Diagnosis and Treatment of Hypothalamic-Pituitary-Adrenal (HPA) Axis
Dysfunction in Patients with Chronic Fatigue Syndrome (CFS) and
Fibromyalgia (FM)
Journal: J of Chronic Fatigue Syndrome, Vol. 14, No. 3, 2007, pp. 59-88
Author: Kent Holtorf MD
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.
Dysfunction in Patients with Chronic Fatigue Syndrome (CFS) and
Fibromyalgia (FM)
Journal: J of Chronic Fatigue Syndrome, Vol. 14, No. 3, 2007, pp. 59-88
Author: Kent Holtorf MD
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.
