Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (823 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An adrenal disease characterized by the progressive destruction of the adrenal cortex, resulting in insufficient production of aldosterone and hydrocortisone. Clinical symptoms include anorexia; nausea; weight loss; muscle weakness; and hyperpigmentation of the SKIN due to increase in circulating levels of ACTH precursor hormone which stimulates melanocytes.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Disease, Addison; Addison's Disease; Addisons Disease; Primary Adrenal Insufficiency; Adrenal Insufficiency, Primary; Primary Adrenocortical Insufficiency; Adrenocortical Insufficiencies, Primary; Adrenocortical Insufficiency, Primary.
Where it fits in the MeSH classification
- Broader topics
- Adrenal Insufficiency; Autoimmune Diseases
- Narrower topics
- Hypoadrenocorticism, Familial
Related concepts
- Adrenal Cortex
- Aldosterone
- Hydrocortisone
- Anorexia
- Nausea
- Weight Loss
- Muscle Weakness
- Hyperpigmentation
- Melanocytes
Research landscape
PubMed indexes 5,061 records tagged with the MeSH heading “Addison Disease” (counts retrieved 2026-10-29). 376 of them (7.4%) were published from 2020 onward, and the busiest period so far is through 1999 with 3,453 records.
Reviews account for 498 records (9.8%) and meta-analyses for 9. Randomized controlled trials number 37 (0.7%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 3,453 |
| 2000-2009 | 571 |
| 2010-2019 | 661 |
| 2020 onward | 376 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 498 | 9.8% |
| Meta-analyses | 9 | 0.2% |
| Randomized controlled trials | 37 | 0.7% |
Method: PubMed query "Addison Disease"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in immunology
Immune responses are studied in model organisms, in cells from donors and in patients, and the same pathway can behave differently across these settings. Mouse immune systems differ from human ones in important ways, and blood measurements may not reflect what happens in tissues. Clinical conclusions about immune-mediated disease or immunotherapy come mainly from controlled trials and long-term cohorts. Check the species and tissue studied, whether markers were linked to outcomes patients notice, and the follow-up time.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality | 2017 | Research article Design not recorded in structured metadata | 91 | cc by PMID 28223394 · DOI · PMC5425935 |
| Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe | 2013 | Review article Design not recorded in structured metadata | 79 | cc by PMID 24031090 · DOI · PMC3805018 |
| Primary adrenal insufficiency: New genetic causes and their long-term consequences | 2020 | Review article Design not recorded in structured metadata | 63 | cc by PMID 31610036 · DOI · PMC6916405 |
| Addison's disease in Italy: mortality and survival by etiology | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 42171676 · DOI · PMC13486020 |
Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality [1]
Abstract reading summary — source excerpts
- Opening excerpt
- ObjectiveMortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death.
- Closing excerpt
- This potential impairment in anti-viral immune defense may contribute to the increased rate of respiratory infections and ultimately mortality in PAI.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (215 words)
ObjectiveMortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection.Design and methodsWe undertook a cross-sectional study of 42 patients with PAI due to autoimmune adrenalitis (n = 37) or bilateral adrenalectomy (n = 5) and 58 sex- and age-matched controls. A comprehensive screen of innate immune function, consisting of measurements of neutrophil phagocytosis, reactive oxygen species production, NK cell cytotoxicity (NKCC) and NK cell surface receptor expression, was performed on all subjects.ResultsNeutrophil function did not differ between PAI and controls. However, NKCC was significantly reduced in PAI (12.0 ± 1.5% vs 21.1 ± 2.6%, P P P ConclusionsAdrenal insufficiency is associated with significantly decreased NKCC, thereby potentially compromising early recognition and elimination of virally infected cells. This potential impairment in anti-viral immune defense may contribute to the increased rate of respiratory infections and ultimately mortality in PAI.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28223394 · DOI · PMC5425935
Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundConventional glucocorticoid (GC) replacement for patients with adrenal insufficiency (AI) is inadequate.
- Closing excerpt
- New preparations are being developed to better mimic normal physiological cortisol levels with convenient, once-daily dosing which may improve treatment outcomes.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (223 words)
BackgroundConventional glucocorticoid (GC) replacement for patients with adrenal insufficiency (AI) is inadequate. Patients with AI continue to have increased mortality and morbidity and compromised quality of life despite treatment and monitoring.Objectivesi) To review current management of AI and the unmet medical need based on literature and treatment experience and ii) to offer practical advice for managing AI in specific clinical situations.MethodsThe review considers the most urgent questions endocrinologists face in managing AI and presents generalised patient cases with suggested strategies for treatment.ResultsOptimisation and individualisation of GC replacement remain a challenge because available therapies do not mimic physiological cortisol patterns. While increased mortality and morbidity appear related to inadequate GC replacement, there are no objective measures to guide dose selection and optimisation. Physicians must rely on experience to recognise the clinical signs, which are not unique to AI, of inadequate treatment. The increased demand for corticosteroids during periods of stress can result in a life-threatening adrenal crisis (AC) in a patient with AI. Education is paramount for patients and their caregivers to anticipate, recognise and provide proper early treatment to prevent or reduce the occurrence of ACs.ConclusionsThis review highlights and offers suggestions to address the challenges endocrinologists encounter in treating patients with AI. New preparations are being developed to better mimic normal physiological cortisol levels with convenient, once-daily dosing which may improve treatment outcomes.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 24031090 · DOI · PMC3805018
Primary adrenal insufficiency: New genetic causes and their long-term consequences [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that requires urgent diagnosis and treatment.
