Tag: HPA axis

Pathogenic tracks in fatigue syndromes

Abstract:

This review analyses the recent literature devoted to two related fatigue syndromes: chronic fatigue syndrome (CFS) and acute onset postviral fatigue syndrome (PVFS). The articles are grouped into five pathogenic tracks: infectious agents, immune system, skeletic muscle, hypothalamo-pituitary-adrenal (HPA) axis and psychiatric factors.

Although a particular infectious agent is unlikely to be responsible for all CFS cases, evidence is shown that host-parasite relationships are modified in a large proportion of patients with chronic fatigue. Antibody titres against infectious agents are often elevated and replication of several viruses could be increased.

Chronic activation of the immune system is also observed and could be due to the reactivation of persistent or latent infectious agents such as herpes viruses (i.e. HHV-6) or enteroviruses. It could also be favorised by an impaired negative feedback of the HPA axis on the immune system.

A model is proposed where the abnormalities of the HPA axis are primary events and are mainly responsible for a chronic activation of the immune system which in turn induces an increased replication of several viruses under the control of cellular transcription factors. These replicating viruses together with cytokines such as TNF-alpha would secondarily induce functional disorders of muscle and several aspects of asthenia itself.

 

Source: Moutschen M, Triffaux JM, Demonty J, Legros JJ, Lefèbvre PJ. Pathogenic tracks in fatigue syndromes. Acta Clin Belg. 1994;49(6):274-89. http://www.ncbi.nlm.nih.gov/pubmed/7871934

 

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome

Abstract:

Operational diagnostic criteria for fibromyalgia were applied to most clinical studies during the past year. Similar diagnostic criteria for chronic fatigue syndrome are being revised, but criteria for myofascial pain have not been agreed on or tested. Intense research efforts focused on the role of neurohormones and the hypothalamic-pituitary-adrenal axis in fibromyalgia and chronic fatigue syndrome over the past year.

 

Source: Goldenberg DL. Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Curr Opin Rheumatol. 1993 Mar;5(2):199-208. http://www.ncbi.nlm.nih.gov/pubmed/8452771

 

Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome

Abstract:

Abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis are a well recognised feature of endogenous depression. The mechanism underlying this phenomenon remains obscure although there is strong evidence suggesting excessive CRH activity at the level of the hypothalamus.

We propose a novel hypothesis in which we suggest that the aetiological antecent to CRH hyperactivity is cytokine activation in the brain. It is now well established both that interleukins -1 and -6 are produced in a number of central loci and that cytokines are potent stimulators of the HPA axis.

Hence, we suggest that activation of IL-1 and IL-6 by specific mechanisms (such as neurotropic viral infection) in combination with the consequent CRH-41 stimulation, may (via their known biological effects) underly many of the features found in major depression and other related disorders, particularly where chronic fatigue is a prominent part of the symptom complex.

This theory has considerable heuristic value and suggests a number of experimental stratagems which may employed in order to confirm or reject it.

 

Source: Ur E, White PD, Grossman A. Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. Eur Arch Psychiatry Clin Neurosci. 1992;241(5):317-22. http://www.ncbi.nlm.nih.gov/pubmed/1606197

 

Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is characterized by persistent or relapsing debilitating fatigue for at least 6 months in the absence of a medical diagnosis that would explain the clinical presentation. Because primary glucocorticoid deficiency states and affective disorders putatively associated with a deficiency of the arousal-producing neuropeptide CRH can be associated with similar symptoms, we report here a study of the functional integrity of the various components of the hypothalamic-pituitary-adrenal axis in patients meeting research case criteria for chronic fatigue syndrome.

Thirty patients and 72 normal volunteers were studied. Basal activity of the hypothalamic-pituitary-adrenal axis was estimated by determinations of 24-h urinary free cortisol-excretion, evening basal plasma total and free cortisol concentrations, and the cortisol binding globulin-binding capacity. The adrenal cortex was evaluated indirectly by cortisol responses during ovine CRH (oCRH) stimulation testing and directly by cortisol responses to graded submaximal doses of ACTH. Plasma ACTH and cortisol responses to oCRH were employed as a direct measure of the functional integrity of the pituitary corticotroph cell. Central CRH secretion was assessed by measuring its level in cerebrospinal fluid.

Compared to normal subjects, patients demonstrated significantly reduced basal evening glucocorticoid levels (89.0 +/- 8.7 vs. 148.4 +/- 20.3 nmol/L; P less than 0.01) and low 24-h urinary free cortisol excretion (122.7 +/- 8.9 vs. 203.1 +/- 10.7 nmol/24 h; P less than 0.0002), but elevated basal evening ACTH concentrations.

There was increased adrenocortical sensitivity to ACTH, but a reduced maximal response [F(3.26, 65.16) = 5.50; P = 0.0015). Patients showed attenuated net integrated ACTH responses to oCRH (128.0 +/- 26.4 vs. 225.4 +/- 34.5 pmol/L.min, P less than 0.04). Cerebrospinal fluid CRH levels in patients were no different from control values (8.4 +/- 0.6 vs. 7.7 +/- 0.5 pmol/L; P = NS).

Although we cannot definitively account for the etiology of the mild glucocorticoid deficiency seen in chronic fatigue syndrome patients, the enhanced adrenocortical sensitivity to exogenous ACTH and blunted ACTH responses to oCRH are incompatible with a primary adrenal insufficiency. A pituitary source is also unlikely, since basal evening plasma ACTH concentrations were elevated.

Hence, the data are most compatible with a mild central adrenal insufficiency secondary to either a deficiency of CRH or some other central stimulus to the pituitary-adrenal axis. Whether a mild glucocorticoid deficiency or a putative deficiency of an arousal-producing neuropeptide such as CRH is related to the clinical symptomatology of the chronic fatigue syndrome remains to be determined.

 

Source: Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi MJ, Chrousos GP, Gold PW. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab. 1991 Dec;73(6):1224-34. http://www.ncbi.nlm.nih.gov/pubmed/1659582