Levels of DHEA and DHEAS and responses to CRH stimulation and hydrocortisone treatment in chronic fatigue syndrome

Abstract:

BACKGROUND: An association between chronic fatigue syndrome (CFS) and abnormalities of the hypothalamo-pituitary-adrenal axis has been described, and other adrenal steroid abnormalities have been suggested. Dehydroepiandrostenedione (DHEA) and its sulphate (DHEA-S), apart from being a precursor of sex steroids, have other functions associated with memory, depression and sleep. It has been suggested that CFS may be associated with a state of relative DHEA(-S) deficiency. Therefore we investigated basal levels of DHEA(-S), the cortisol/DHEA molar ratio and the responsiveness of DHEA to stimulation by corticotrophin-releasing hormone (CRH). Recent studies have also suggested that low dose hydrocortisone may be effective at reducing fatigue in CFS. We therefore also assessed these parameters prior to and following treatment with low dose oral hydrocortisone.

METHODS: Basal levels of serum DHEA, DHEAS and cortisol were measured in 16 patients with CFS without depression and in 16 controls matched for age, gender, weight, body mass index and menstrual history. CRH tests (1 g/kg i.v.) were carried out on all subjects and DHEA measured at 0, +30 and +90 min. In the patient group, CRH tests were repeated on two further occasions following treatment with hydrocortisone (5 or 10 mg, p.o.) or placebo for 1 month each in a double-blind cross over study protocol.

RESULTS: Basal levels of DHEA were higher in the patient, compared to the control, group (14.1+/-2.2 vs. 9.0+/-0.90 ng/ml, P=0.04), while levels of DHEAS in patients (288.7+/-35.4 microg/dl) were not different from controls (293.7+/-53.8, P=NS). Higher DHEA levels were correlated with higher disability scores. Basal cortisol levels were higher in patients, and consequently the cortisol/DHEA molar ratio did not differ between patients and controls. Levels of DHEA (8.9+/-0.97 ng/ml, P=0.015) and DHEAS (233.4+/-41.6 microg/dl, P=0.03) were lower in patients following treatment with hydrocortisone. There was a rise in DHEA responsiveness to CRH in the patients after treatment but this did not attain significance (AUCc: 2.5+/-1.7 ng/ml h pre-treatment vs. 6.4+/-1.2 ng/ml h post-hydrocortisone, P=0.053). However, those patients who responded fully to hydrocortisone in terms of reduced fatigue scores did show a significantly increased DHEA responsiveness to CRH (AUCc: -1.4+/-2.5 ng/ml h at baseline, 5.0+/-1.2 ng/ml h after active treatment, P=0.029).

CONCLUSIONS: DHEA levels are raised in CFS and correlate with the degree of self-reported disability. Hydrocortisone therapy leads to a reduction in these levels towards normal, and an increased DHEA response to CRH, most marked in those who show a clinical response to this therapy.

 

Source: Cleare AJ, O’Keane V, Miell JP. Levels of DHEA and DHEAS and responses to CRH stimulation and hydrocortisone treatment in chronic fatigue syndrome. Psychoneuroendocrinology. 2004 Jul;29(6):724-32. http://www.ncbi.nlm.nih.gov/pubmed/15110921

 

Impairment and coping in children and adolescents with chronic fatigue syndrome: a comparative study with other paediatric disorders

Abstract:

BACKGROUND: Functional impairment is a key feature of chronic fatigue syndrome (CFS) of childhood.

AIM: To compare impairment, illness attitudes and coping mechanisms in childhood CFS and in other paediatric disorders.

METHOD: Participants were 28 children and adolescents with CFS, 30 with juvenile idiopathic arthritis (JIA) and 27 with emotional disorders (ED). The measures used were interviews with children and parents, with detailed enquiry on impairment, including the Functional Disability Inventory (FDI), Illness Attitudes Scales (IAS), and Kidcope to measure coping styles in relation to common problems, illness and disability.

