The low dose ACTH test in chronic fatigue syndrome and in health

A number of dynamic tests of the hypothalamic-pituitary-adrenal axis provide evidence for a mild central adrenal insufficiency in chronic fatigue syndrome (CFS). The 1 microgram adrenocorticotropin (ACTH) test has been proposed to be more sensitive than the standard 250 micrograms ACTH test in the detection of subtle pituitary-adrenal hypofunctioning. We aimed to establish whether the 1 microgram ACTH test would support such a dysregulation in CFS, and also, given the relative novelty of this test in clinical practice and the uncertainty with regard to appropriate cut-off values for normality, to compare our healthy volunteer data with those of previous studies.

Twenty subjects with CFS, diagnosed according to Centres for Disease Control and Prevention criteria, were compared with 20 healthy volunteer subjects. All participants underwent a 1 microgram ACTH test beginning at 1400 h. Plasma samples for cortisol estimation were drawn at 0, +30 and +40 min.

Baseline cortisol values did not differ between CFS patients and healthy subjects. The delta cortisol (maximum increment from baseline) value was significantly lower in the CFS than the volunteer group (P < 0.05). Comparison of the +30 min cortisol values revealed no significant differences. Using an incremental cortisol of > 250 nmol/l as an arbitrary cutoff point, two (10%) of the healthy subjects and nine (45%) of the CFS subjects failed the test on this basis (chi 2 = 4.3, df = 38, P < 0.05).

This study provides further evidence for a subtle pituitary-adrenal insufficiency in subjects with chronic fatigue syndrome compared to healthy volunteers. Disparities between our healthy volunteer data and those of other groups using the 1 microgram ACTH test suggest that the test may not be as reliable as previously indicated.