Category: Treatment

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

 

Midodrine treatment for chronic fatigue syndrome

Abstract:

The long term results of midodrine treatment in a patient having debilitating chronic fatigue syndrome (CFS) are reported. Midodrine treatment, directed at the autonomic nervous system, resulted in correction of the dysautonomia followed by improvement of fatigue. This finding is consistent with the hypothesis that dysautonomia plays a major part in the pathophysiology of CFS and that therapies directed at the autonomic nervous system may be effective in the treatment of CFS.

 

Source: Naschitz J, Dreyfuss D, Yeshurun D, Rosner I. Midodrine treatment for chronic fatigue syndrome. Postgrad Med J. 2004 Apr;80(942):230-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742969/pdf/v080p00230.pdf (Full article)

 

The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of chronic fatigue syndrome patients–a pilot study

Abstract:

OBJECTIVE: To explore the effect of granisetron, a 5-HT3 antagonist, on fatigue and functional impairment in patients with chronic fatigue syndrome (CFS).

METHODS: Five female patients were eligible to receive oral granisetron for one month (1 mg a day for the first two weeks and 2 mg a day for the second two weeks). The patients had to be between 18 and 65 years of age and suffering from CFS according to the CDC criteria. The effect was assessed by pre- and post-testing, using validated instruments designed to assess the different dimensions of CFS. Treatment response was also evaluated by visual analogue scales (VAS) for fatigue. Analysis was based on intention to treat.

RESULTS: Treatment with granisetron resulted in significant improvement in fatigue severity and functional impairment. Activity level showed no significant increase.

CONCLUSION: The promising results of this study have encouraged us to perform a placebo-controlled, double-blind study to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

Comment in: Pilot studies: one swallow does not make a summer… [Neth J Med. 2003]

 

Source: The GK, Prins J, Bleijenberg G, van der Meer JW. The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of chronic fatigue syndrome patients–a pilot study.  Neth J Med. 2003 Sep;61(9):285-9. http://www.njmonline.nl/getpdf.php?id=16 (Full article)

 

Pilot studies: one swallow does not make a summer…

Abstract:

What should we expect from pilot studies, done in small series of patients? In the literature there are many examples of small studies with very promising results, that in subsequent larger or better controlled studies proved to be much less promising, or even disastrous. In some instances the initial favourable outcome was due to selection bias. In others the use of nonvalidated methods of measuring outcome made the reproducibility of promising observations problematic. However, we have to start somewhere. In ths issue The et al. report favourable results of granisetron treatment in four out of five patients with chronic fatigue syndrome. A prospective, randomised, placebo-controlled, double-blind clinical trial with granisetron in patients with chronic fatigue syndrome is now ongoing.

Comment on: The effect of granisetron, a 5-HT3 receptor antagonist, in the treatment of chronic fatigue syndrome patients–a pilot study. [Neth J Med. 2003]

 

Source: van Gelder T, Smits P. Pilot studies: one swallow does not make a summer… Neth J Med. 2003 Sep;61(9):270-2. http://www.njmonline.nl/getpdf.php?id=13 (Full article)

 

Medication use by persons with chronic fatigue syndrome: results of a randomized telephone survey in Wichita, Kansas

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities, and a characteristic symptom complex. Patients use a variety of prescribed and self-administered medications, vitamins, and supplements for relief of their symptoms. The objective of this study was to describe utilization of medications and supplements by persons with CFS and non-fatigued individuals representative of the general population of Wichita, Kansas.

METHODS: We used a random-digit dialing telephone survey to identify persons with CFS in the general population of Wichita, Kansas. Subjects who on the basis of telephone interview met the CFS case definition, and randomly selected non-fatigued controls, were invited for a clinic evaluation that included self-reported use of medications and supplements. Sex-adjusted odds ratios and 95% confidence interval were estimated to measure the association between CFS and use of various drug categories.

RESULTS: We clinically evaluated and classified 90 subjects as CFS during the study and also collected clinical data on 63 who never described fatigue. Subjects with CFS reported using 316 different drugs compared to 157 reported by non-fatigued controls. CFS subjects were more likely to use any drug category than controls (p = 0.0009). Pain relievers and vitamins/supplements were the two most common agents listed by both groups. In addition CFS persons were more likely to use pain relievers, hormones, antidepressants, benzodiazepines, gastro-intestinal, and central nervous system medications (Sex-adjusted odds ratios range = 2.97 – 12.78).

CONCLUSION: Although the reasons for increased use of these agents were not elucidated, the data indicated the CFS patients’ need for symptom relief.

