E2 ModeratePreliminaryPEM unclearCross-SectionalPeer-reviewedMachine draft
[Disorder of adrenal gland function in chronic fatigue syndrome].
Zarković, Milos, Pavlović, Milorad, Pokrajac-Simeunović, Ana et al. · Srpski arhiv za celokupno lekarstvo · 2003 · DOI
Quick Summary
This study tested how well the adrenal glands (which produce stress hormones) respond to a small dose of ACTH hormone in people with ME/CFS, compared to healthy people and those with adrenal problems from steroid use. The researchers found that some people with ME/CFS had a slower initial hormone response similar to adrenal insufficiency, but the response eventually caught up. This suggests ME/CFS patients may have a subtle problem with how quickly their adrenal glands respond to signals.
Why It Matters
This research addresses a longstanding question about whether ME/CFS involves abnormalities in the hormonal stress-response system, which could explain fatigue and other symptoms. Finding that some ME/CFS patients have reduced early adrenal responsiveness, even if not universally present, supports a biological basis for the illness and could guide future treatment research.
Observed Findings
- Cortisol concentration at 15 and 30 minutes post-ACTH was significantly lower in CFS versus healthy controls, but similar to secondary adrenal insufficiency.
- Cortisol increment (change from baseline) at 15 and 30 minutes was significantly higher in healthy controls than in both CFS and adrenal insufficiency groups.
- Maximal cortisol response, maximal cortisol increment, and area under the curve showed no significant difference between CFS and healthy controls.
- The CFS group demonstrated heterogeneous responses, with some subjects showing preserved responses and others resembling adrenal insufficiency.
Inferred Conclusions
- ME/CFS involves reduced adrenal responsiveness to ACTH, particularly evident in the early phase (15–30 minutes) of stimulation.
- ME/CFS patients represent a heterogeneous population with respect to adrenal function; not all show the same degree of impairment.
- Previous conflicting results in the literature likely reflect both methodological differences and true heterogeneity within the ME/CFS population.
Remaining Questions
- What proportion of the ME/CFS population has clinically significant adrenal impairment, and does this correlate with symptom severity or other disease markers?
- Is the reduced early adrenal responsiveness a primary pathophysiological feature or a consequence of chronic illness?
What This Study Does Not Prove
This study does not prove that adrenal dysfunction causes ME/CFS, nor does it establish that all ME/CFS patients have the same degree of adrenal impairment. The cross-sectional design cannot determine if adrenal changes precede symptom onset or result from the illness. Small sample size (n=9) limits generalizability.
Tags
Symptom:Fatigue
Biomarker:Blood Biomarker
Method Flag:Weak Case DefinitionSmall SampleExploratory Only
Metadata
- DOI
- 10.2298/sarh0310370z
- PMID
- 15058215
- Review status
- Machine draft
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 8 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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