OBJECTIVE A number of dynamic tests of the hypothalamic-pituitary-adre
nal axis provide evidence for a mild central adrenal insufficiency in
chronic fatigue syndrome (CFS). The 1 mu g adrenocorticotropin (ACTH)
test has been proposed to be more sensitive than the standard 250 mu g
ACTH test in the detection of subtle pituitary-adrenal hypofunctionin
g. We aimed to establish whether the 1 mu g ACTH test would support su
ch a dysregulation in CFS, and also, given the relative novelty of thi
s test in clinical practice and the uncertainty with regard to appropr
iate cut-off Values for normality, to compare our healthy volunteer da
ta with those of previous studies. PATIENTS AND DESIGN Twenty subjects
with CFS, diagnosed according to Centres for Disease Control and Prev
ention criteria, were compared with 20 healthy volunteer subjects. AII
participants underwent a 1 mu g ACTH test beginning at 1400h. Plasma
samples for cortisol estimation were drawn at 0, +30 and +40 min. RESU
LTS Baseline cortisol values did not differ between CFS patients and h
ealthy 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 significan
t differences. Using an incremental cortisol of > 250 nmol/l as an arb
itrary 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 =
33, P< 0.05). CONCLUSIONS This study provides further evidence for a s
ubtle pituitary-adrenal insuffiency in subjects with chronic fatigue s
yndrome compared to healthy volunteers. Disparities between our health
y volunteer data and those of other groups using the 1 mu g ACTH test
suggest that the test may not be as reliable as previously indicated.