- Closing excerpt
- In some situations, milder or nonclassic forms of these conditions can first present in adulthood and may have been labelled, "Addison's disease."
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (206 words)
Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that requires urgent diagnosis and treatment. Whilst the most common causes are congenital adrenal hyperplasia (CAH) in childhood and autoimmune adrenal insufficiency in adolescence and adulthood, more than 30 other physical and genetics cause of PAI have been reported. Reaching a specific diagnosis can have implications for management and for monitoring associated features, as well as for counselling families about recurrence risk in siblings and relatives. Here, we describe some recent insights into the genetics of adrenal insufficiency and associated molecular mechanisms. We discuss (a) the role of the nuclear receptors DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human adrenal and reproductive dysfunction; (b) multisystem growth restriction syndromes due to gain-of-function in the growth repressors CDKN1C (IMAGE syndrome) and SAMD9 (MIRAGE syndrome), or loss of POLE1; (c) nonclassic forms of STAR and P450scc/CYP11A1 insufficiency that present with a delayed-onset adrenal phenotype and represent a surprisingly prevalent cause of undiagnosed PAI; and (d) a new sphingolipidosis causing PAI due to defects in sphingosine-1-phosphate lyase-1 (SGPL1). Reaching a specific diagnosis can have life-long implications for management. In some situations, milder or nonclassic forms of these conditions can first present in adulthood and may have been labelled, "Addison's disease."
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31610036 · DOI · PMC6916405
Addison's disease in Italy: mortality and survival by etiology [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundData on survival and mortality in Addison's disease (AD) are contradictory: some studies suggest a mortality rate two times higher than in the general population, but this is not consistently reported in other studies.
- Closing excerpt
- In order to evaluate survival and mortality each form of AD must be considered separately and compared with an age- and sex-matched population.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (179 words)
BackgroundData on survival and mortality in Addison's disease (AD) are contradictory: some studies suggest a mortality rate two times higher than in the general population, but this is not consistently reported in other studies.MethodsWe evaluated survival and mortality in 1,826 Italian adult patients with AD of different etiologies, collected from 1947 to 2024 across 30 Endocrine Units. These outcomes were compared to those of the age- and sex-matched Italian reference population using a standardized mortality ratio (SMR) in a subgroup of 1,575 cases.ResultsSex and age adjusted survival analysis showed increased mortality in genetic AD, cancer-related-AD and cases with type 1 autoimmune polyendocrine syndrome (APS-1) compared to other etiologies. The SMR analysis demonstrated a significantly increased mortality risk of the overall patients with AD compared to the general population (SMR 1.34, p ConclusionOur study has shown that in adult patients with AD there is a large difference in survival and mortality based on the various etiological forms. In order to evaluate survival and mortality each form of AD must be considered separately and compared with an age- and sex-matched population.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42171676 · DOI · PMC13486020
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints [5]
- Research article A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors [6]
- Research article Two types of autoimmune Addison's disease associated with different polyglandular autoimmune (PGA) syndromes [7]
- Research article Measuring cortisol in serum, urine and saliva - are our assays good enough? [8]
- Research article Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency [9]
- Research article Clinical review 130: Addison's disease 2001 [10]
References
- Bancos I, Hazeldine J, Chortis V, Hampson P, Taylor AE, Lord JM, et al.. Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality. . 2017. PMID 28223394 · DOI · PMC5425935
- Grossman A, Johannsson G, Quinkler M, Zelissen P. Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe. . 2013. PMID 24031090 · DOI · PMC3805018
- Buonocore F, Achermann JC. Primary adrenal insufficiency: New genetic causes and their long-term consequences. . 2020. PMID 31610036 · DOI · PMC6916405
- Vedolin CK, Sabbadin C, Mondin A, Masiero S, Barbot M, Cavedon E, et al.. Addison's disease in Italy: mortality and survival by etiology. . 2026. PMID 42171676 · DOI · PMC13486020
- Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2019. PMID 30184160 · DOI · PMC6270990
- de Filette J, Andreescu CE, Cools F, Bravenboer B, Velkeniers B. A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors. Horm Metab Res. 2019. PMID 30861560 · DOI
- Neufeld M, Maclaren NK, Blizzard RM. Two types of autoimmune Addison's disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine (Baltimore). 1981. PMID 7024719 · DOI
- El-Farhan N, Rees DA, Evans C. Measuring cortisol in serum, urine and saliva - are our assays good enough?. Ann Clin Biochem. 2017. PMID 28068807 · DOI
- Husebye ES, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, et al.. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med. 2014. PMID 24330030 · DOI
- Ten S, New M, Maclaren N. Clinical review 130: Addison's disease 2001. J Clin Endocrinol Metab. 2001. PMID 11443143 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.