The model presented by Ben-Zvi et al. provides an interesting look at how HPA axis dysfunction could occur and be corrected. The question is, do real CFS cases fit this model? While cortisol levels have been relatively well studied in the CFS population, few studies have explicitly measured glucocorticoid receptor levels or associated gene expression.

Jason et al. found in a study of adolescents with CFS (mean age = 17.8), that despite low mean cortisol levels, the gene expression of NR3C1 as well as NFKB1,NFKB2 was down regulated [2].

Kavelaars et al. found decreased sensitivity to GC and a ß2-adrenergic receptor agonist in paediatric patients with CFS (mean age = 15.8), compared to matched controls [3]. Kavelaars et al. suggested this is either due to a reduced number of receptors, or that the transduction from the receptor to the effector system was diminished [3].

Visser et al. found that there was increased susceptibility to dexamethasone suppression of PBMC proliferation in CFS patients compared to controls. However no statistically significant difference in the density or affinity of glucocorticoid receptors was found [4].

In addition, Rajeevan et al. found multiple SNPs associated with CFS, compared to healthy controls [5]. However the significance of these SNPs is unknown.

According to the model presented by Ben-Zvi et al., the explanation for the combined low cortisol and GR expression is if CFS patients had simply been exposed to less environmental stressors. This is a reasonable explanation, since many CFS patients are unemployed and many of them leave the house infrequently. In healthy subjects, differences in salivary cortisol have been noted depending on whether the samples were taken on a weekday or weekend. Unfortunately, many of the studies reporting cortisol abnormalities tested on weekdays and did not control for employment status.

It is possible that the HPA abnormalities are simply an artefact of low activity levels, or SNPs in some patients, or even due to other underlying aspects of the disorder.
Only more comprehensive studies investigating HPA dysfunction in CFS patients will answer this question.

References

[1] A Ben-Zvi , SD Vernon, G Broderick. Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction. PLoS Computational Biology. 2009, 5(1): e1000273. doi:10.1371/journal.pcbi.1000273
[2] L Jason, M Sorenson, N Porter, M Brown, A Lerch, C Van der Eb, J Mikovits. Possible Genetic Dysregulation in Pediatric CFS. Psychology, 2010, 1, 247-251
[3] A Kavelaars, W Kuis, L Knook, G Sinnema and C Heijnen. Disturbed Neuroendocrine-Immune Interactions in Chronic Fatigue Syndrome. Journal of Clinical Endocrinology & Metabolism, 2000, 85, 692-696
[4] J Visser, E Lentjes, I Haspels, W Graffelman, B Blauw, R de Kloet, L Nagelkerken. Increased Sensitivity to Glucocorticoids in Peripheral Blood Mononuclear Cells of Chronic Fatigue Syndrome Patients, Without Evidence for Altered Density or Affinity of Glucocorticoid Receptors, Journal of Investigative Medicine, 2001, 49, 195-204
[5] MS Rajeevan, AK Smith, I Dimulescu, ER Unger, SD Vernon, C Heim, WC Reeves. Glucocorticoid receptor polymorphisms and haplotypes associated with chronic fatigue syndrome, 2007, Genes, Brain and Behavior 6(2), 167–176