| 1. |
- Bjornsdottir, Sigridur, et al.
(författare)
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Drug Prescription Patterns in Patients With Addison's Disease : A Swedish Population-Based Cohort Study
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:5, s. 2009-2018
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Tidskriftsartikel (refereegranskat)abstract
- Context: There are no published data on drug prescription in patients with Addison's disease ( AD). Objective: Our objective was to describe the drug prescription patterns in Swedish AD patients before and after diagnosis compared with population controls. Design and Setting: We conducted a population-based cohort study in Sweden. Patients: Through the Swedish National Patient Register and the Swedish Prescribed Drug Register, we identified 1305 patients with both a diagnosis of AD and on combination treatment with hydrocortisone/cortisone acetate and fludrocortisone. Direct evidence of the AD diagnosis from patient charts was not available. We identified 11 996 matched controls by the Register of Population. Main Outcome Measure: We determined the ratio of observed to expected number of patients treated with prescribed drugs. Results: Overall, Swedish AD patients received more prescribed drugs than controls, and 59.3% of the AD patients had medications indicating concomitant autoimmune disease. Interestingly, both before and after the diagnosis of AD, patients used more gastrointestinal medications, antianemic preparations, lipid-modifying agents, antibiotics for systemic use, hypnotics and sedatives, and drugs for obstructive airway disease (all P values < .05). Notably, an increased prescription of several antihypertensive drugs and high-ceiling diuretics was observed after the diagnosis of AD. Conclusion: Gastrointestinal symptoms and anemia, especially in conjunction with autoimmune disorders, should alert the physician about the possibility of AD. The higher use of drugs for cardiovascular disorders after diagnosis in patients with AD raises concerns about the replacement therapy.
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| 2. |
- Björnsdottir, Sigridur, et al.
(författare)
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Addison's Disease in Women Is a Risk Factor for an Adverse Pregnancy Outcome
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:12, s. 5249-5257
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Tidskriftsartikel (refereegranskat)abstract
- Context: Autoimmune Addison's disease(AAD) tends to affect young and middle-aged women. It is not known whether the existence of undiagnosed or diagnosed AAD influences the outcome of pregnancy. Objective: The aim of the study was to compare the number of children and pregnancy outcomes in individuals with AAD and controls. Design and Setting: We conducted a population-based historical cohort study in Sweden. Patients: Through the Swedish National Patient Register and the Total Population Register, we identified 1,188 women with AAD and 11,879 age-matched controls who delivered infants between 1973 and 2006. Main Outcome Measures: We measured parity and pregnancy outcome. Results: Adjusted odds ratios (ORs) for infants born to mothers with deliveries 3 yr or less before the diagnosis of AAD were 2.40 [95% confidence interval (Cl), 1.27-4.53] for preterm birth (<= 37 wk), 3.50 (95% Cl, 1.83-6.67) for low birth weight (<2500 g), and 1.74 (95% Cl, 1.02-2.96) for cesarean section. Compared to controls, women who gave birth after their AAD diagnosis were at increased risk of both cesarean delivery (adjusted OR, 2.35; 95% Cl, 1.68-3.27) and preterm delivery (adjusted OR, 2.61; 95% Cl, 1.69-4.05). Stratifying by isolated AAD and concomitant type 1 diabetes and/or autoimmune thyroid disease in the mother did not essentially influence these risks. There were no differences in risks of congenital malformations or infant death. Women with AAD had a reduced overall parity compared to controls (P < 0.001). Conclusion: Clinically undiagnosed and diagnosed AAD both entail increased risks of unfavorable pregnancy outcomes. AAD also influences the number of childbirths.
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| 3. |
- Bothou, Christina, et al.
(författare)
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Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency : Experience from a Multicenter Survey
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8
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Tidskriftsartikel (refereegranskat)abstract
- Context: Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment.Objective: Multicenter survey on current clinical approaches in managing AI during pregnancy.Design: Retrospective anonymized data collection from 19 international centers from 2013 to 2019.Setting and patients: 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%).Results: Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes.Conclusions: This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.
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| 4. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 5. |
- Eriksson, Daniel, et al.
(författare)
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Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1
- 2018
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:1, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.
