Salivary cortisol as a predictor of postoperative fatigue

 Abstract:

OBJECTIVE: Some patients with chronic fatigue syndrome (CFS) exhibit low basal cortisol levels, but it is not known whether low cortisol is a cause of CFS, predates the onset of CFS symptoms, or is an epiphenomenon caused by the behavioral changes typical of CFS. Because elective surgery is one of the few predictable risk factors for chronic fatigue, in this study, we followed a cohort of surgery patients from before to 6 months after their operation to test these theories.

METHOD: One hundred sixty-one patients completed fatigue questionnaires and provided salivary cortisol samples before undergoing an elective inpatient surgical procedure, and then 2 days, 3 weeks, and 6 months afterward.

RESULTS: Controlling for relevant demographic and surgical variables and for preoperative fatigue, low preoperative cortisol did not predict postoperative fatigue severity on any occasion (p > .05). Similarly, there was no correlation between low postoperative cortisol and postoperative fatigue severity at 3 weeks or 6 months (p > .05). Although 16 patients met our case definition for “chronic fatigue” at the 6-month follow up, low preoperative and low postoperative cortisol did not significantly predict fatigue caseness (p > .05).

CONCLUSIONS: Any association between chronic fatigue and low cortisol would seem to develop after the onset of fatigue symptoms. Low cortisol is therefore unlikely to be the primary cause of chronic fatigue states.

 

Source: Rubin GJ, Hotopf M, Papadopoulos A, Cleare A. Salivary cortisol as a predictor of postoperative fatigue. Psychosom Med. 2005 May-Jun;67(3):441-7. http://www.ncbi.nlm.nih.gov/pubmed/15911908 

 

24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome

Abstract:

OBJECTIVES: Disturbances of neuroendocrine function, particularly the hypothalamo-pituitary-adrenal (HPA) axis, have been implicated in the pathophysiology of chronic fatigue syndrome (CFS). However, few studies have attempted to measure blood levels of pituitary or adrenal hormones across a whole 24-hour period in CFS, and those that did so have used infrequent sampling periods. Our aim was to assess 24-hour pituitary and adrenal function using frequent blood sampling.

METHODS: We recruited 15 medication-free patients with CFS without comorbid psychiatric disorder and 10 healthy control subjects. Blood samples were collected over 24 hours and assayed for cortisol, corticotropin (ACTH), growth hormone (GH), and prolactin (PRL) levels on an hourly basis during daytime hours (10 am to 10 pm) and every 15 minutes thereafter (10 pm to 10 am).

RESULTS: Repeated-measures analyses of variance were undertaken using hormone levels averaged over 2-hour blocks to smooth curves by reducing the influence of sample timing relative to secretory burst. For ACTH, there was both a main effect of group, suggesting reduced mean ACTH secretion in patients with CFS over the whole monitoring period, and a group-by-time interaction, suggesting a differential pattern of ACTH release. Post hoc analysis showed reduced ACTH levels in CFS during the 8 am to 10 am period. In contrast, there were no significant abnormalities in the levels of cortisol, GH, and PRL in patients with CFS over the full cycle compared with control subjects. Cosinor analysis found no differences in the cortisol circadian rhythm parameters, but the ACTH rhythm did differ, patients with CFS showing an earlier acrophase.

CONCLUSIONS: Patients with CFS demonstrated subtle alterations in HPA axis activity characterized by reduced ACTH over a full circadian cycle and reduced levels during the usual morning physiological peak ACTH secretion. This provides further evidence of subtle dysregulation of the HPA axis in CFS. Whether this dysregulation is a primary feature of the illness or instead represents a biologic effect secondary to having the illness itself remains unclear.

 

Source: Di Giorgio A, Hudson M, Jerjes W, Cleare AJ. 24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome. Psychosom Med. 2005 May-Jun;67(3):433-40. http://www.ncbi.nlm.nih.gov/pubmed/15911907

 

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory

Abstract:

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT).

We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for.

Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99).

Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

 

Source: Lange G, Steffener J, Cook DB, Bly BM, Christodoulou C, Liu WC, Deluca J, Natelson BH. Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory. Neuroimage. 2005 Jun;26(2):513-24. Epub 2005 Apr 7. http://www.ncbi.nlm.nih.gov/pubmed/15907308

 

Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution

Abstract:

BACKGROUND: A recent article by Reeves et al. on the identification and resolution of ambiguities in the 1994 chronic fatigue syndrome (CFS) research case definition recommended the Checklist Individual Strength, the Chalder Fatigue Scale, and the Krupp Fatigue Severity Scale for evaluating fatigue in CFS studies. To be able to discriminate between various levels of severe fatigue, extreme scoring on the individual items of these questionnaires must not occur too often.

