The low dose ACTH test in Chronic Fatigue Syndrome (CFS) & in health

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

previous studies.

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.

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