Tag: cortisol

The low dose ACTH test in chronic fatigue syndrome and in health

Abstract:

OBJECTIVE: A number of dynamic tests of the hypothalamic-pituitary-adrenal axis provide evidence for a mild central adrenal insufficiency inchronic fatigue syndrome (CFS). The 1 microgram adrenocorticotropin (ACTH) test has been proposed to be more sensitive than the standard 250 micrograms ACTH test in the detection of subtle pituitary-adrenal hypofunctioning. We aimed to establish whether the 1 microgram ACTH test would support such a dysregulation in CFS, and also, given the relative novelty of this test in clinical practice and the uncertainty with regard to appropriate cut-off values for normality, to compare our healthy volunteer data with those of previous studies.

PATIENTS AND DESIGN: Twenty subjects with CFS, diagnosed according to Centres for Disease Control and Prevention criteria, were compared with 20 healthy volunteer subjects. All participants underwent a 1 microgram ACTH test beginning at 1400 h. Plasma samples for cortisol estimation were drawn at 0, +30 and +40 min.

RESULTS: Baseline cortisol values did not differ between CFS patients and healthy subjects. The delta cortisol (maximum increment from baseline) value was significantly lower in the CFS than the volunteer group (P < 0.05). Comparison of the +30 min cortisol values revealed no significant differences. Using an incremental cortisol of > 250 nmol/l as an arbitrary cutoff point, two (10%) of the healthy subjects and nine (45%) of the CFS subjects failed the test on this basis (chi 2 = 4.3, df = 38, P < 0.05).

CONCLUSIONS: This study provides further evidence for a subtle pituitary-adrenal insufficiency in subjects with chronic fatigue syndrome compared to healthy volunteers. Disparities between our healthy volunteer data and those of other groups using the 1 microgram ACTH test suggest that the test may not be as reliable as previously indicated.

Comment in: The 1microg Synacthen test in chronic fatigue syndrome. [Clin Endocrinol (Oxf). 2000]

 

Source: Scott LV, Medbak S, Dinan TG. The low dose ACTH test in chronic fatigue syndrome and in health. Clin Endocrinol (Oxf). 1998 Jun;48(6):733-7. http://www.ncbi.nlm.nih.gov/pubmed/9713562

 

Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome

Abstract:

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase.

Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion.

For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls.

In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively).

These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

 

Source: Cannon JG, Angel JB, Abad LW, O’Grady J, Lundgren N, Fagioli L, Komaroff AL. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. J Clin Immunol. 1998 Jul;18(4):291-8. http://www.ncbi.nlm.nih.gov/pubmed/9710746

 

Naloxone-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome

Abstract:

BACKGROUND: Opioidergic pathways have an inhibitory regulatory influence on the hypothalamic-pituitary-adrenal axis (HPA) in man. Previous studies have suggested impairment of pituitary-adrenal activation in chronic fatigue syndrome (CFS). We, therefore, decided to investigate the extent of opioid inhibition of HPA activity in CFS as a possible explanation for the reputed HPA hypofunctioning in patients with CFS.

METHOD: Thirteen patients with CFS, diagnosed according to CDC criteria, were compared with thirteen healthy subjects. Adrenocorticotropin (ACTH) and cortisol (CORT) responses were measured following the administration of the opiate antagonist naloxone.

RESULTS: Baseline ACTH and cortisol levels did not differ between the two groups. The release of ACTH (but not cortisol) was significantly blunted in the CFS subjects compared with controls.

CONCLUSIONS: Naloxone mediated activation of the HPA is attenuated in CFS. Excessive opioid inhibition of the HPA is thus an unlikely explanation for the HPA dysregulation in this disorder.

 

Source: Scott LV, Burnett F, Medbak S, Dinan TG. Naloxone-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome. Psychol Med. 1998 Mar;28(2):285-93. http://www.ncbi.nlm.nih.gov/pubmed/9572086

 

Core body temperature is normal in chronic fatigue syndrome

Abstract:

BACKGROUND: Subjects with chronic fatigue syndrome (CFS) frequently report symptoms of subnormal body temperature and low-grade fever. We conducted a study to determine whether CFS subjects manifest any abnormality of core body temperature (CBT) that might help explain their fatigue.