METHODS: We derived an expression that allows us to compute a lower bound for the number of items with the maximum item score for a given study from the reported mean scale score, the number of reported subjects, and the properties of the fatigue rating scale. Several CFS studies that used the recommended fatigue rating scales were selected from literature and analyzed to verify whether abundant extreme scoring had occurred.

RESULTS: Extreme scoring occurred on a large number of the items for all three recommended fatigue rating scales across several studies. The percentage of items with the maximum score exceeded 40% in several cases. The amount of extreme scoring for a certain scale varied from one study to another, which suggests heterogeneity in the selected subjects across studies.

CONCLUSION: Because all three instruments easily reach the extreme ends of their scales on a large number of the individual items, they do not accurately represent the severe fatigue that is characteristic for CFS. This should lead to serious questions about the validity and suitability of the Checklist Individual Strength, the Chalder Fatigue Scale, and the Krupp Fatigue Severity Scale for evaluating fatigue in CFS research.

Comment on: Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. [BMC Health Serv Res. 2003]

 

Source: Stouten B. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2005 May 13;5:37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175848/ (Full article)

 

Prospective observational study of treatments for unexplained chronic fatigue

Abstract:

BACKGROUND: Unexplained chronic fatigue is a frequent complaint in primary care. A prospective observational study design was used to evaluate whether certain commonly used therapies for unexplained chronic fatigue may be effective.

METHOD: Subjects with unexplained chronic fatigue of unknown etiology for at least 6 months were recruited from the Wisconsin Chronic Fatigue Syndrome Association, primary care clinics, and community chronic fatigue syndrome presentations. The primary outcome measure was change in a 5-question fatigue score from 6 months to 2 years. Self-reported interventions tested included prescribed medications, non-prescribed supplements and herbs, lifestyle changes, alternative therapies, and psychological support. Linear regression analysis was used to test the association of each therapy with the outcome measure after adjusting for statistically significant prognostic factors.

RESULTS: 155 subjects provided information on fatigue and treatments at baseline and follow-up. Of these subjects, 87% were female and 79% were middle-aged. The median duration of fatigue was 6.7 years. The percentage of users who found a treatment helpful was greatest for coenzyme Q10 (69% of 13 subjects), dehydroepiandrosterone (DHEA) (65% of 17 subjects), and ginseng (56% of 18 subjects). Treatments at 6 months that predicted subsequent fatigue improvement were vitamins (p = .08), vigorous exercise (p = .09), and yoga (p = .002). Magnesium (p = .002) and support groups (p = .06) were strongly associated with fatigue worsening from 6 months to 2 years. Yoga appeared to be most effective for subjects who did not have unclear thinking associated with the fatigue.

CONCLUSION: Certain alternative therapies for unexplained chronic fatigue, especially yoga, deserve testing in randomized controlled trials.

 

Source: Bentler SE, Hartz AJ, Kuhn EM. Prospective observational study of treatments for unexplained chronic fatigue. J Clin Psychiatry. 2005 May;66(5):625-32. http://www.ncbi.nlm.nih.gov/pubmed/15889950

 

Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression

Abstract:

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a commonly recognized feature of many pathological conditions. Abnormal adrenal responses to experimental manipulation have been well documented in patients suffering from chronic fatigue syndrome, anorexia nervosa and major depression. Yet no defect of any single organ, gland or brain region has been identified as a cause of these abnormalities. The disruption of the HPA axis that occurs in these conditions can be understood if an interfering factor is present in these patients.

Evidence indicates that this interfering factor is adrenocorticotropin hormone (ACTH) autoantibodies. Chronic high levels of ACTH autoantibodies will significantly disrupt the HPA axis and force the body to compensate for an impaired cortisol response. The resulting effect of chronic ACTH autoantibody interference is the manifestation of adrenocortical insufficient symptoms and psychological disturbances. Some symptoms ofchronic fatigue syndrome, anorexia nervosa and major depression, such as anxiety, are the adverse effects of mechanisms compensating for less effective ACTH due to autoantibodies. Furthermore, these patients engage in extraordinary behaviors, such as self-injury, to increase their cortisol levels. When this compensation is inadequate, symptoms of adrenocortical insufficiency appear.

Corticosteroid supplements have been demonstrated to be an effective treatment for chronic fatigue syndrome, anorexia nervosa and major depression. It allows the patients to have the corticosteroids they require for daily functioning and daily stressors. This therapy will relieve the patients of their symptoms of adrenocortical insufficiency and permit their cortisol-stimulating mechanisms to operate at levels that will not cause pathological problems.

 

Source: Wheatland R. Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression. Med Hypotheses. 2005;65(2):287-95. http://www.ncbi.nlm.nih.gov/pubmed/15885924

 

Green tea extract and catechin ameliorate chronic fatigue-induced oxidative stress in mice

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear, but a number of studies have shown that oxidative stress may be involved in its pathogenesis. The present study was designed to investigate the protective effect of green tea extract (GTE) and catechin in the mouse model of CFS.