RESULTS: Children with CFS reported significantly more illness impairment, especially in school attendance, than those with JIA and ED. They had higher ‘worry about illness’ scores on the IAS. On the Kidcope they named school issues (work, expectations, attendance) as illness- or disability-related problems more than the other two groups. Fewer CFS participants reported using problem solving as a strategy to cope with illness and disability than with other problems in their lives. More in the CFS than in the JIA group used emotional regulation to cope with illness and disability. Fewer in the CFS than in the ED groups used social withdrawal to cope with illness and self-criticism for disability, but more used resignation to cope with disability.

CONCLUSION: Severe illness-related impairment, particularly through school non-attendance, and high levels of illness-related school concerns appear specific to CFS. CFS may also have characteristically high levels of generalised illness worry and particular styles of coping with illness and disability.

 

Source: Garralda ME, Rangel L. Impairment and coping in children and adolescents with chronic fatigue syndrome: a comparative study with other paediatric disorders. J Child Psychol Psychiatry. 2004 Mar;45(3):543-52. http://www.ncbi.nlm.nih.gov/pubmed/15055373

 

Disability evaluation in chronic fatigue syndrome: associations between exercise capacity and activity limitations/participation restrictions

Abstract:

OBJECTIVE: In an attempt to examine whether impairments in cardiorespiratory fitness are associated with daily functioning in patients with chronic fatigue syndrome (CFS), this study addresses the correlations between exercise capacity and activity limitations/participation restrictions.

DESIGN: Prospective observational study.

SETTING: An outpatient tertiary care, chronic fatigue clinic at the Vrije Universiteit Brussel (VUB), Belgium.

SUBJECTS: Seventy-seven patients fulfilling the 1994 Centers for Disease Control and Prevention (CDC) case definition for CFS.

INTERVENTIONS: All patients filled in the Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ) and performed a maximal exercise stress test on a bicycle ergometer. Heart rate was monitored continuously by use of an electrocardiograph. Metabolic and ventilatory parameters were measured through spirometry.

RESULTS: A statistically significant correlation between the score obtained with the CFS-APQ and the body weight-adjusted peak oxygen uptake (Spearman rho = -0.32; p = 0.005), functional aerobic impairment (rho = 0.33; p = 0.004), workload/body weight (rho = -0.30; p = 0.009), exercise duration (rho = -0.30; p = 0.008), and the percentage of target heart rate achieved (rho = -0.33; p = 0.004) was observed. The correlations between the remaining exercise capacity parameters and the scores obtained with the CFS-APQ all indicated a trend towards association (0.01 <p<0.05).

CONCLUSIONS: These results suggest a moderate association between exercise capacity and activity limitations/participation restrictions in patients with CFS. The observed correlations lack strength to predict activity limitations/ participation restriction based on exercise capacity parameters. Disability evaluation in CFS should therefore encompass both exercise capacity testing and measurements at the activity/participation dimension.

 

Source: Nijs J, De Meirleir K, Wolfs S, Duquet W. Disability evaluation in chronic fatigue syndrome: associations between exercise capacity and activity limitations/participation restrictions. Clin Rehabil. 2004 Mar;18(2):139-48. http://www.ncbi.nlm.nih.gov/pubmed/15053122

 

Illness perceptions and levels of disability in patients with chronic fatigue syndrome and rheumatoid arthritis

Abstract:

OBJECTIVE: To investigate the strength of chronic fatigue syndrome (CFS) patients’ negative illness perceptions by comparing illness perceptions and self-reported disability in patients with CFS and rheumatoid arthritis (RA).

METHODS: Seventy-four RA patients and 49 CFS patients completed the Illness Perception Questionnaire-Revised and the 36-item Short-Form Health Survey.

RESULTS: When compared to the RA group, the CFS group attributed a wider range of everyday somatic symptoms to their illness, perceived the consequences of their illness to be more profound and were more likely to attribute their illness to a virus or immune system dysfunction. Both groups reported equivalent levels of physical disability but the CFS group reported significantly higher levels of role and social disability.

