| 1. |
- 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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| 2. |
- Brozzetti, A, et al.
(författare)
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Autoantibody response against NALP5/MATER in primary ovarian insufficiency and in autoimmune Addison's disease
- 2015
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:5, s. 1941-1948
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Tidskriftsartikel (refereegranskat)abstract
- Context:NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (MATER) is an autoantigen in hypoparathyroidism associated with autoimmune polyendocrine syndrome type 1 (APS1) but is also expressed in the ovary. Mater is an autoantigen in experimental autoimmune oophoritis.Objectives:The objectives of the study were to determine the frequency of NALP5/MATER autoantibodies (NALP5/MATER-Ab) in women with premature ovarian insufficiency (POI) and in patients with autoimmune Addison's disease (AAD) and to evaluate whether inhibin chains are a target for autoantibodies in POI.Methods:Autoantibodies against NALP5/MATER and inhibin chains-α and -βA were determined by radiobinding assays in 172 patients with AAD without clinical signs of gonadal insufficiency, 41 women with both AAD and autoimmune POI [steroidogenic cell autoimmune POI (SCA-POI)], 119 women with idiopathic POI, 19 patients with APS1, and 211 healthy control subjects.Results:NALP5/MATER-Ab were detected in 11 of 19 (58%) sera from APS1 patients, 12 of 172 (7%) AAD sera, 5 of 41 (12%) SCA-POI sera, 0 of 119 idiopathic POI sera and 1 of 211 healthy control sera (P < .001). None of 160 POI sera, including 41 sera from women with SCA-POI and 119 women with idiopathic POI, and none of 211 healthy control sera were positive for inhibin chain-α/βA autoantibodies.Conclusions:NALP5/MATER-Ab are associated with hypoparathyroidism in APS1 but are present also in patients with AAD and in women with SCA-POI without hypoparathyroidism. Inhibin chains do not appear to be likely candidate targets of autoantibodies in human POI.
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| 3. |
- 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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| 4. |
- Elfström, Peter, 1974-, et al.
(författare)
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Risk of primary adrenal insufficiency in patients with celiac disease
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Chevy Chase, Md. : Endocrine Society. - 0021-972X .- 1945-7197. ; 92:9, s. 3595-3598
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Earlier research has suggested a positive association between Addison’s disease (AD) and celiac disease (CD).Wehave here investigated the risk of AD in individuals with CD from a general population cohort.Methods: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964–2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD.Results: There was a statistically significantly positive association between CD and subsequent AD [HR _ 11.4; 95% confidence interval (CI) _ 4.4 –29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI _ 1.9 –11.4). Individuals with prior AD were at increased risk of CD (odds ratio _ 8.6; 95% CI _ 3.4 –21.8).Conclusions: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.
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| 5. |
- Elfström, Peter, 1974-, et al.
(författare)
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Risk of Thyroid Disease in Individuals with Celiac Disease
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:10, s. 3915-3921
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been suggested that celiac disease is associated with thyroid disease. Earlier studies, however, have been predominately cross-sectional and have often lacked controls. There is hence a need for further research. In this study, we estimated the risk of thyroid disease in individuals with celiac disease from a general population cohort.Methods: A total of 14,021 individuals with celiac disease (1964–2003) and a matched reference population of 68,068 individuals were identified through the Swedish national registers. Cox regression estimated the risk of thyroid disease in subjects with celiac disease. Analyses were restricted to individuals with a follow-up ofmorethan 1 yr and withnothyroid disease before study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for subsequent celiac disease in individuals with thyroid disease.Results: Celiac disease was positively associated with hypothyroidism [hazard ratio (HR)_4.4;95% confidence interval (CI) _ 3.4 –5.6; P _ 0.001], thyroiditis (HR _ 3.6; 95% CI _1.9–6.7; P _ 0.001) and hyperthyroidism (HR_2.9;95%CI_2.0–4.2; P_0.001). The highest risk estimates were found in children (hypothyroidism, HR _ 6.0 and 95% CI _ 3.4 –10.6; thyroiditis, HR _ 4.7 and 95% CI _ 2.1–10.5; hyperthyroidism, HR _ 4.8 and 95% CI _ 2.5–9.4). In post hoc analyses, where the reference population was restricted to inpatients, the adjusted HR was 3.4 for hypothyroidism (95% CI_2.7– 4.4; P_0.001), 3.3 for thyroiditis(95%CI_1.5–7.7; P_0.001), and 3.1 for hyperthyroidism (95% CI _ 2.0–4.8; P _ 0.001).Conclusion: Celiac disease is associated with thyroid disease, and these associations were seen regardless of temporal sequence. This indicates shared etiology and that these individuals are more susceptible to autoimmune disease.
