Tag: cortisol

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

 

Neuroendocrine assessment of serotonin (5-HT) function in chronic fatigue syndrome

Abstract:

Prolactin and cortisol responses to dl-fenfluramine challenge were examined in 11 patients with chronic fatigue syndrome and in 11 healthy controls who were age and gender matched. After obtaining two baseline samples, each subject was given 60 mg of dl-fenfluramine orally and further blood samples were drawn hourly during the following five hours in order to measure prolactin and cortisol levels. There was no difference in either baseline or fenfluramine-induced hormonal responses between patients with chronic fatigue syndrome and controls. There was also no correlation between depression scores on HAM-D and hormonal responses in patients with chronic fatigue syndrome. The findings of this study do not support a role for 5-HT in chronic fatigue syndrome.

Comment in: Re: Endocrine responses to fenfluramine challenge in chronic fatigue syndrome. [Can J Psychiatry. 1996]

 

Source: Yatham LN, Morehouse RL, Chisholm BT, Haase DA, MacDonald DD, Marrie TJ. Neuroendocrine assessment of serotonin (5-HT) function in chronic fatigue syndrome. Can J Psychiatry. 1995 Mar;40(2):93-6. http://www.ncbi.nlm.nih.gov/pubmed/7788624

 

Neuroendocrine responses to d-fenfluramine and insulin-induced hypoglycemia in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disorder characterized by severe physical and mental fatigue and fatiguability of central rather than peripheral origin.

We hypothesized that CFS is mediated by changes in hypothalamopituitary function and so measured the adrenocorticotrophic hormone (ACTH), cortisol, growth hormone, and prolactin responses to insulin-induced hypoglycemia, and the ACTH, cortisol, and prolactin responses to serotoninergic stimulation with dexfenfluramine in nondepressed CFS patients and normal controls.

We have shown attenuated prolactin responses to hypoglycemia in CFS. There was also a greater ACTH response and higher peak ACTH concentrations (36.44 +/- 4.45 versus 25.60 +/- 2.78 pg ml), whereas cortisol responses did not differ, findings that are compatible with impaired adrenal cortical function.

This study provided evidence for both pituitary and adrenal cortical impairment in CFS and further studies are merited to both confirm and determine more precisely their neurobiological basis so that rational treatments can be evolved.

 

Source: Bearn J, Allain T, Coskeran P, Munro N, Butler J, McGregor A, Wessely S. Neuroendocrine responses to d-fenfluramine and insulin-induced hypoglycemia in chronic fatigue syndrome. Biol Psychiatry. 1995 Feb 15;37(4):245-52. http://www.ncbi.nlm.nih.gov/pubmed/7711161

 

Mild adrenocortical deficiency, chronic allergies, autoimmune disorders and the chronic fatigue syndrome: a continuation of the cortisone story

Abstract:

The possibility that patients with disorders that improve with administration of large, pharmacologic dosages of glucocorticoids, such as chronic allergies and autoimmune disorders, might have mild deficiency of cortisol production or utilization has received little attention.

Yet evidence that patients with rheumatoid arthritis improved with small, physiologic dosages of cortisol or cortisone acetate was reported over 25 years ago, and that patients with chronic allergic disorders or unexplained chronic fatigue also improved with administration of such small dosages was reported over 15 years ago, suggesting that these disorders might be associated with mild adrenocortical deficiency.

The apparent reasons for the failure of these reports to be confirmed or mentioned in medical textbooks and the facts needed to restore perspective are reviewed, and the need for further studies of the possible relationship of a mild deficiency of the production or utilization of cortisol and possibly other normal adrenocortical hormones to the development of these disorders is discussed.