CONCLUSION: Although the symptoms of CFS are largely medically unexplained, CFS patients have more negative views about their symptoms and the impact that these have had on their lives than do patients with a clearly defined and potentially disabling medical condition. The data support the cognitive behavioural models of CFS that emphasise the importance of patients’ illness perceptions in perpetuating this disorder.

 

Source: Moss-Morris R, Chalder T. Illness perceptions and levels of disability in patients with chronic fatigue syndrome and rheumatoid arthritis. J Psychosom Res. 2003 Oct;55(4):305-8. http://www.ncbi.nlm.nih.gov/pubmed/14507540

 

Functional status, neuropsychological functioning, and mood in chronic fatigue syndrome (CFS): relationship to psychiatric disorder

Abstract:

Individuals with chronic fatigue syndrome (CFS) face chronic physical debilitation, reduced neuropsychological functioning, and changes in emotional well-being that significantly detract from quality of life. The role of psychiatric disturbance in reducing quality of life in CFS remains unclear. In the current investigation, the role of psychiatric status in reducing health-related quality of life in CFS was examined.

Four subject groups were compared on measures of functional well-being, mood, and neuropsychological status: individuals with CFS and no history of psychiatric illness, individuals who had current symptoms of psychiatric illness that began after their CFS diagnosis, individuals who had current symptoms of psychiatric illness that began before their CFS diagnosis, and a healthy sedentary control group.

Overall, it was found that individuals with CFS suffer from profound physical impairment. Concurrent psychiatric illness, however, did not adversely affect physical functional capacity. Physical functional capacity was not worse in individuals with a concurrent psychiatric illness. As expected, concurrent psychiatric illness was found to reduce emotional well-being. Moreover, individuals with a psychiatric illness that predated the onset of CFS suffered the greatest emotional distress. Thus, an individual’s psychiatric history should be considered when attempting to understand the factors maintaining disability in CFS.

 

Source: Tiersky LA, Matheis RJ, Deluca J, Lange G, Natelson BH. Functional status, neuropsychological functioning, and mood in chronic fatigue syndrome (CFS): relationship to psychiatric disorder. J Nerv Ment Dis. 2003 May;191(5):324-31. http://www.ncbi.nlm.nih.gov/pubmed/12819552

 

Financial, occupational, and personal consequences of disability in patients with chronic fatigue syndrome and fibromyalgia compared to other fatiguing conditions

Abstract:

OBJECTIVE: To examine the nature and degree of self-reported disability in patients with chronic fatigue syndrome (CFS) and its associated conditions, fibromyalgia (FM) and subsyndromal fatigue (CF), compared with a chronically fatiguing but unrelated medical condition (MED).

METHODS: Six hundred and thirty patients evaluated at the University of Washington Chronic Fatigue Clinic were sent questionnaires asking them to identify the financial, occupational, and personal consequences of their fatiguing illness. Thorough medical evaluations had previously applied accepted criteria for defining CFS, FM, and CF.

RESULTS: The FM groups (those with and without CFS) were among the least employed. Likewise, the FM and CFS groups, more frequently than the other groups, endorsed loss of material possessions (such as car), loss of job, and loss of support by friends and family, as well as recreational activities as a result of their fatiguing illness. There were no reliable differences between groups in use of disability benefits.

CONCLUSION: There is substantial illness-related disability among those evaluated at a specialized chronic fatigue clinic. Those reporting the most pervasive disability met criteria for FM either alone or in conjunction with CFS. Employers and personal relations of patients with chronic fatigue should make a greater effort to accommodate the illness-related limitations of these conditions, especially for those with FM and CFS.

 

Source: Assefi NP, Coy TV, Uslan D, Smith WR, Buchwald D. Financial, occupational, and personal consequences of disability in patients with chronic fatigue syndrome and fibromyalgia compared to other fatiguing conditions. J Rheumatol. 2003 Apr;30(4):804-8. http://www.ncbi.nlm.nih.gov/pubmed/12672203

 

Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine

Abstract:

OBJECTIVE: To compare adolescents with migraine, unexplained profound chronic fatigue of >6 months duration, and normal school controls on measures of anxiety, depression, somatization, functional disability, and illness attribution.

