Hypothalamic-Pituitary-Adrenal Axis in Rheumatoid Arthritis

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Does HPA dysfunction predispose to RA?

Adrenal glucocorticoids, secreted in response to pituitary adrenocorticotropic hormone (ACTH) stimulation, are considered among the key factors involved in regulation of immune responses. Thus dysfunction of the HPA axis has been suspected to be involved in the onset or perpetuation of chronic inflammation in RA. It has been suggested that inherited or acquired down-regulation of the HPA axis essentially would create a predisposing environment for autoimmunity development.2

Specific gene

Clinical evidence for HPA dysfunction in RA

In general, clinical studies in RA demonstrate normal HPA function, which has been considered inappropriately normal for the given level of inflammation.10 Although subtle differences in endocrine parameters were detected in the clinical studies in RA, their significance for immune system modulation remains unclear.

Interpretations of the inappropriately normal HPA function in RA range from an innate deficiency in the NEI loop effector component, which would be independent of ongoing

Cortisol kinetics and bioavailability in RA

Evaluation of HPA axis perturbations in RA has been mainly based on an assessment of hormone concentrations in the plasma. An actual concentration of a hormone in plasma depends not only on its secretion but also on the concurrent elimination. As an example, cortisol is metabolized irreversibly by 5-alpha- and 5-beta-reductases to 5-alpha-tetrahydrocortisol and 5-beta-tetrahydrocortisol or converted to biologically inactive cortisone by 11-beta-hydroxysteroid dehydrogenases type 2. Cortisone

Adrenal androgens in RA

Most physiologic attention had previously been given to the tropic (stimulation) aspects in the HPA negative feedback signaling system.30 Little attention has been given to considerations of trophic (cell mass/competence) influences, which may apply, particularly at the adrenal gland level.31 Specifically, adrenal glands of premenopausal-onset RA patients or susceptibles may have relatively deficient mass capacity of their endocrine function, particularly of the zona reticularis production of

Summary

The controlled data accumulated so far support only subtle alterations in HPA axis function in RA, mainly at the adrenal level, and particularly in a subset of premenopausal-onset women. Such interpretation is supported by consistent findings of lower levels of adrenal androgens, particularly DHEAS, in premenopausal-onset RA patients. Consequences of the subtle HPA alterations in RA for the disease development remain unclear. From a broader perspective, the unresponsiveness of the HPA axis to

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    This work was supported by grants VEGA 2/0187/09, RASGENAS N00024, NFM/EEA grant SK0095 and CENDO SAV.

    The authors have nothing to disclose.

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