Animals were subjected to a forced swimming test session of 6 minutes every day for 7 days; a significant increase in immobility time on successive days represented the CFS in mice. Biochemical analysis revealed that the chronic swim test significantly increased lipid peroxidation levels and decreased glutathione levels in mouse whole-brain homogenate.

Treatment with GTE (25 or 50 mg/kg, i.p.) and catechin (50 or 100 mg/kg, i.p.) for 7 days reversed the increase in immobility time. Protection was correlated with the lowered levels of lipid peroxidation and restoration of reduced glutathione levels in the brains of fatigued mice. These findings strongly suggest the pivotal role of oxidative stress in the pathophysiology of CFS and that GTE and catechin could be used as potential agents in the management of CFS and warrant the inclusion of GTE and catechin in the treatment regimen of CFS patients.

 

Source: Singal A, Kaur S, Tirkey N, Chopra K. Green tea extract and catechin ameliorate chronic fatigue-induced oxidative stress in mice. J Med Food. 2005 Spring;8(1):47-52. http://www.ncbi.nlm.nih.gov/pubmed/15857209

 

Qi therapy (external qigong) for chronic fatigue syndrome: case studies

Abstract:

The aim of this study was to examine the effects of Qi therapy (QT) on the symptoms of chronic fatigue syndrome (CFS), including fatigue and complications. QT affected the experience of mental and emotional relaxation in the subjects of these case studies, who also gained strength to overcome their pain and fatigue. Although the results of these two case studies may not constitute conclusive evidence, they provide a foundation for the exploration of QT as a complementary therapy in the reduction of negative symptoms of chronic fatigue syndrome.

 

Source: Shin YI, Lee MS. Qi therapy (external qigong) for chronic fatigue syndrome: case studies. Am J Chin Med. 2005;33(1):139-41. http://www.ncbi.nlm.nih.gov/pubmed/15844841

 

Report from the Health Council of the Netherlands on the chronic fatigue syndrome: moving away from the body-mind dichotomy with a view to effective prevention and treatment

Abstract:

The Health Council of the Netherlands has issued a report on the chronic fatigue syndrome (CFS). CFS is a real and seriously debilitating condition which imposes limitations on an individual’s personal, occupational and social functioning. It is a syndrome of unknown aetiology without physical signs or biological markers. Although there is no disease, patients both feel ill and give the appearance of being ill. There is no consensus on whether CSF patients are able to work or whether they should be entitled to social security benefits. An imbalance between demand and coping is central in CFS, with stress as an important intermediary factor. It is little use concluding that unexplained signs are ‘psychological’ or that ‘I cannot find anything wrong with you so you must be healthy’. The classical view that mind and body are separate systems is outmoded. The bio-psycho-social model of disease may be helpful in describing the interaction between body, mind and circumstance. Putting the CFS patient at ease and explaining the pathophysiology of the symptoms is a useful approach but many patients and patient associations are still very somatically orientated, thereby sustaining the condition. However, in patients who accept that their problems may be stress-induced and are prepared to participate in therapy, some therapies have been proven to be effective, notably cognitive behavioural therapy.

 

Source: Bolk JH. Report from the Health Council of the Netherlands on the chronic fatigue syndrome: moving away from the body-mind dichotomy with a view to effective prevention and treatment. Ned Tijdschr Geneeskd. 2005 Apr 2;149(14):739-41. [Article in Dutch] http://www.ncbi.nlm.nih.gov/pubmed/15835623

 

Disturbed adrenal function in adolescents with chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate adrenal function in children and adolescents with chronic fatigue syndrome (CFS) compared with age-matched controls.

METHODS: Case-control study of low dose (500 ng/m2) synacthen tests (LDST) in 23 adolescents with CFS and 17 age-matched controls. Serum cortisol concentrations were measured at 5-min intervals from 10 to 45 minutes. Peak serum cortisol concentration, time to peak, rise in cortisol and area under the curve (AUC) were derived.

RESULTS: Patients with CFS had significantly lower mean cortisol levels during the LDST (p <0.001), lower peak cortisol (p <0.025), reduced cortisol AUC (p <0.005) and longer time to peak cortisol (p <0.05). Abnormalities were seen in both sexes but were more pronounced in females. Unstimulated adrenal androgen and 17-hydroxyprogesterone concentrations were normal.

CONCLUSIONS: Adolescents with CFS have subtle alterations in adrenal function suggesting a reduction in central stimulation of the adrenal glands. The more pronounced effects in females may reflect differential central effects of stress on hypothalamic-pituitary-adrenal axis regulation between the sexes.

 

Source: Segal TY, Hindmarsh PC, Viner RM. Disturbed adrenal function in adolescents with chronic fatigue syndrome. J Pediatr Endocrinol Metab. 2005 Mar;18(3):295-301. http://www.ncbi.nlm.nih.gov/pubmed/15813608