Patients with CFS demonstrated subtle alterations in HPA axis activity characterized by reduced ACTH over a full circadian cycle and reduced levels during the usual morning physiological peak ACTH secretion. This provides further evidence of subtle dysregulation of the HPA axis in CFS. Whether this dysregulation is a primary feature of the illness or instead represents a biologic effect secondary to having the illness itself remains unclear.

There were no significant differences in baseline cortisol or cortisol responses between patients and controls. However, responses generally were low, and many subjects' peak responses were prior to the standard 30 minute sampling time., CONCLUSIONS These results do not lend support to the theory that patients with chronic fatigue syndrome have a low adrenal reserve. However, results from studies assessing the HPA axis are proving to be inconsistent. We suggest that many other factors may be contributing to HPA axis alterations in chronic fatigue syndrome, including sleep disturbance, inactivity, altered circadian rhythmicity, illness chronicity, concomitant medication and comorbid psychiatric disturbance. These sources of heterogeneity need to be considered in future studies, and may explain the inconsistent findings to date.

Therapeutic drug monitoring of tricyclic antidepressants is a controversial issue. A case is reported in which a patient with recurrent depression developed asymptomatic tricyclic toxicity while on trimipramine, a tricyclic antidepressant, and diltiazem, a calcium channel blocker. A metabolic interaction involving cytochrome P450 3A (CYP3A) is postulated. It is suggested that routine therapeutic drug monitoring of tricyclic levels should be an essential part of the management of depression.