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| 6. |
- Oksnes, Marianne, et al.
(författare)
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Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of addison's disease : a randomized clinical trial
- 2014
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 99:5, s. 1665-1674
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Conventional glucocorticoid replacement therapy fails to mimic the physiological cortisol rhythm, which may have implications for morbidity and mortality in patients with Addison's disease.OBJECTIVE: The objective of the study was to compare the effects of continuous sc hydrocortisone infusion (CSHI) with conventional oral hydrocortisone (OHC) replacement therapy.DESIGN, PATIENTS, AND INTERVENTIONS: This was a prospective crossover, randomized, multicenter clinical trial comparing 3 months of treatment with thrice-daily OHC vs CSHI. From Norway and Sweden, 33 patients were enrolled from registries and clinics. All patients were assessed at baseline and after 8 and 12 weeks in each treatment arm.MAIN OUTCOME MEASURES: The morning ACTH level was the primary outcome measure. Secondary outcome measures were effects on metabolism, health-related quality of life (HRQoL), sleep, and safety.RESULTS: CSHI yielded normalization of morning ACTH and cortisol levels, and 24-hour salivary cortisol curves resembled the normal circadian variation. Urinary concentrations of glucocorticoid metabolites displayed a normal pattern with CSHI but were clearly altered with OHC. Several HRQoL indices in the vitality domain improved over time with CSHI. No benefit was found for either treatments for any subjective (Pittsburgh Sleep Quality Index questionnaire) or objective (actigraphy) sleep parameters.CONCLUSION: CSHI safely brought ACTH and cortisol toward normal circadian levels without adversely affecting glucocorticoid metabolism in the way that OHC did. Positive effects on HRQoL were noted with CSHI, indicating that physiological glucocorticoid replacement therapy may be beneficial and that CSHI might become a treatment option for patients poorly controlled on conventional therapy.
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| 7. |
- Papakokkinou, Eleni, et al.
(författare)
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Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
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Tidskriftsartikel (refereegranskat)abstract
- Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.Objective: To investigate comorbidities in patients with CD.Design, setting, and patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Main outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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| 8. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study
- 2019
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 104:6, s. 2375-2384
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Tidskriftsartikel (refereegranskat)abstract
- Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. Design, Patients, and Methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. Results: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. Conclusion: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
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| 9. |
- Sævik, Åse Bjorvatn, et al.
(författare)
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Residual Corticosteroid Production in Autoimmune Addison Disease
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:7, s. 2430-2441
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Tidskriftsartikel (refereegranskat)abstract
- Context: Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis.Objective: To determine frequencies and clinical features of residual corticosteroid production in patients with AAD.Design: Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography-tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test.Results: Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = -0.487; P < 0.001).Conclusion: In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.
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| 10. |
- Skov, Jakob, et al.
(författare)
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Limited Genetic Overlap Between Overt Hashimoto's Thyroiditis and Graves' Disease in Twins : A Population-based Study
- 2021
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 106:4, s. 1101-1110
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Tidskriftsartikel (refereegranskat)abstract
- Context: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are known to coaggregate in families, but the magnitude and nature of a shared etiology is unknown.Objectives: To estimate the shared genetic influence on overt HT and GD and to examine if the heritability differs between men and women. Design, setting, and patients: We used national health registries to identify cases of HT and GD in a cohort of 110 814 Swedish twins. By comparing intra-class and cross-twin cross-trait correlations in dizygotic and monozygotic twins, we calculated heritability and the proportions thereof shared between the diseases. Univariate estimates of heritability were calculated by sex.Results: The heritability for HT and GD was 65% (95% CI, 61-70) and 63% (95% CI, 55-72), respectively. The genetic correlation was 0.35 (95% CI, 0.20-0.50) and shared genetic effects accounted for 8% of the variance for both HT and GD. Univariate heritability was significantly higher in men than in women for HT (90% vs 60%, P < 0.001) but not for GD (79% vs 63%, P = 0.085).Conclusions: From a genetic perspective, HT and GD appear to be only modestly related diseases. Hence, the term "autoimmune thyroid disease," used to cluster these disorders, may have limited validity in a genetic context. Moreover, the mechanisms contributing to HT are partly different for the sexes, with genetic components more important in men.
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