Leslie Crofford, M.D.
University of Michigan

We have proposed that FM could be called a stress-related syndrome because symptoms often have their onset triggered by stress (psychological, infectious, traumatic), the clinical observation of increase in symptoms associated with physical or emotional stress, and the finding of high levels of self-reported daily stress. Other conditions that share substantial symptomatic overlap with FM (chronic fatigue syndrome or CFS, irritable bowel syndrome, chronic headache syndromes, dysmenorrhea, and temporomandibular joint disorders) are also thought to be associated with stress.

Stress response systems function to re-establish a steady state after a disturbance. Proper activity of stress response systems at rest and during superimposed stress is crucial for normal daily function and coping. The hypothalamic-pituitary-adrenal (HPA) axis is generally considered to play a pivotal role in the coordinated physiological response to physical and emotional stress.

Our initial finding in FM was normal or increased adrenal glucocorticoid secretion detected by sampling plasma for ACTH and cortisol in the morning and evening, but low 24-h urine free cortisol levels. We also described differences in stimulated activity of the axis characterized by an exaggerated pituitary response to challenge testing in FM.

We have extended our studies to define further the basal circadian pattern of ACTH and cortisol secretion in patients with FM and CFS. We measured plasma ACTH and cortisol determined at 10-minute intervals over a 24-h period, and determined area under the curve, pulsatility, and circadian rhythm. There are significant differences between patient and control groups in the pattern of circadian secretion of ACTH and cortisol. However, cortisol secretion is not out of phase with another prominently circadian hormone, melatonin.

Because the HPA axis has important reciprocal interactions with the gonadal or sex-steroid hormone axes, we used these same samples to evaluate the integrity of the hypothalamic-pituitary-gonadal (HPG) axis in a sub-group of pre-menopausal women with FM and CFS. We found no abnormalities in the central or peripheral components of the axis. The HPA axis has important interactions with other central nervous system functions, including modulation of pain perception, mood, and cognitive function. Our ongoing research seeks to define relationship between HPA axis function and these important symptoms of FM.

Presented at the National Fibromyalgia Research Association's Subgroups in Fibromyalgia Symposium, September 26-27, 1999, in Portland, Oregon.