Context: Primary adrenal insufficiency (Addison's disease) is a rare autoimmune disease. Until recently, life expectancy in Addison's disease patients was considered normal. Objective: To determine the mortality rate in Addison's disease patients. Design and methods: i) Patients registered with Addison's disease in Norway during 1943-2005 were identified through search in hospital diagnosis registries. Scrutiny of the medical records provided diagnostic accuracy and age at diagnosis. ii) The patients who had died were identified from the National Directory of Residents. iii) Background mortality data were obtained from Statistics Norway, and standard mortality rate (SMR) calculated. iv) Death diagnoses were obtained from the Norwegian Death Cause Registry. Results: Totally 811 patients with Addison's disease were identified, of whom 147 were deceased. Overall SMR was 1.15 (95% confidence intervals (CI) 0.96-1.35), similar in females (1.18 (0.92-1.44)) and males (1.10 (0.80-1.39)). Patients diagnosed before the age of 40 had significantly elevated SMR at 1.50 (95% CI 1.09-2.01), most pronounced in males (2.03 (1.19-2.86)). Acute adrenal failure was a major cause of death; infection and sudden death were more common than in the general population. The mean ages at death for females (75.7 years) and males (64.8 years) were 3.2 and 11.2 years less than the estimated life expectancy. Conclusion: Addison's disease is still a potentially lethal condition, with excess mortality in acute adrenal failure, infection, and sudden death in patients diagnosed at young age. Otherwise, the prognosis is excellent for patients with Addison's disease.
ObjectiveLow serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health.MethodsDNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994–1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007–2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level.ResultsA total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1)) there was a significant association with breast cancer (P<0.05).ConclusionOur results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency.Trial RegistrationClinicalTrials.gov NCT01395303
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