokkinou, Eleni, et al.
(författare)
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Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
- 2021
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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| 9. |
- Van't Westeinde, A., et al.
(författare)
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Increased Resting-State Functional Connectivity in Patients With Autoimmune Addison Disease
- 2024
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - 0021-972X .- 1945-7197. ; 109:3, s. 701-710
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Tidskriftsartikel (refereegranskat)abstract
- Context Individuals with autoimmune Addison disease (AAD) take replacement medication for the lack of adrenal-derived glucocorticoid (GC) and mineralocorticoid hormones from diagnosis. The brain is highly sensitive to these hormones, but the consequence of having AAD for brain health has not been widely addressed.Objective The present study compared resting-state functional connectivity (rs-fc) of the brain between individuals with AAD and healthy controls.Methods Fifty-seven patients with AAD (33 female) and 69 healthy controls (39 female), aged 19 to 43 years were scanned with 3-T magnetic resonance imaging (MRI).Results Independent component and subsequent dual regression analyses revealed that individuals with AAD had stronger rs-fc compared to controls in 3 networks: the bilateral orbitofrontal cortex (OFC), the left medial visual and left posterior default mode network. A higher GC replacement dose was associated with stronger rs-fc in a small part of the left OFC in patients. We did not find any clear associations between rs-fc and executive functions or mental fatigue.Conclusion Our results suggest that having AAD affects the baseline functional organization of the brain and that current treatment strategies of AAD may be one risk factor.
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