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Cited by 490Adrenal Hormones and DisordersHormonal and reproductive studiesHormonal Regulation and Hypertension

Premature Mortality in Patients with Addison’s Disease: A Population-Based Study

Bergthorsdottir, Ragnhildur, Leonsson-Zachrisson, Maria, Odén, Anders, Johannsson, Gudmundur·2006·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2006-0076
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Abstract

Background: The survival rate of patients with primary adrenal insufficiency (Addison’s disease) undergoing currently accepted replacement therapy is not known, although well-informed patients are considered to have a normal survival rate. In this study, we evaluated the mortality of patients with Addison’s disease in Sweden. Methods: A population-based, retrospective, observational study was performed, using the National Swedish Hospital and Cause of Death Registers, covering the period from 1987–2001. After a diagnosis of Addison’s disease, each patient was followed until the end of follow-up or death. Mortality was compared with that of the Swedish background population. Findings: We identified 1675 patients (995 women and 680 men) diagnosed with primary adrenal insufficiency. The average follow-up from initial diagnosis was 6.5 yr. Five hundred seven patients died during the study period compared with an expected 199. The risk ratio for all-cause mortality was 2.19 (confidence interval 1.91–2.51) for men and 2.86 (confidence interval 2.54–3.20) for women. The excess mortality in both men and women was attributed to cardiovascular, malignant, and infectious diseases. Concomitant diabetes mellitus was observed in 12% of the patients, but only contributed to the increased mortality to a minor extent. Interpretation: Compared with the background population, we observed that the risk ratio for death was more than 2-fold higher in patients with Addison’s disease. Cardiovascular, malignant, and infectious diseases were responsible for the higher mortality rate.

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  • In all these reports, adrenal crisis was a significant cause of death.

    “However, in all these reports, adrenal crisis was a significant cause of death.”

    From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [149]

    The Mortality section reports 36 deaths attributed to adrenal insufficiency but explicitly says that no patient was reported to have died from adrenal crisis under ICD-10. It also cautions that ICD-9 cannot distinguish adrenal crisis from primary adrenal insufficiency, so the study does not establish crisis as a significant cause of death. (LLM, conf=0.87)

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  • Patients with comorbidities, notably asthma and diabetes, are more vulnerable to adrenal crisis.

    “Patients with comorbidities are more vulnerable to adrenal crisis, notably those with asthma and diabetes.”

    From Guidelines for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency (2020) · cites this paper as [19]

    The Discussion reports that patients with both diabetes and primary adrenal insufficiency had a higher risk of death than those with adrenal insufficiency alone. It does not establish a higher risk of adrenal crisis, and the passages found do not identify asthma as a risk factor. The Mortality section says the study could not distinguish adrenal crisis from primary adrenal insufficiency in its ICD-9 records. (LLM, conf=0.82)

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  • Patients with mineralocorticoid or vasopressin dependency are less stable than secondary adrenal patients with intact mineralocorticoid function.

    “Patients with mineralocorticoid or vasopressin dependency are also less stable than secondary adrenal patients with intact mineralocorticoid function [19].”

    From Guidelines for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency (2020) · cites this paper as [19]

    The Discussion (page unavailable) suggests that mineralocorticoid insufficiency may compromise survival in patients with primary adrenal insufficiency. It does not address vasopressin dependency or compare these patients’ stability with that of secondary adrenal patients with intact mineralocorticoid function. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Mortality of patients with PAI was increased in some but not all studies.

    “Mortality of patients with PAI was increased in some (149, 150), but not all studies (7).”

    From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [149]

  • Excess mortality in both men and women with adrenal insufficiency was attributable to cardiovascular, malignant and infectious diseases.

    “Excess mortality in both men and women was attributable to cardiovascular, malignant and infectious diseases [19].”

    From Guidelines for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency (2020) · cites this paper as [19]

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Research works printed but not linked: 1

  1. [11]11. Dunlop D 1963 Eighty-six cases of Addison's disease. Br Med J 5362:887-891

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Authors
Bergthorsdottir, R., Leonsson-Zachrisson, M., Odén, A., & Johannsson, G.
Affiliations
  • Sahlgrenska University Hospital (SE)
  • Department of Endocrinology (R.B., M.L.-Z., G.J.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden
  • Department of Mathematical Sciences (A.O.), Chalmers University of Technology, SE-412 96 Gothenburg, Sweden
Corresponding author
Bergthorsdottir, Ragnhildur
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2006-12-01
Volume
91
Issue
12
Pages
4849-4853
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2006-0076
OpenAlex
W2132382547
Semantic Scholar
6bcbe4e09c391e0932d182ad464f978944049fc9
Cited by
490
References
32
Citations by year
2026: 13 · 2025: 21 · 2024: 27 · 2023: 24 · 2022: 30 · 2021: 28 · 2020: 37 · 2019: 32 · 2018: 23 · 2017: 31 · 2016: 36 · 2015: 23 · 2014: 46 · 2013: 25 · 2012: 19
FWCI
9.06
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Chalmers Publication Library (Chalmers University of Technology) (submittedVersion)
  • Chalmers Research (Chalmers University of Technology) (submittedVersion)
Funders
  • Sahlgrenska Universitetssjukhuset
  • Socialstyrelsen
  • Sahlgrenska Akademin
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords
Addison's disease, premature mortality, all-cause mortality, excess mortality, cardiovascular disease, cancer, infectious diseases, diabetes mellitus, sex differences
MeSH terms
Addison Disease, Adult, Diabetes Mellitus, Female, Humans, Male, Middle Aged, Sweden, Cohort Studies, Comorbidity, Odds Ratio

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