METHODS: Adolescents referred to Children’s Hospital and Regional Medical Center for behavioral treatment of migraine (n = 179) or evaluation of chronic fatigue (n = 97) were compared with a group of healthy controls of similar age and sex from a middle school (n = 32). Subjects completed the Spielberger State-Trait Anxiety Inventory-Trait Form, the Children’s Depression Inventory, the Childhood Somatization Inventory, and estimated the number of school days missed in the past 6 months because of illness. Migraine and fatigued subjects completed an illness attribution questionnaire.

RESULTS: Subjects in the 3 groups were 56% to 70% female and ranged from 11 years old to 18 years old with a mean age of 14.0 +/- 2.0. Forty-six of the 97 chronically fatigued adolescents met 1994 Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome (CDC-CFS), while 51 had idiopathic chronic fatigue syndrome (I-CFS) that did not meet full CDC criteria. Adolescents with migraine had significantly higher anxiety scores than those with I-CFS or controls and higher somatization scores than controls. Adolescents with CDC-CFS had significantly higher anxiety scores than those with I-CFS or controls, and higher depression and somatization scores than all other groups. There were significant differences between all groups for school days missed with CDC-CFS more than I-CFS more than migraine more than controls. Parents of adolescents with unexplained I-CFS had significantly lower attribution scores relating illness to possible psychological or stress factors than parents of adolescents with CDC-CFS or migraine.

CONCLUSIONS: Adolescents referred to an academic center for evaluation of unexplained chronic fatigue had greater rates of school absenteeism than adolescents with migraine or healthy controls. Those meeting CDC-CFS criteria had higher anxiety scores than controls and higher depression and somatization scores than migraineurs or controls. Parents of adolescents with I-CFS were less likely to endorse psychological factors as possibly contributing to their symptoms than parents of adolescents with CDC-CFS or migraine.

 

Source: Smith MS, Martin-Herz SP, Womack WM, Marsigan JL. Comparative study of anxiety, depression, somatization, functional disability, and illness attribution in adolescents with chronic fatigue or migraine. Pediatrics. 2003 Apr;111(4 Pt 1):e376-81. http://www.ncbi.nlm.nih.gov/pubmed/12671155

 

Systematic review of the current literature related to disability and chronic fatigue syndrome

Abstract:

Objective: The objective of this evidence report was to perform a systematic review of the published literature to provide the Social Security Administration (SSA) with the best available evidence and most current medical knowledge regarding disability in persons with Chronic Fatigue Syndrome (CFS).

Search Strategy: English language and adult population published literature from 1988 to November 2001 was searched using MEDLINE, Current Contents, Cochrane Library, and PsychINFO databases and supplemented by a manual review of bibliographies of all accepted papers.

Selection Criteria: Interventional or observational studies of at least two adult patients reporting CFS according to either the CDC 1988, CDC 1994, Oxford 1991, or Australia 1990 criteria were accepted. Studies were required to report disability (evidence of a medically determinable physical or mental impairment) and data regarding employment or work.

Data Collection and Analysis: Data on patients, interventions, and outcomes were extracted from accepted studies. Studies were scored for quality and level of evidence. Data were summarized for study, patient, and treatment level characteristics as well as outcomes of interest. A panel of diverse technical experts and peer reviewers provided review and commentary on the draft report.

Main Results: Of 3,840 citations identified, 53 studies describing 4,558 patients with CFS met all eligibility criteria. Twenty-two of these studies described comparator groups of healthy controls totaling 775 patients. The majority of CFS patients represented in the 37 studies reporting employment status were unemployed. The evidence suggests that some individuals with CFS have cognitive or affective impairments on neuropsychological tests, but results are not consistent. Depression of greater severity is associated with unemployment, but no other impairment appeared to be consistently associated with disability or work outcomes. No specific interventions have been proven to be effective in restoring the ability to work. No specific patient characteristics have been identified as best predictors of positive employment outcomes in CFS patients. The patient’s level of functioning at the time of diagnosis should be compared to functioning prior to the onset of illness especially as it relates to work, school, social and home activities.

