The Hypothalamic-Pituitary-Adrenal Stress Axis in the Fibromyalgia Syndrome

Objectives: The hypothalamic-pituitary-adrenal [HPA] axis is a neuroendocrine stress-response system. Stress can be defined as a disturbance [metabolic, physiologic, traumatic, inflammatory/infectious, or psychoemotional] that perturbs homeostasis and leads to activation of stereotypical stress-adaptation mechanisms, including the HPA axis and the sympathetic nervous system. Patients with the fibromyalgia [FM] syndrome often report the onset of symptoms following an acute stress or a period of intense stress. In addition, symptoms are commonly exacerbated during periods of stress, and patients report increased levels of daily stress. Patients with FM have been found to have perturbed HPA axis function. The sympathetic stress response system may also be dysfunctional in FM patients. Since the HPA axis is interconnected with other neuroendocrine systems, the HPA axis will be discussed in the context of other neurohormonal abnormalities found in patients with FM. Results: Patients with FM exhibit a unique pattern of HPA axis perturbation characterized by exaggerated adrenocorticotropic hormone [ACTH] response to exogenous corticotropin-releasing hormone [CRH] or to endogenous activators of CRH such as insulin-induced-hypoglycemia. The cortisol response to increased ACTH is blunted. Integrated basal cortisol levels measured by 24-hour urine-free cortisol are low, and there is blunting of the circadian rhythm of plasma cortisol. Plasma neuropeptide Y [NPY], a peptide co-localized with norepinephrine in the sympathetic nervous system, is low in patients with FM. Conclusions: There are disturbances in the function of the HPA and sympathetic stress-response systems in FM that may play a role in the pathophysiology of this syndrome.