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Published on: September 15, 2017
Adrenal gland dysfunction in males with cluster headache.
Connar Stanley James Westgate1,2,3, Tanja Lylloff4,5, David Møbjerg Kristensen6,7,8
1Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, University of Copenhagen, Glostrup, Denmark. connar.stanley.james.westgate@regionh.dk.
The Journal of Headache and Pain
|May 14, 2026
Summary
Cluster headache is linked to distinct adrenal steroid profiles. Episodic cluster headache shows reduced adrenal synthesis, while chronic forms exhibit stress-induced androgen suppression, suggesting different neurobiological underpinnings.
Area of Science:
- Endocrinology
- Neurology
- Metabolomics
Background:
- Cluster headache is linked to hypogonadism and impaired testicular steroidogenesis.
- Adrenal steroidogenesis dysregulation in cluster headache pathophysiology remains unclear.
- Differences between episodic and chronic cluster headache steroid profiles are unknown.
Purpose of the Study:
- Define the adrenal steroid profile in cluster headache patients.
- Differentiate steroid profiles between episodic cluster headache phases (in bout vs. remission).
- Assess if steroid profiles can distinguish between chronic and episodic cluster headache.
Main Methods:
- Prospective case-control study of adult males: chronic cluster headache (n=60), episodic cluster headache in/out of bout (n=60), and healthy controls (n=60).
- Serum steroid profile analysis of 16 hormones (mineralocorticoids, glucocorticoids, androgens) using liquid chromatography tandem mass-spectrometry.
- Machine learning applied to differentiate cluster headache states based on steroid profiles.
Main Results:
- Episodic cluster headache showed lower mineralocorticoids (11-deoxycorticosterone, corticosterone, aldosterone) versus controls.
- During episodic bouts, lower glucocorticoids (11-deoxycortisol, cortisol) and cortisol/DHEAS ratio were observed compared to remission.
- Chronic cluster headache featured lower 17-OH pregnenolone and DHEAS, with a higher cortisol/DHEAS ratio.
- Steroid profiles distinguished chronic from episodic cluster headache (AUC 0.92).
- Attack frequency correlated with steroid dysfunction in episodic, but not chronic, cluster headache.
Conclusions:
- Distinct adrenal steroid hormone profiles characterize episodic and chronic cluster headache.
- Episodic cluster headache is associated with reduced adrenal steroid synthesis during attacks.
- Chronic cluster headache is linked to stress-induced androgen suppression.
- These steroid profile differences may indicate distinct neurobiological mechanisms for each cluster headache type.
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