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Cited by 77Adrenal Hormones and DisordersHormonal Regulation and HypertensionHormonal and reproductive studies

Increased mortality risk in patients with primary and secondary adrenal insufficiency

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Ngaosuwan, Kanchana, Johnston, Desmond G, Godsland, Ian F, Cox, Jeremy, Majeed, Azeem, Quint, Jennifer K, Oliver, Nick, Robinson, Stephen·2021·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/clinem/dgab096
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Abstract

Context: Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations. Objective: To compare mortality risk and causes of death in adrenal insufficiency with an individually matched reference population. Methods: A retrospective cohort study was done using a UK general practitioner database (CPRD). A total of 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) were compared with 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcomes were all-cause and cause-specific mortality, and hospital admission from adrenal crisis. Results: With follow-up of 40 799 and 406 899 person-years for patients and controls respectively, the hazard ratio (HR [95% CI]) for all-cause mortality was 1.68 [1.58-1.77]. HRs were greater in primary (1.83 [1.66-2.02]) than in secondary (1.52 [1.40-1.64]) disease; primary versus secondary disease (1.16 [1.03-1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15-7.46]). Adrenal crisis contributed to 10% of all deaths. In the first 2 years following diagnosis, the patients’ mortality rate and hospitalization from adrenal crisis were higher than in later years. Conclusion: Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality.

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Crossref · 10.1210/clinem/dgab096

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  • One published cohort study in the UK from 1987 to 2017 showed a significant rise in mortality rates in patients with adrenal insufficiency compared to matched healthy controls, and the risk is significantly higher in patients with primary adrenal insufficiency compared to secondary adrenal insufficiency.

    “One published cohort study in the UK from 1987 to 2017 showed a significant rise in mortality rates in patients with AI compared to matched healthy controls, and the risk is significantly higher in patients with PAI compared to SAI.”

    From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [43]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • Adrenal crisis was found to be an associated cause of death in 10% of those with adrenal insufficiency, mainly due to a compromise in the circulatory system.

    “Adrenal crisis was found to be an associated cause of death in 10% of those with adrenal insufficiency, and this was mainly due to a compromise in the circulatory system.”

    From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [43]

  • Mortality rates in patients with adrenal insufficiency and accompanying diabetes were higher than those with adrenal insufficiency alone.

    “Although it was difficult to ascertain if hypoglycaemia partly contributed to the adrenal crisis-associated deaths, it was identified that mortality rates in patients with AI and accompanying diabetes were higher than those with AI alone (43).”

    From Hypoglycaemia in adrenal insufficiency (2023) · cites this paper as [43]

  • Adrenal insufficiency is a cause of hypoglycemia.

    “Adrenal insufficiency (AI) is another cause of hypoglycemia.”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [30]

    The All-cause Mortality and diabetes-stratified mortality sections examine death rates in patients with adrenal insufficiency, not hypoglycemia. Searches for “hypoglycemia” and “low blood glucose” found no passage in our copy stating that adrenal insufficiency causes hypoglycemia. (LLM, conf=0.75)

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  • The incidence of AI-related hypoglycemia is not well characterized, although the risk appears to be higher in primary compared to secondary AI.

    “However, the incidence of AI-related hypoglycemia is not well characterized, although the risk appears to be higher in primary compared to secondary AI [30].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [30]

    The Role of Adrenal Crisis in Increased Mortality section reports higher adrenal-crisis admission rates in primary than secondary adrenal insufficiency, but adrenal crisis is not the claimed outcome of hypoglycemia. A search of our copy for hypoglycemia found no passage characterizing its incidence or comparing its risk between the two groups. (LLM, conf=0.76)

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Authors
Ngaosuwan, K., Johnston, D. G., Godsland, I. F., Cox, J., Majeed, A., Quint, J. K., Oliver, N., & Robinson, S.
Affiliations
  • Chulabhorn Royal Academy (TH)
  • Imperial College London (GB)
  • St Mary's Hospital (GB)
Corresponding author
Ngaosuwan, Kanchana
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2021-02-17
Volume
106
Issue
7
Pages
e2759-e2768
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/clinem/dgab096
OpenAlex
W3132009980
Cited by
77
References
29
Citations by year
2026: 9 · 2025: 14 · 2024: 16 · 2023: 13 · 2022: 17 · 2021: 8
FWCI
10.08
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Spiral (Imperial College London) (submittedVersion)
Funders
National Institute for Health and Care Research
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
adrenal insufficiency, Addison's disease, secondary adrenal insufficiency, mortality risk, causes of death, cardiovascular disease, infection-related mortality, adrenal crisis, hospitalization, clinical course
MeSH terms
Acute Disease, Adrenal Insufficiency, Adult, Aged, Cardiovascular Diseases, Cause of Death, Female, United Kingdom, Hospitalization, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Databases, Factual, General Practice

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