Adults with autoimmune primary adrenal insufficiency, also called autoimmune Addison’s disease, report poorer health-related quality of life than healthy people or population reference groups, particularly in vitality, energy and their general view of health, a systematic review has found. Six comparative studies consistently reported this pattern.
The review did not produce a single pooled score. The studies used different designs, questionnaires and analytical approaches, so the findings were synthesized across studies rather than combined in a meta-analysis.
A broad but varied evidence base
The review asked what quantitative research shows about quality of life and psychological outcomes in adults with autoimmune primary adrenal insufficiency. It included English-language, peer-reviewed full-text studies of adults aged 18 or older with confirmed autoimmune disease. Mixed Addison’s disease cohorts were eligible when autoimmune results were reported separately or when at least 90% of the sample had autoimmune primary adrenal insufficiency.
The researchers followed PRISMA 2020 and searched PubMed, Scopus and Web of Science from inception through February 2026. Study selection and data extraction were done independently twice, with a third reviewer consulted when disagreements remained. Study quality was assessed with NIH Study Quality Assessment Tools.
The final synthesis covered 23 studies and 1,764 participants with explicitly reported autoimmune primary adrenal insufficiency. The evidence included eight cross-sectional studies, five case-control studies, nine interventional trials and one prospective observational study.
Quality appraisal classified 22 studies as fair and one controlled intervention study as good; none was rated poor.
Energy and vitality stood out
Across the comparative evidence, lower quality of life was most consistently visible in vitality, energy and general health perception. The review describes a pattern across groups, not a prediction of how any one person will feel.
Female sex and greater autoimmune comorbidity were repeatedly associated with poorer reported outcomes. Those findings do not establish that either factor caused the differences, and they do not show that autoimmune primary adrenal insufficiency alone accounts for every problem reported in the studies.
The review also considered psychological outcomes, but differences in how those outcomes were measured made them harder to compare than the recurring findings on energy, vitality and general health.
Treatment comparisons did not settle the question
Treatment findings were mixed. Several studies found no significant differences between the groups being compared, while modified-release hydrocortisone and continuous subcutaneous infusion were more consistently associated with improvements in disease-specific quality of life.
Changes in generic quality of life and sleep were less consistent. The findings therefore do not establish that either treatment strategy is superior for all patients.
What the review can and cannot answer
Most of the evidence was observational, and the studies differed in their outcomes, instruments and analytical approaches. That limits what can be concluded about cause and effect.
Taken together, the review identifies a consistent patient-reported burden in comparative studies, especially around vitality, energy and general health, but leaves the size of that burden and the best long-term replacement approach unresolved. Future studies will need more consistent measures and stronger longitudinal and randomized comparisons to answer those questions.
Paper data and sources
Original title: Health-related quality of life and patterns of psychological vulnerability in autoimmune Addison’s disease: a systematic review
Authors: Silvestro O, Costa L, Ferraù F et al.
Journal/Repository: Frontiers in endocrinology
Status: Peer-reviewed
First online: 2026-10-09
DOI: Not available
Original paper · Full text