METHODS: Continuous 24-hour recordings of CBT measured every 5 min were performed in 7 subjects meeting the Centers for Disease Control definition of CFS. Three additional groups were studied: normal controls, subjects with seasonal allergy, and subjects with major depression. Subjects (n = 7) in each group were age-, sex-, and weight-matched to the CFS group and had normal basal metabolic rates, thyroid function, and 24-hour urinary free cortisol excretions. CBT was measured with an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. Each pill was factory-calibrated to +/- 0.1 degree C and field-calibrated with a water bath calibration prior to use.

RESULTS: The 24-hour mean calibration-adjusted CBTs of each group were not significantly different (control: 37.00 +/- 0.17 degrees C; CFS: 37.04 +/- 0.31 degrees C; allergy: 37.15 +/- 0.18 degrees C; depression: 37.16 +/- 0.18 degrees C). Similarly, the mean peak and trough circadian temperatures were not statistically different. The mean 24-hour profile of CBT for each group showed a similar circadian rhythm. In simultaneously collected blood samples, each group showed a similar circadian profile of serum cortisol with a peak occurring at 08:00.

CONCLUSIONS: Subjects with CFS have normal CBT despite frequent self-reports of subnormal body temperature and low-grade fever.

 

Source: Hamilos DL, Nutter D, Gershtenson J, Redmond DP, Clementi JD, Schmaling KB, Make BJ, Jones JF. Core body temperature is normal in chronic fatigue syndrome. Biol Psychiatry. 1998 Feb 15;43(4):293-302. http://www.ncbi.nlm.nih.gov/pubmed/9513740

 

Basal activity of the hypothalamic-pituitary-adrenal axis in patients with the chronic fatigue syndrome (neurasthenia)

Abstract:

BACKGROUND: Impairments in both basal activity and activation of the hypothalamic-pituitary- adrenal axis (HPA) have been reported in chronic fatigue syndrome (CFS; neurasthenia). We sought to replicate these findings and examined basal activity of the HPA in a carefully selected sample of patients with CFS.

METHODS: Basal activity of the HPA was assessed using salivary and urinary cortisol collection over a 24-hour period in 22 (12 male; 10 female) patients meeting criteria for CFS and appropriate controls.

RESULTS: Salivary and urinary cortisol measures did not differ between CFS patients and controls.

CONCLUSIONS: Basal activity of the HPA was not reduced in CFS patients. Reasons for the failure to replicate previous findings are discussed.

 

Source: Young AH, Sharpe M, Clements A, Dowling B, Hawton KE, Cowen PJ. Basal activity of the hypothalamic-pituitary-adrenal axis in patients with the chronic fatigue syndrome (neurasthenia). Biol Psychiatry. 1998 Feb 1;43(3):236-7. http://www.ncbi.nlm.nih.gov/pubmed/9494707

 

A comparison of salivary cortisol in chronic fatigue syndrome, community depression and healthy controls

Abstract:

BACKGROUND: Previous studies reporting cortisol hyposecretion in chronic fatigue syndrome may have been confounded by venepuncture, fasting and hospitalisation.

METHODS: Morning and evening salivary cortisol were obtained on consecutive days in the first 3 days of the menstrual cycle and compared in three samples of women taking no medication and matched for age: 14 patients with chronic fatigue syndrome, 26 community cases of ICD-10 current depressive episodes and 131 healthy community controls.

RESULTS: The mean evening cortisol was significantly lower in the chronic fatigue syndrome patients compared to controls with depression (P = 0.02) and healthy controls (P = 0.005). Chronic fatigue syndrome patients without psychiatric disorder had significantly lower morning salivary cortisols compared to controls (P = 0.009).

CONCLUSION: Chronic fatigue syndrome patients display cortisol hyposecretion in saliva as well as plasma compared to patients with depression and healthy controls.

LIMITATIONS: Small samples of female patients with cortisol estimated at only two time points in the day. Cortisol secretion may be secondary to other neurotransmitter abnormalities or other physiological or lifestyle factors in chronic fatigue syndrome patients.

CLINICAL RELEVANCE: Chronic fatigue syndrome is biochemically distinct from community depression.

