Clinical and Immunological Characteristics of Autoimmune Addison Disease: A Nationwide Swedish Multicenter Study.

Context: Studies of the clinical and immunological features of autoimmune Addison 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: 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. Main Outcome Measures: The endpoints were the prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined. Results: 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 < 0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of hypertension (P = 0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of the patients, with a mean dose of 28.1 ± 8.5 mg/d. The mean hydrocortisone equivalent dose normalized to the body surface was 14.8 ± 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a greater incidence of hypertension (P = 0.046). Conclusions: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients did not have an increased prevalence of overweight, hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high glucocorticoid replacement doses could be a risk factor for hypertension.

Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial.

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.

Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I.

The prevalence of autoantibodies against nine intracellular enzyme autoantigens, namely 21-hydroxylase, side-chain cleavage enzyme (SCC), 17 alpha-hydroxylase, glutamic acid decarboxylase 65, aromatic L-amino acid decarboxylase, tyrosine phosphatase-like protein IA-2, tryptophan hydroxylase (TPH), tyrosine hydroxylase, cytochrome P450 1A2, and against the extracellular calcium-sensing receptor, was assessed in 90 patients with autoimmune polyendocrine syndrome type I. A multivariate logistic regression analysis was performed for the presence of autoantibodies as independent predictors for different disease manifestations. Reactivities against 21-hydroxylase and SCC were associated with Addison's disease with odds ratios (ORs) of 7.8 and 6.8, respectively. Hypogonadism was exclusively associated with autoantibodies against SCC with an OR of 12.5. Autoantibodies against tyrosine phosphatase-like protein IA-2 were associated with insulin-dependent diabetes mellitus with an OR of 14.9, but with low sensitivity. Reactivities against TPH and, surprisingly, glutamic acid decarboxylase 65, were associated with intestinal dysfunction, with ORs of 3.9 and 6.7, respectively. TPH reactivity was the best predictor for autoimmune hepatitis, with an OR of 27.0. Hypoparathyroidism was not associated with reactivity against any of the autoantigens tested. No reactivity against the calcium-sensing receptor was found. Analysis of autoantibodies in autoimmune polyendocrine syndrome type I patients is a useful tool for establishing autoimmune manifestations of the disease as well as providing diagnosis in patients with suspected disease.

[APS I--a severe autoimmune disease with endocrine and non-endocrine symptoms]. / APS I--svår autoimmun sjukdom med endokrina och icke-endokrina symtom.

Autoimmune polyglandular syndrome type I (APS I) is an autosomal recessive disorder characterized by a combination of autoimmune manifestations affecting endocrine and non-endocrine organs. APS I usually presents in childhood. The three most common manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. At least two of these must be present to fulfill the diagnostic criteria of this syndrome. The spectrum of other associated diseases includes gonadal insufficiency, alopecia, vitiligo and chronic active hepatitis. APS I is caused by a mutation in the AIRE-gene (autoimmune regulator) located on chromosome 21. Analysis of specific autoantibodies against intracellular enzymes, particularly enzymes in the synthesis of steroids and neurotransmittors, can be used in the diagnosis of APS I and to predict different manifestations of the disease.