Pituitary-Adrenal Function in Gulf War Veterans with Medically Unexplained Symptoms
Principal Investigator: Shelley A. Weaver, PhD & Benjamin H. Natelson, MD
Objective: Following the Gulf War, many soldiers returned home with a number of different medically unexplained complaints. As part of the mission of the New Jersey Environmental Hazards Research Center, we investigated and confirmed our hypothesis that some of the Gulf veterans (GVs) would fulfill the case definition for chronic fatigue syndrome or idiopathic chronic fatigue (CFS/ICF). Much is known about CFS/ICF in civilians, and some of that information might be relevant to GVs with CFS/ICF. One set of studies, although not definitive, suggests a role for cortisol, the major adrenocortical hormone, in the genesis of CFS/ICF. Because CFS/ICF in GVs has differences from that seen in civilians (e.g., quasi-epidemic onset in GVs, more men, more minorities), it is possible that data collected in civilians cannot be directly applied to GVs. Thus the purpose of this proposal is to evaluate the hypothalamo-pituitary-adrenal (HPA) axis in GVs with CFS/ICF.
Research Plan: We will be comparing data collected from GVs to data collected from non-veterans with CFS/ICF. To do this requires our dealing with gender difference between GVs and civilians with CFS/ICF. We have not identified enough female GVs with CFS/ICF to allow a complete design. Instead, we plan to collect data from non-veteran men and women with CFS/ICF and to compare those results with data collected from healthy male and female controls.
Method: In all our studies, we will compare patients with CFS/ICF with appropriately matched controls. We will use a standard endocrinological approach to evaluate the HPA axis in GVs. We will do our evaluation on two visits to the center - the order of which will be decided by a coin flip. The first study done on one of the visits, uses frequent blood sampling (i.e., every 10 min for 24 hr) to deal with the variability in results from previous studies. Those studies usually sampled only several times, and it is well known that spot sampling does not accurately represent ACTH or cortisol levels as these hormones are secreted episodically in an ultradian rhythm. Immediately after the end of this baseline data collection period, we will continue blood sampling after an ovine CRH challenge. On another visit to the Center, we will ask the subject to take 1 mg of dexamethason to suppress endogenous ACTH and allow us to follow the adrenal cortical response to low dose ACTH change the next morning.
Impact: At the end of this merit review, we should have clear-cut data on the HPA function in patients with CFS/ICF. First, we will know if males with CFS/ICF have the same endocrine dysfunction as had been reported in females with CFS/ICF. Next, we will know if GVs with this illness have the same pituitary-adrenal profile as age and sex matched non-veterans with this illness. If we find quantitatively similar results, this will suggest that the pathogenesis of the illness is similar in the two illness groups. If, in contrast, we find differences from controls in non-veterans but not in GVs, this outcome would suggest that GVs have their problems due to something other than neuroendrocrine abnormalities. Having empirical data about the pathophysiology of CFS/ICF - especially as it pertains to GVs - would be helpful to VA planners anxious to respond to the veterans' calls of action concerning their unexplained illness.
Status: Project is ongoing.