Diag. & Treatment of Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysfunction in CFS,FM patients
JOURNAL OF CHRONIC FATIGUE SYNDROME VOLUME 14:3 (pub) 2008
Diagnosis and Treatment of Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysfunctionin Patients with Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM)
Kent Holtorf M.D.
Medical Director, Holtorf Medical Group, Inc. Torrance, CA
There is controversy regarding the incidence and significance of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in chronic fatigue syndrome (CFS) and fibromyalgia (FM). Studies that utilize central acting stimulation tests, including corticotropin-releasing hormone (CRH), insulin stress testing (IST), d-fenfluramine, ipsapirone, interleukin-6 (IL-6) and metyrapone testing, have demonstrated that HPA axis dysfunction of central origin is present in a majority of these patients. However, ACTH stimulation tests and baseline cortisol testing lack the sensitivity to detect this central dysfunction and have resulted in controversy and confusion regarding the incidence of HPA axis dysfunction in these conditions and the appropriateness of treatment. While both CFS and FM patients are shown to have central HPA dysfunction, the dysfunction in CFS is at the pituitary-hypothalamic level while the dysfunction in FM is more related to dysfunction at the hypothalamic and supra-hypothalamic levels. Because treatment with low physiologic doses of cortisol (<15 mg) has been shown to be safe and effective and routine dynamic ACTH testing does not have adequate diagnostic sensitivity, it is reasonable to give a therapeutic trial of physiologic doses of cortisol to the majority of patients with CFS and FM, especially to those who have symptoms that are consistent with adrenal dysfunction, have low blood pressure or have baseline cortisol levels in the low or low-normal range.
Key words: HPA axis dysfunction; hypothalamic-pituitary-adrenal axis; chronic fatigue syndrome; fibromyalgia; CFIDS; cortisol, hydrocortisone
Chronic Fatigue Syndrome (CFS) and fibromyalgia (FM) are disabling conditions that are shown to be present in 0.5-5% of the population and often coexist (1-3). Treating CFS and FM patients is often frustrating for physicians as there is no clear etiology or treatment, and the use of standard recommended treatments that dont address the underlying pathophysiology, including NSAIDS, antidepressants and muscle relaxants, are largely ineffective and have significant side-effects (4-7). Reliance on these medications results in a poor prognosis and is unsatisfying for both patients and physicians (8-18). There is unlikely a single causative agent or process occurring in these conditions. The hypothalamic-pituitary dysfunction that is present in the majority of CFS and FM patients results in HPA axis dysfunction that is often not detected by standard testing done in a clinical setting, as these tests are designed to detect primary adrenal insufficiency and have poor sensitivity for secondary or tertiary adrenal insufficiency (19-58). In addition, this hypothalamic-pituitary dysfunction results in secondary and/or tertiary hypothyroidism (as well as evidence of thyroid resistance) that is not detected with standard thyroid testing (27,59-69), and low growth hormone production that is also not detected by standard testing (27,60,70-74). There has also been shown to be associated mitochondrial dysfunction (75-78), sleep disorder (79-84), immune dysfunction (85-95), chronic infections (96-105), autonomic dysfunction (106-108), gastrointestinal dysfunction (109-113) and coagulation dysfunction (114-119) in these patients.