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Andre Barkhuizen, Stephen M. Campbell,
Robert M. Bennett, M. Samuels, Peter S. Spencer,
Dennis N. Bourdette and other members of PEHRC
Portland Environmental Hazards Research Center (PEHRC)
Deployment of military personnel is frequently associated
with significant psychosocial and physical stress. There is a paucity
of data on peripheral mediators of such stress. Alterations of the hypothalamic-pituitary-growth
hormone axis have been described in civilian patients with fibromyalgia
(FM) and may be due to chronic stress with increased CNS somatostatin
tone. Liver-derived IGF-1 is a systemic mediator of growth hormone (GH)
and is used as a screening tool for the diagnosis of GH deficiency. IGF-1
levels of 349 deployed Persian Gulf War (PGW) veterans (age=32.8+8yrs;
83%M) recruited from a population-based case-control study failed to predict
presence of unexplained musculoskeletal illnesses.
We report the results of intensive neuroendocrine axis testing
in 9 subjects with FM (39+6.3yrs) and low IGF-1 levels (131.9+29.7ng/ml)
compared to 4 controls (39+12.5yrs) with normal IGF-1 levels (236+10.9ng/ml).
Using clonidine and L-arginine, 5/9 FM and 2/4 controls failed to increase
their serum GH levels to >5ng/ml confirming the presence of adult growth
hormone deficiency. In this small sample, the mean peak GH achieved was
not different between cases and controls (4.83+4.8ng/ml vs 4.74+3.14ng/ml).
GH is normally secreted during stage-4 sleep in the mid to latter part
of sleep. Studies of 24-hour serum GH secretion have demonstrated abnormal
patterns of secretion in civilians with FM. In the current study, FM cases
have similar 24-hour GH levels but higher median levels from 8 p.m. to
2 a.m. compared to controls (0.250ng/ml vs 0.05ng/ml; p<0.001), suggesting
a phase shift in GH secretion. With larger numbers we will be able to
report more detailed results obtained by deconvolutional analysis.
The hypothalamic-pituitary-adrenal axis is another candidate
for studies of the effects of stress. We found no difference in urinary
cortisol between cases and controls (25+9.3m g/g vs 21+10.9m g/g creatinine).
The diurnal pattern of cortisol secretion also appears to be maintained
with peak levels secreted in the early morning and nadir occurring in
the early evening. Interestingly, FM cases reached a significantly lower
nadir than controls from 8 p.m. to 2 a.m. (1.5m g/dl vs 2.5m g/dl; p<0.001)
at the same time their GH levels were greater.
In conclusion, ongoing studies of neuroendocrine dysfunction
may provide important information about the influence of stress in veterans
with unexplained symptoms.
"Keywords:" Musculoskeletal Neuroendocrine
Stress Hormones
This work was supported by a grant from the Department of
Veterans Affairs to the PEHRC, a joint project of the Portland Veterans
Affairs Medical Center and the Center for Research on Occupational and
Environmental Toxicology, Oregon Health Sciences University. |
