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Review
. 2013 Sep 30:2013:784520.
doi: 10.1155/2013/784520. eCollection 2013.

A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome

Cara Tomas  1 , Julia Newton  1 , Stuart Watson  2
Affiliations
Review

A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome

Cara Tomas et al. ISRN Neurosci. .

Abstract

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been found in a high proportion of chronic fatigue syndrome (CFS) patients and includes enhanced corticosteroid-induced negative feedback, basal hypocortisolism, attenuated diurnal variation, and a reduced responsivity to challenge. A putative causal role for genetic profile, childhood trauma, and oxidative stress has been considered. In addition, the impact of gender is demonstrated by the increased frequency of HPA axis dysregulation in females. Despite the temporal relationship, it is not yet established whether the endocrine dysregulation is causal, consequent, or an epiphenomenon of the disorder. Nonetheless, given the interindividual variation in the effectiveness of existing biological and psychological treatments, the need for novel treatment strategies such as those which target the HPA axis is clear.

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Figures

Figure 1
Figure 1
The effect of stress on the hypothalamic-pituitary-adrenal axis. The hypothalamus secretes both CRH and AVP from the paraventricular nucleus which stimulate the production of ACTH in the anterior pituitary. ACTH travels via the blood until it stimulates the adrenal gland to secrete cortisol. Cortisol acts via a negative feedback mechanism mediated by MR and GR in the hypothalamus and GR in the anterior pituitary, which ultimately causes a decrease in secretion of CRH, AVP, and ACTH. CRH: corticotropin releasing hormone; AVP: arginine vasopressin; ACTH: adrenocorticotropic hormone; MR: mineralocorticoid receptor; GR: glucocorticoid receptor.
Figure 2
Figure 2
The metabolic pathway showing the steps involved in the synthesis of cortisol from cholesterol. Cholesterol is converted to pregnenolone by desmolase, which is then converted to progesterone by 3-B-hydroxysteroid. Progesterone is converted to 17-a-hydroxyprogesterone (17-OH progesterone) by 17-hydroxylase. The 17-OH progesterone is then converted to 11-deoxycortisol by the enzyme 21-hydroxylase. Finally, 11-deoxycortisol is converted into cortisol by 11-hydroxylase. DHEA: dehydroepiandrosterone.
See this image and copyright information in PMC

References

    1. Chaudhuri A, Behan PO. Neurological dysfunction in chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome. 2000;6(3-4):51–68.
    1. Atkinson HC, Leggett JD, Wood SA, Castrique ES, Kershaw YM, Lightman SL. Regulation of the hypothalamic-pituitary-adrenal axis circadian rhythm by endocannabinoids is sexually diergic. Endocrinology. 2010;151(8):3720–3727. - PMC - PubMed
    1. Ottenweller JE, Sisto SA, McCarty RC, Natelson BH. Hormonal responses to exercise in chronic fatigue syndrome. Neuropsychobiology. 2001;43(1):34–41. - PubMed
    1. Van Houdenhove B, Eede FVD, Luyten P. Does hypothalamic-pituitary-adrenal axis hypofunction in chronic fatigue syndrome reflect a ’crash’ in the stress system? Medical Hypotheses. 2009;72(6):701–705. - PubMed
    1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Annals of Internal Medicine. 1994;121(12):953–959. - PubMed