The major limitations of this review are related to the weaknesses inherent in the current medical and scientific published literature regarding CFS. Study designs were not sufficiently homogeneous to allow quantitative synthesis of individual study results, and external validity was low. While some studies reported test and scale results, this was highly variable with relatively sparse and inconsistent reporting of both baseline and outcome data. No studies specifically measured the impact of baseline impairment data or treatment interventions on work function or employment outcomes.

Conclusions: While relationships between various impairment measures and work/disability status might be explored in some cases, the best available evidence from the literature did not allow for determination of causality. The limitations inherent in the current literature review are noted and the research community is urged to conduct methodologically rigorous, longitudinal, interventional studies to determine what baseline characteristics are associated with inability to work, and what interventions are effective in restoring the ability to work in the CFS population.

 

Source: Ross SD, Levine C, Ganz N, Frame D, Estok R, Stone L, Ludensky V. Systematic review of the current literature related to disability and chronic fatigue syndrome. Evid Rep Technol Assess (Summ). 2002 Dec;(66):1-3. http://www.ncbi.nlm.nih.gov/books/NBK36735/ (Full article)

 

Variability in diagnostic criteria for chronic fatigue syndrome may result in substantial differences in patterns of symptoms and disability

Abstract:

Chronic fatigue syndrome (CFS) is an illness that involves severe, prolonged exhaustion as well as neurologic, immunologic, and endocrine system pathology. Because the pathogenesis of CFS has yet to be determined, case definitions have relied on clinical observation in classifying signs and symptoms for diagnosis.

The current investigation examined differences between CFS as defined by Fukuda and colleagues and a set of criteria that has been stipulated for myalgic encephalomyelitis (ME). Dependent measures included psychiatric comorbidity, symptom frequency, symptom severity, and functional impairment. The ME and Fukuda et al. (1994) CFS criteria were compared with a group having chronic fatigue due to psychiatric reasons.

Significant differences occurred primarily with neurologic, neuropsychiatric, fatigue/weakness, and rheumatological symptoms. These findings suggest that it might be inappropriate to synthesize results from studies of this illness that use different definitions to select study populations.

 

Source: Jason LA, Helgerson J, Torres-Harding SR, Carrico AW, Taylor RR. Variability in diagnostic criteria for chronic fatigue syndrome may result in substantial differences in patterns of symptoms and disability. Eval Health Prof. 2003 Mar;26(1):3-22. http://www.ncbi.nlm.nih.gov/pubmed/12629919

 

Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome

Abstract:

The longitudinal course of subjective and objective neuropsychological functioning, psychological functioning, disability level, and employment status in chronic fatigue syndrome (CFS) was examined. The relations among several key outcomes at follow-up, as well as the baseline characteristics that predict change (e.g., improvement), were also evaluated.

The study sample consisted of 35 individuals who met the 1988 and 1994 CFS case definition criteria of the Centers for Disease Control (CDC) at intake. Participants were evaluated a mean of 41.9 (SEM = 1.7) months following their initial visit (range = 24-63 months).

Results indicated that objective and subjective attention abilities, mood, level of fatigue, and disability improve over time in individuals with CFS. Moreover, improvements in these areas were found to be interrelated at follow-up. Finally, psychiatric status, age, and between-test duration were significant predictors of outcome. Overall, the prognosis for CFS appears to be poor, as the majority of participants remained functionally impaired over time and were unemployed at follow-up, despite the noted improvements.

 

Source: Tiersky LA, DeLuca J, Hill N, Dhar SK, Johnson SK, Lange G, Rappolt G, Natelson BH. Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome. Appl Neuropsychol. 2001;8(1):41-50. http://www.ncbi.nlm.nih.gov/pubmed/11388123