OBJECTIVE: 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
PATIENTS AND DESIGN: 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.
RESULTS: 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).
CONCLUSIONS: 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.