 

Source: Jones JF, Nisenbaum R, Reeves WC. Medication use by persons with chronic fatigue syndrome: results of a randomized telephone survey in Wichita, Kansas. Health Qual Life Outcomes. 2003 Dec 2;1:74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC293479/ (Full article)

 

Chronic fatigue syndrome. The patient centred clinical method–a guide for the perplexed

Abstract:

BACKGROUND: Chronic fatigue states are common in general practice and over the past 20 years there has been considerable worldwide consensus developed on the criteria for chronic fatigue syndrome (CFS) also commonly known as myalgic encephalomyelitis (ME). Chronic fatigue syndrome is an illness characterised by the new onset of disabling fatigue, accompanied by cognitive, musculoskeletal and sleep symptoms. There are no specific diagnostic tests or biological markers and the diagnosis is made by ruling out other causes of fatigue. The pathophysiology of CFS is still unclear.

OBJECTIVE: This article discusses the application of the patient centred clinical method to the diagnosis and treatment of CFS.

DISCUSSION: There is no new breakthrough in the diagnosis or management of CFS in spite of much research and controversy. There is considerable evidence that the best place to manage CFS is in primary care under the care of the patient’s own general practitioner, but it has been suggested that doctors feel unable to deal with the problem. The patient centred clinical method offers a constructive guide to management. The author considers that the best hope for sufferers is self management guided by a supportive and helpful health professional, preferably the patient’s own GP.

 

Source: Murdoch JC. Chronic fatigue syndrome. The patient centred clinical method–a guide for the perplexed. Aust Fam Physician. 2003 Nov;32(11):883-7. http://www.ncbi.nlm.nih.gov/pubmed/14650782

 

The head-up tilt test in the diagnosis and management of chronic fatigue syndrome

Fatigue, as a symptom, refers to a sense of lethargy or loss of energy. Fatigue is common in infections, endocrine disorders, heart failure, chronic diseases of the lungs, liver or kidneys, malignancies, anemia, nutritional deficits, inflammatory arthritis, Parkinson’s disease, depression, anxiety states, effect of certain medications, or drug withdrawal [1]. Population-based studies show that fatigue is one of the most common somatic symptoms, with as much as 20± 30% of the population complaining of chronic fatigue [2]. Only a small fraction of these satisfy the clinical definition criteria for chronic fatigue syndrome [1].

You can read the rest of this article here: https://www.ima.org.il/FilesUpload/IMAJ/0/54/27402.pdf

 

Source: Naschitz JE, Sabo E, Dreyfuss D, Yeshurun D, Rosner I. The head-up tilt test in the diagnosis and management of chronic fatigue syndrome. Isr Med Assoc J. 2003 Nov;5(11):807-11. https://www.ima.org.il/FilesUpload/IMAJ/0/54/27402.pdf (Full article)

 

Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome

Abstract:

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.

 

Source: Kerr JR, Cunniffe VS, Kelleher P, Bernstein RM, Bruce IN.  Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome. Clin Infect Dis. 2003 May 1;36(9):e100-6. Epub 2003 Apr 22. http://cid.oxfordjournals.org/content/36/9/e100.long (Full article)

 

Use of IVIG in secondary immunodeficiencies

Abstract:

The research connects usefulness of intravenous preparates of immunoglobulins in patients with secondary immunodeficiencies. Basing on the data of literature there was discussed the using IVIG in patients with HIV infection and with the chronic fatigue syndrome. There was also discussed the matter of using IVIG after multiorgans traumas, burns and operations with high risk complications.

 

Source: Zeman K, Lewandowicz-Uszyńska A. Use of IVIG in secondary immunodeficiencies. Postepy Hig Med Dosw. 2002;56 Suppl:91-102. [Article in Polish] http://www.ncbi.nlm.nih.gov/pubmed/12661419

 

 

Chronic unexplained fatigue

Comment on: Chronic unexplained fatigue. [Postgrad Med J. 2002]

 

I found the editorial on chronic fatigue syndrome by White both surprising and disappointing, because he used the title “Chronic unexplained fatigue” and the subtitle “A riddle wrapped in a mystery inside an enigma”, but his editorial, by ignoring very important facts about chronic fatigue syndrome, actually perpetuates that riddle, rather than helping to solve it.

If a puzzling and poorly manageable condition shares more than 40 features, including all of its diagnostic criteria, with a well known and easily treatable disease, this astounding clinical overlap should not be ignored, because reason not only suggests that the mysterious illness may simply be a form of the well known disease, but also hints that it is worthwhile assessing whether the classic therapy for that treatable disease could be effective for the enigmatic condition as well.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757928/pdf/v078p00763a.pdf

 

Source: Baschetti R. Chronic unexplained fatigue. Postgrad Med J. 2002 Dec;78(926):763; author reply 763. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757928/pdf/v078p00763a.pdf