Robert M. Bennett, M.D.
Oregon Health and Sciences University

Over the last 8 years it has become apparent that a subset of fibromyalgia patients have a dysfunction of their hypothalamic pituitary axis. The research at Oregon Health Sciences University has concentrated on abnormal growth hormone (GH) secretion; other researchers have focused on abnormal cortisol production. It is likely that both of these endocrine abnormalities relate to perturbation of the stress response and its effects on the release of corticotrophin releasing hormone (CRH).

We have found that about one third of FM patients have abnormally low levels of IGF-1 (a stable marker of GH production). Some patients who have initially normal levels of IGF-1, have a precipitous decline in IGF-1 levels over 2-3 years. Standard GH simulation tests with Clonidine and L-Dopa are usually abnormal in FM patients; however, GH stimulation with Arginine is usually normal. As Arginine stimulates GH secretion by inhibiting somatostatin (a GH inhibiting molecule found in the hypothalamus), we reasoned that enhanced somatostatin tone may result in a physiological block to GH secretion in fibromyalgia. By inhibiting somatostatin tone with Pyridostigmine, we were able to normalize GH production in FM patients when they were subjected to strenuous exercise (another stimulus for GH secretion). Thus it appears likely that enhanced hypothalamic somatostatin tone contributes to sub-optimal GH secretion in a subset of FM patients. Somatostatin secretion is stimulated by CRH, thus linking abnormalities of the GH and cortisol response to the stress axis. Importantly GH deficient FM patients benefit from GH replacement therapy. Unfortunately, this is prohibitively expensive (about $1,000/month). Strategies to normalize somatostatin tone may be a more practical approach to cost-effective therapy of GH deficiency in fibromyalgia.

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