Does Low Cortisol Cause Fibromyalgia?
Low cortisol levels do not cause fibromyalgia, but fibromyalgia is associated with mild hypocortisolism and HPA axis dysregulation as a consequence of the syndrome, not as its cause. 1, 2
Understanding the Relationship Between Cortisol and Fibromyalgia
Fibromyalgia is the Primary Disorder
Fibromyalgia is recognized as a complex condition characterized by abnormal pain processing and secondary features, not as a manifestation of adrenal insufficiency. 3
The EULAR guidelines for fibromyalgia management make no mention of treating underlying cortisol deficiency, instead focusing on pain management, exercise, and psychological interventions as primary treatments. 3
Symptoms attributed to fibromyalgia (pain, fatigue) are very unspecific and could be related to multiple concomitant pathologies including hypothyroidism, hypocortisolism, vitamin deficiencies, depression, and neoplasia—but no solid etiopathogenic autoimmune link has been confirmed between fibromyalgia and these conditions. 3
The Cortisol Abnormalities Found in Fibromyalgia
Research demonstrates that fibromyalgia patients exhibit mild hypocortisolism with HPA axis dysregulation, but this represents a consequence rather than a cause:
Fibromyalgia patients display significantly lower 24-hour urinary free cortisol levels and lower basal total plasma cortisol compared to controls, but this is accompanied by hyperreactive pituitary ACTH release to CRH stimulation. 1
The pattern shows glucocorticoid feedback resistance with reduced containment of the stress-response system by corticosteroid hormones, suggesting the HPA axis dysfunction is secondary to the fibromyalgia syndrome itself. 1
Fibromyalgia patients have basal hypocortisolism but no cortisol hypersuppression after dexamethasone administration, distinguishing them from primary adrenal disorders and trauma-related syndromes. 4
Critical Distinction: Fibromyalgia vs. True Adrenal Insufficiency
The cortisol levels in fibromyalgia are fundamentally different from pathologic adrenal insufficiency:
True secondary adrenal insufficiency requires peak cortisol <500 nmol/L (<18 μg/dL) on ACTH stimulation testing, with clinical features of hypotension, collapse, and electrolyte abnormalities. 5
A subset of fibromyalgia patients (22 patients in one study) demonstrated concurrent secondary adrenal insufficiency on insulin tolerance testing (peak cortisol 5.4-17 mcg/dL), but 79% had normal cosyntropin stimulation tests, indicating the ITT findings may represent altered stress response rather than true adrenal failure. 6
When true adrenal insufficiency coexists with fibromyalgia symptoms, it represents a separate comorbid condition requiring specific diagnostic confirmation, not a causal relationship. 6
The Pathophysiology Points Away from Causation
The evidence indicates disturbed glucocorticoid receptor function rather than simple cortisol deficiency:
Fibromyalgia patients exhibit reduced glucocorticoid sensitivity of inflammatory cytokine production despite normal cortisol awakening response and daytime cortisol profiles. 2
Pressure pain threshold testing induces three times higher cortisol levels and four times higher IL-6 levels in fibromyalgia patients, with enhanced IL-6 reactivity correlating with increased pain and fatigue severity. 2
This suggests the pathophysiologic relevance lies in disturbed glucocorticoid receptor function maintaining fibromyalgia symptoms, not in absolute cortisol deficiency causing the syndrome. 2
Clinical Implications and Pitfalls
When to Consider Adrenal Testing
Hypocortisolism should be ruled out as a separate diagnosis when fibromyalgia symptoms are present, but not assumed to be the cause:
Adrenal insufficiency must be definitively excluded before attributing symptoms solely to fibromyalgia, particularly when patients have unexplained hypotension, collapse, or electrolyte abnormalities. 5
Morning cortisol and ACTH measurements followed by ACTH stimulation testing (if initial results are indeterminate) are appropriate to rule out true adrenal insufficiency. 5
Cosyntropin stimulation testing should not be used to exclude secondary adrenal insufficiency in fibromyalgia patients, as it may be falsely normal even when ITT is abnormal. 6
Treatment Approach
Optimal fibromyalgia treatment requires multidisciplinary management without assuming cortisol replacement will resolve symptoms:
Heated pool exercise, individually tailored aerobic and strength training programs, and cognitive behavioral therapy are evidence-based non-pharmacological treatments. 3
Pharmacological management includes tramadol for pain, antidepressants (amitriptyline, duloxetine, milnacipran), and pregabalin—not corticosteroid replacement. 3
Of 13 fibromyalgia patients with documented secondary adrenal insufficiency who received glucocorticoid replacement, only 62% reported symptom improvement, indicating cortisol replacement does not universally resolve fibromyalgia symptoms even when deficiency is present. 6
Common Pitfall to Avoid
Do not initiate empiric glucocorticoid replacement for fibromyalgia symptoms without documented adrenal insufficiency:
The mild hypocortisolism in fibromyalgia represents HPA axis dysregulation with glucocorticoid resistance, not true deficiency requiring replacement. 1, 2
Exogenous steroids can suppress the HPA axis and confound future diagnostic testing while potentially causing iatrogenic complications. 5
If true adrenal insufficiency is confirmed on appropriate testing, glucocorticoid replacement is indicated for the adrenal disorder, but fibromyalgia symptoms may persist and require separate management. 6