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| 6. |
- 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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| 7. |
- Gylling, Mikhail, et al.
(författare)
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The hypoparathyroidism of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protective effect of male sex
- 2003
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X .- 1945-7197. ; 88:10, s. 4602-4608
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, hypoparathyroidism (HP) is the most common endocrine component. It occurs in most (but not all) patients. Determinants of its occurrence are unknown, and there is no proof for its autoimmune nature. Recently, the Ca(2+)-sensing receptor (CaSR) was reported to be an autoantigen in HP. With our group of 90 patients, we aimed at identifying the determinants and pathomechanism of HP. For the determinants, we evaluated gender and the HLA class II. For the pathomechanism, we searched for parathyroid autoantibodies, including antibodies against CaSR and PTH. Also, we studied whether AIRE is expressed in the human parathyroid, because its absence could be a pathogenetic factor. We found a clear gender linkage with lower and later incidence in males. Of the 14 patients who had escaped HP, 13 were males. This was associated with adrenal failure, which was the first or only endocrinopathy in 47% of males vs. 7% of females. In contrast, we found no linkage to the HLA class II. By immunofluorescence, 19% of the patients had antibodies to parathyroid epithelia. By immunoblotting, these recognized several parathyroid proteins. No antibodies were observed against the CaSR or PTH. By RT-PCR, AIRE mRNA was not found in the parathyroid.
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| 8. |
- Halonen, M, et al.
(författare)
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AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype
- 2002
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X .- 1945-7197. ; 87:6, s. 2568-
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, OMIM 240300) is a rare autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21q22.3. This monogenic disease provides an interesting model for studies of other common and more complex autoimmune diseases. The most common components of APECED are chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison’s disease, but several other endocrine deficiencies and ectodermal dystrophies also occur and the phenotype varies widely. The AIRE genotype also varies; 42 different mutations have been reported so far. To understand the complexity of the phenotype, we studied the AIRE and human leukocyte antigen (HLA) class II genotypes in a series of patients with APECED. The only association between the phenotype and the AIRE genotype was the higher prevalence of candidiasis in the patients with the most common mutation, R257X, than in those with other mutations. Addison’s disease was associated with HLA-DRB1*03 (P = 0.021), alopecia with HLA-DRB1*04- DQB1*0302 (P < 0.001), whereas type 1 diabetes correlated negatively with HLA-DRB1*15-DQB1*0602 (P = 0.036). The same HLA associations have previously been established for non-APECED patients. We conclude that mutation of AIRE per se has little influence on the APECED phenotype, whereas, in contrast to earlier reports, HLA class II is a significant determinant.
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| 9. |
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| 10. |
- Lovas, K, et al.
(författare)
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Replacement of dehydroepiandrosterone in adrenal failure : no benefit forsubjective health status and sexuality in a 9-month, randomized, parallelgroup clinical trial
- 2003
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 88:3, s. 1112-
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Tidskriftsartikel (refereegranskat)abstract
- The physiological role of dehydroepiandrosterone (DHEA) is not well understood, but studies suggest positive effects on subjective health and bone metabolism. We have conducted a clinical trial with DHEA replacement in adrenal failure with the primary aim of evaluating effects on subjective health status and sexuality. Thirty-nine women with adrenal failure were randomized to 9 months of treatment with 25 mg DHEA (n = 19) or placebo (n = 20). Treatment effects were assessed by validated questionnaires of subjective health and sexuality. DHEA replacement yielded a wide variation of effects on the subjective health scales, which were not different from the effects of placebo. Almost all patients receiving DHEA obtained normal androgen levels. Eighty-nine percent of the patients receiving DHEA experienced side-effects, in particular increased sweat odor and scalp itching. DHEA replacement did not significantly change the levels of blood lipids, IGF-I, and markers of bone metabolism. In conclusion, we do not find evidence of beneficial effects of DHEA on subjective health status and sexuality in adrenal failure. However, DHEA may be beneficial for subgroups of patients with adrenal failure, but these remain to be identified. Premenopausal androgen levels can be restored with 25 mg DHEA daily in most female patients, but side-effects are frequent.
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