 

Source: Jefferies WM. Mild adrenocortical deficiency, chronic allergies, autoimmune disorders and the chronic fatigue syndrome: a continuation of the cortisone story. Med Hypotheses. 1994 Mar;42(3):183-9. http://www.ncbi.nlm.nih.gov/pubmed/8057974

 

Outcome in the chronic fatigue syndrome

Comment on: Follow up of patients presenting with fatigue to an infectious diseases clinic. [BMJ. 1992]

 

EDITOR,-Michael Sharpe and colleagues’ follow up study of 177 patients with chronic fatigue of uncertain origin raises several important unanswered questions, which require further investigation. Factors such as a belief that their illness followed an infection, intolerance to alcohol, and membership of a support group for patients with myalgic encephalomyelitis were all associated with an adverse prognosis. Could it be that the authors had identified patients belonging to a distinct postinfectious subgroup as many doctors maintain they do? Clearly, if this is the case future studies of this nature will have to include more objective analysis of persisting viral infection (for example, analysis of muscle biopsy specimens with the polymerase chain reaction rather than tests for VP1 antigen); immune function (for example, function of natural killer cells rather than white cell counts); and hypothalamic-pituitary-axis activity (for example, up regulation of serotonin- I receptors and basal cortisol concentrations) to see if there are characteristic abnormalities that distinguish the postinfectious subgroup.

The high incidence of intolerance to alcohol is noted as intriguing, but from personal experience, as well as from seeing many patients with a classic postinfectious fatigue syndrome, I regard this observation as an important diagnostic feature. In these patients even small amounts of alcohol cause a further deterioration in cognitive function, and I suggest that a physiological explanation may lie in the fact that alcohol increases the concentration of the neurotransmitter y-aminobutyric acid, which in turn reduces the availability of calcium ions and hence depresses brain function still further.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883001/pdf/bmj00086-0047c.pdf

 

Source: Shepherd C. Outcome in the chronic fatigue syndrome. BMJ. 1992 Aug 8;305(6849):365. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883001/

 

Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is characterized by persistent or relapsing debilitating fatigue for at least 6 months in the absence of a medical diagnosis that would explain the clinical presentation. Because primary glucocorticoid deficiency states and affective disorders putatively associated with a deficiency of the arousal-producing neuropeptide CRH can be associated with similar symptoms, we report here a study of the functional integrity of the various components of the hypothalamic-pituitary-adrenal axis in patients meeting research case criteria for chronic fatigue syndrome.

Thirty patients and 72 normal volunteers were studied. Basal activity of the hypothalamic-pituitary-adrenal axis was estimated by determinations of 24-h urinary free cortisol-excretion, evening basal plasma total and free cortisol concentrations, and the cortisol binding globulin-binding capacity. The adrenal cortex was evaluated indirectly by cortisol responses during ovine CRH (oCRH) stimulation testing and directly by cortisol responses to graded submaximal doses of ACTH. Plasma ACTH and cortisol responses to oCRH were employed as a direct measure of the functional integrity of the pituitary corticotroph cell. Central CRH secretion was assessed by measuring its level in cerebrospinal fluid.

Compared to normal subjects, patients demonstrated significantly reduced basal evening glucocorticoid levels (89.0 +/- 8.7 vs. 148.4 +/- 20.3 nmol/L; P less than 0.01) and low 24-h urinary free cortisol excretion (122.7 +/- 8.9 vs. 203.1 +/- 10.7 nmol/24 h; P less than 0.0002), but elevated basal evening ACTH concentrations.

There was increased adrenocortical sensitivity to ACTH, but a reduced maximal response [F(3.26, 65.16) = 5.50; P = 0.0015). Patients showed attenuated net integrated ACTH responses to oCRH (128.0 +/- 26.4 vs. 225.4 +/- 34.5 pmol/L.min, P less than 0.04). Cerebrospinal fluid CRH levels in patients were no different from control values (8.4 +/- 0.6 vs. 7.7 +/- 0.5 pmol/L; P = NS).

Although we cannot definitively account for the etiology of the mild glucocorticoid deficiency seen in chronic fatigue syndrome patients, the enhanced adrenocortical sensitivity to exogenous ACTH and blunted ACTH responses to oCRH are incompatible with a primary adrenal insufficiency. A pituitary source is also unlikely, since basal evening plasma ACTH concentrations were elevated.

Hence, the data are most compatible with a mild central adrenal insufficiency secondary to either a deficiency of CRH or some other central stimulus to the pituitary-adrenal axis. Whether a mild glucocorticoid deficiency or a putative deficiency of an arousal-producing neuropeptide such as CRH is related to the clinical symptomatology of the chronic fatigue syndrome remains to be determined.

 

Source: Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi MJ, Chrousos GP, Gold PW. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab. 1991 Dec;73(6):1224-34. http://www.ncbi.nlm.nih.gov/pubmed/1659582