Tag: Cleare

Integrity of the growth hormone/insulin-like growth factor system is maintained in patients with chronic fatigue syndrome

Abstract:

GH deficiency states and chronic fatigue syndrome (CFS) share several characteristics, and preliminary studies have revealed aspects of GH dysfunction in CFS.

This study assessed indexes of GH function in 37 medication-free CFS patients without comorbid psychiatric illness and 37 matched healthy controls. We also assessed GH function before and after treatment with low dose hydrocortisone, which has been shown recently to reduce fatigue in CFS. We measured basal levels of serum insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2 and IGFBP-3 together with 24-h urinary GH excretion. We also performed 2 dynamic tests of GH function: a 100-microg GHRH test and an insulin stress test using 0.15 U/kg BW insulin.

There were no differences between patients and controls in basal levels of IGF/IGFBP or in urinary GH excretion. GH responses to both the GHRH test and the insulin stress test were no different in patients and controls.

CFS patients did have a marginally reduced suppression of IGFBP-1 during the insulin stress test. Hydrocortisone treatment had no significant effect on any of these parameters. There is no evidence of GH deficiency in CFS. At the doses used, hydrocortisone treatment appears to have little impact on GH function.

 

Source: Cleare AJ, Sookdeo SS, Jones J, O’Keane V, Miell JP. Integrity of the growth hormone/insulin-like growth factor system is maintained in patients with chronic fatigue syndrome. J Clin Endocrinol Metab. 2000 Apr;85(4):1433-9. http://www.ncbi.nlm.nih.gov/pubmed/10770178

 

Chronic fatigue syndrome

Definition: Chronic fatigue syndrome is characterised by severe, disabling fatigue and other symptoms, including musculoskeletal pain, sleep disturbance, impaired concentration, and headaches. Two widely used definitions of chronic fatigue syndrome (from the US Centers for Disease Control and Prevention 1 and from Oxford 2—see table) were developed as operational criteria for research. There are two important differences between these definitions. The British criteria insist on the presence of mental fatigue; the American criteria include a requirement for several physical symptoms, reflecting the belief that chronic fatigue syndrome has an underlying immunological or infective pathology.

Incidence/prevalence: Community and primary care based studies have reported the prevalence of chronic fatigue syndrome to be 0.2-2.6%, depending on the criteria used.3 4 Systematic population surveys have found similar rates of the syndrome in people of different socioeconomic status, and in all ethnic groups.4 5 Female sex is the only demographic risk factor (relative risk 1.3 to 1.7 depending on diagnostic criteria used).6

Aetiology: The cause of chronic fatigue syndrome is poorly understood.

Prognosis: Studies of prognosis in chronic fatigue syndrome have focused on people attending specialist clinics, who are likely to have had the condition for longer and to have a poorer outlook. Children with the syndrome seem to have a notably better outcome: 54-94% of children show definite improvement (after up to six years’ follow up); 20-50% of adults show some improvement in the medium term and only 6% return to premorbid levels of functioning.7 Despite the considerable burden of morbidity associated with chronic fatigue syndrome, there is no evidence of increased mortality. Outcome is influenced by the presence of psychiatric disorders and beliefs about causation and treatment.7

Aims: To reduce levels of fatigue and associated symptoms; to increase levels of activity; to improve quality of life.

Outcomes: Severity of symptoms; effects on physical function and quality of life measured in several different ways by: the medical outcomes survey short form general health survey (SF-36), a rating scale measuring limitation of physical functioning caused by ill health 8; the Karnofsky scale, a modified questionnaire originally developed for the rating of quality of life in people undergoing chemotherapy for malignancy 9; the Beck depression inventory 10; the sickness impact profile, a measure of the influence of symptoms on social and physical functioning 11; and self reported severity of symptoms and levels of activity.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1117488/

 

Source: Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue syndrome. BMJ : British Medical Journal. 2000;320(7230):292-296. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1117488/ (Full article)

 

Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial

Abstract:

BACKGROUND: Reports of mild hypocortisolism in chronic fatigue syndrome led us to postulate that low-dose hydrocortisone therapy may be an effective treatment.

METHODS: In a randomised crossover trial, we screened 218 patients with chronic fatigue. 32 patients met our strict criteria for chronic fatigue syndrome without co-morbid psychiatric disorder. The eligible patients received consecutive treatment with low-dose hydrocortisone (5 mg or 10 mg daily) for 1 month and placebo for 1 month; the order of treatment was randomly assigned. Analysis was by intention to treat.

FINDINGS: None of the patients dropped out. Compared with the baseline self-reported fatigue scores (mean 25.1 points), the score fell by 7.2 points for patients on hydrocortisone and by 3.3 points for those on placebo (paired difference in mean scores 4.5 points [95% CI 1.2-7.7], p=0.009). In nine (28%) of the 32 patients on hydrocortisone, fatigue scores reached a predefined cut-off value similar to the normal population score, compared with three (9%) of the 32 on placebo (Fisher’s exact test p=0.05). The degree of disability was reduced with hydrocortisone treatment, but not with placebo. Insulin stress tests showed that endogenous adrenal function was not suppressed by hydrocortisone. Minor side-effects were reported by three patients after hydrocortisone treatment and by one patient after placebo.

INTERPRETATION: In some patients with chronic fatigue syndrome, low-dose hydrocortisone reduces fatigue levels in the short term. Treatment for a longer time and follow-up studies are needed to find out whether this effect could be clinically useful.

Comment in:

Hydrocortisone and chronic fatigue syndrome. [Lancet. 1999]

Hydrocortisone and chronic fatigue syndrome. [Lancet. 1999]

Chronic fatigue syndrome and functional hypoadrenia–fighting vainly the old ennui. [Lancet. 1999]

Hydrocortisone and chronic fatigue syndrome. [Lancet. 1999]

Hydrocortisone and chronic fatigue syndrome. [Lancet. 1999]

 

Source: Cleare AJ, Heap E, Malhi GS, Wessely S, O’Keane V, Miell J. Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet. 1999 Feb 6;353(9151):455-8. http://www.ncbi.nlm.nih.gov/pubmed/9989716

 

Contrasting neuroendocrine responses in depression and chronic fatigue syndrome

Abstract:

Hypothalamic-pituitary-adrenal (HPA) axis and central 5-HT function were compared in chronic fatigue syndrome (CFS), depression and healthy states. 10 patients with CFS and 15 patients with major depression were matched for age, weight, sex and menstrual cycle with 25 healthy controls.

Baseline-circulating cortisol levels were highest in the depressed, lowest in the CFS and intermediate between the two in the control group (P = 0.01). Prolactin responses to the selective 5-HT-releasing agent d-fenfluramine were lowest in the depressed, highest in the CFS and intermediate between both in the healthy group (P = 0.01). Matched pair analysis confirmed higher prolactin responses in CFS patients than controls (P = 0.05) and lower responses in depressed patients than controls (P = 0.003). There were strong inverse correlations between prolactin and cortisol responses and baseline cortisol values.

These data confirm that depression is associated with hypercotisolaemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolaemia and increased 5-HT function. The opposing responses in CFS and depression may be related to reversed patterns of behavioural dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders.

 

Source: Cleare AJ, Bearn J, Allain T, McGregor A, Wessely S, Murray RM, O’Keane V. Contrasting neuroendocrine responses in depression and chronic fatigue syndrome. J Affect Disord. 1995 Aug 18;34(4):283-9. http://www.ncbi.nlm.nih.gov/pubmed/8550954