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.
The aim of the study was to compare the number of children and pregnancy outcomes in individuals with AAD and controls.
We conducted a population-based historical cohort study in Sweden.
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.
We measured parity and pregnancy outcome.
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 (CI), 1.27-4.53] for preterm birth (=37 wk), 3.50 (95% CI, 1.83-6.67) for low birth weight (
Autoimmune destruction of the adrenal cortex is the most common cause of primary adrenocortical insufficiency (Addison's disease) in industrialized countries. We have investigated a large Norwegian cohort of patients with Addison's disease in terms of clinical manifestations, autoantibodies, and human leukocyte antigen (HLA) class II haplotypes. The study comprised 94 patients (54 females) of ages 6-85 yr (mean 45 yr) with, either isolated Addison's disease or part of autoimmune polyendocrine syndrome type II. Among those diagnosed before the age of thirty, 53% were men, while among those diagnosed at 30 or above, 30% were men. Altogether 77 (82%) of the 94 patients had autoantibodies against 21-hydroxylase (21OH). Thirty-eight of the 40 patients with disease duration 5 yr or less had such autoantibodies. This frequency fell to 60% among patients with a disease duration greater than 35 yr. Five women had gonadal failure. This failure correlated with antibodies against side-chain cleavage enzyme (P = 0.03). Antibodies against glutamic acid decarboxylase and IA2 correlated with the presence of type 1 diabetes (P
Studies of the clinical and immunological features of autoimmune Addison disease (AAD) are needed to understand the disease burden and increased mortality.
To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles, and cardiovascular risk factors.
A cross-sectional, population-based study that included 660 AAD patients from the Swedish Addison Registry (2008-2014). When analyzing the cardiovascular risk factors, 3594 individuals from the population-based survey in Northern Sweden, MONICA (monitoring of trends and determinants of cardiovascular disease), served as controls.
The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.
The proportion of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had =1 associated autoimmune diseases, more frequently coexisting in females (P
There are no published data on drug prescription in patients with Addison's disease (AD).
Our objective was to describe the drug prescription patterns in Swedish AD patients before and after diagnosis compared with population controls.
We conducted a population-based cohort study in Sweden.
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.
We determined the ratio of observed to expected number of patients treated with prescribed drugs.
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
The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In this study, we examined the heritability of AAD and explored disease-associated autoimmune comorbidity among Swedish twins.
A population-based longitudinal cohort of 112,100 Swedish twins was used to calculate the heritability of AAD, and to explore co-occurrence of 10 organ-specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected 1964-2012 through linkage to the Swedish National Patient Register. The Swedish Prescribed Drug Register was used for additional diagnostic precision. When available, biobank serum samples were used to ascertain the AAD diagnosis through identification of 21-hydroxylase autoantibodies.
We identified 29 twins with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15) dizygotic pairs were concordant for AAD. The probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD displayed a higher degree of similarity than those of dizygotic twins, with an incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune diagnoses within pairs.
The heritability of AAD appears to be very high, emphasizing the need for further research on the genetic etiology of the disease. Monozygotic twin concordance for multiple autoimmune manifestations suggests strong genetic influence on disease specificity in organ-specific autoimmunity.
We determined the incidence and prevalence of Addison's disease (AD) among persons with or without type 1 diabetes mellitus (T1DM) in nationwide, matched cohort studies.
Persons with T1DM were identified from the Swedish National Diabetes Register and each was matched for age, sex, year and county to five controls randomly selected from the general population. Persons with AD were identified from the Swedish National Inpatient Register. Baseline demographics and seasonal onset variation of AD were presented by descriptive statistics. Prevalence and incidence were estimated by proportions and incidence rates, respectively. Times to AD were analyzed using the Cox proportional hazard model.
Between 1998 and 2013, 66 persons with T1DM were diagnosed with AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM, while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570 controls. The difference in mean age at diagnosis of AD between the groups was 6.3 years (P value?=?0.036). The incidence of AD for a person with or without T1DM was therefore 193 and 18 per million person-years, respectively. The adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1-16.5). The highest incidence of AD was observed during February-March and September-October. The prevalence of AD in persons with or without T1DM in December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD in persons with T1DM vs controls was 16.5 (95% CI: 11.1-24.5).
The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern.
Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population.
A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964-2004.
Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR).
A more than 2-fold increased mortality risk was observed in both women (SMR 2.9, 95% CI 2.7-3.0) and men (SMR 2.5, 95% CI 2.3-2.7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4.6, 95% CI 3.5-6.0) compared with patients with APS2 (SMR 2.1, 95% CI 1.9-2.4). Cancer incidence was increased (SIR 1.3, 95% CI 1.2-1.5). When tumours observed during the first year of follow-up were excluded, only the cancer risk among APS1 patients remained increased. Cause-specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population.
Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency.
OBJECTIVE: To investigate the risk of affective disorders among patients hospitalised with adrenocortical insufficiency in the study period: 1977-1999. METHOD: Using data from Danish registers, two study cohorts were identified by their ICD diagnoses at discharge from hospital: one comprising all patients with a first hospital admission with an index diagnosis of adrenocortical insufficiency; the other a control cohort comprising all patients with a first hospital admission with an index diagnosis of osteoarthritis. Subsequent admissions to psychiatric hospital wards with discharge ICD diagnoses of affective disorders were used as events of interest. Rates of readmission were estimated using Poisson regression models in survival analyses. Age, sex, duration of time after index discharge, and calendar time were included as co-variables. The primary analysis included all patients with adrenocortical insufficiency. Thereafter, the subgroup of patients with primary adrenocortical insufficiency (Addison's disease) was investigated separately in a secondary analysis. RESULTS: A study sample of 989 patients with adrenocortical insufficiency and 124,854 patients with osteoarthritis was identified. Eight hundred and fifty-two patients were subsequently readmitted with a diagnosis of affective disorder. Patients with adrenocortical insufficiency had a 2.68 (95% CI: 1.62-4.42) times greater rate of affective disorders and a 2.12 (95% CI: 1.16-3.86) times greater rate of depressive disorder when compared with the rate for patients with osteoarthritis. Patients with Addison's disease had a 2.14 (95% CI: 1.14-4.03) times greater rate of affective disorders, and a 1.71 (95% CI: 0.81-3.63) times greater rate of depressive disorder compared with the rate of patients with osteoarthritis. CONCLUSION: Patients with adrenocortical insufficiency may be at increased risk of developing severe affective disorders. Conventional replacement therapy with hydrocortisone may not be sufficient to ensure the psychiatric well-being of these patients.
The results of studies of bone mineral density in Addison's disease (AD) are inconsistent. There are no published data on hip fracture risk in patients with AD. In this study, we compare hip fracture risk in adults with and without AD.
A population-based cohort study.
Through the Swedish National Patient Register and the Total Population Register, we identified 3219 patients without prior hip fracture who were diagnosed with AD at the age of =30 years during the period 1964-2006 and 31 557 age- and sex-matched controls. Time to hip fracture was measured.
We observed 221 hip fractures (6.9%) in patients with AD and 846 (2.7%) in the controls. Patients with AD had a higher risk of hip fracture [hazard ratio (HR) = 1.8; 95% confidence interval (CI), 1.6-2.1; P