 

Source: Strickland P, Morriss R, Wearden A, Deakin B. A comparison of salivary cortisol in chronic fatigue syndrome, community depression and healthy controls. J Affect Disord. 1998 Jan;47(1-3):191-4. http://www.ncbi.nlm.nih.gov/pubmed/9476760

 

Urinary free cortisol excretion in chronic fatigue syndrome, major depression and in healthy volunteers

Abstract:

Urinary free cortisol excretion (UFC) was compared in 21 patients with chronic fatigue syndrome (CFS), in 10 melancholic depressives and in 15 healthy controls.

Patients with depression had UFC values which were significantly higher than healthy comparison subjects, whereas UFC excretion of CFS patients was significantly lower than the comparison group.

These findings are in keeping with currently held hypotheses of hyperactivity and hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis in depression and chronic fatigue syndrome respectively. Five of the 21 CFS patients had a co-morbid depressive illness. This sub-group retained the profile of UFC excretion of those with CFS alone, suggesting a different pathophysiological basis for depressive symptoms in CFS.

 

Source: Scott LV, Dinan TG. Urinary free cortisol excretion in chronic fatigue syndrome, major depression and in healthy volunteers. J Affect Disord. 1998 Jan;47(1-3):49-54. http://www.ncbi.nlm.nih.gov/pubmed/9476743

 

Salivary cortisol profiles in chronic fatigue syndrome

Abstract:

Salivary cortisol profiles (hourly sampling over a 16-hour period) of 10 patients with chronic fatigue syndrome (CFS) but without concurrent depressive disorder were compared with those of 10 healthy volunteers matched for age, sex and menstrual cycle. The mean saliva cortisol concentration over the 16-hour period was slightly but significantly greater in the patients than the controls (p < 0.05). These findings are at variance with earlier reports that CFS is a hypocortisolaemic state and suggest that in CFS the symptom of fatigue is not caused by hypocortisolaemia.

 

Source: Wood B, Wessely S, Papadopoulos A, Poon L, Checkley S. Salivary cortisol profiles in chronic fatigue syndrome. Neuropsychobiology. 1998;37(1):1-4. http://www.ncbi.nlm.nih.gov/pubmed/9438265

 

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient

Abstract:

A series of publications from our laboratory have indicated that the practice of megadose vitamin C drip infusion treatment enhanced the activity of endogenous glucocorticoids in such a way as to improve the clinical course of allergy and autoimmune disease-a disease entity that is known to respond to the therapeutic effect of glucocorticoids. The present paper represents an extention of our vitamin C studies, and intends to investigate the problem whether or not chronic fatigue syndrome (CFS), an acquired immunodeficiency disease, can also be counted as one of the candidate diseases for the vitamin C infusion treatment.

We prepared two kinds of vitamin C infusion sets for the clinical use: the dehydroepiandrosterone-annexed vitamin C infusion set (the new set) and the annex-free vitamin C infusion set (the old set). The new set was expected to enhance the endogenous activities of both glucocorticoids and gonadal steroids.

We followed the clinical course of a male CFS patient using the old and new vitamin C infusion sets, and with and without the oral intake of erythromycin and chloramphenico. Results obtained are as follows:

a) the observation period of a study subject covered a period of August 1995 to May 1996. Combination of pneumonia signs and dermatomyositis signs marked the onset of his CFS.

b) Old infusion treatment together with the short term antibiotics treatment was found effective for the control of pneumonia in the first stage of the disease (from August to October, 1995).

c) Signs of pneumonia recurrence gradually became eminent in the second stage of disease (from November, 1995, to January, 1996) in spite of the moderate frequency of the old treatment together with stepwise prolongation of the antibiotics treatment.

d) The alternate practice of the old and new infusion treatments together with the long-term antibiotics treatment, as conducted in the 3rd stage of disease (from February to May, 1996) led to substantial extinction of pneumonia signs (leucocytosis, tachycardia etc).

e) The practice of the new infusion treatment markedly increased the excretion of both 17-ketosteroids and 17-hydroxycorticosteroids in the urine. Evidence was also available to indicate that the dehydroepiandrosterone annex was converted to testosterone, which in turn made a contribution to the control of CFS.

f) The immunological survey of lymphocyte subsets including NK cell percent failed to find a coherent change in a study subject with CFS.

In conclusion, the above results could be taken as evidence to indicate that the new vitamin C infusion treatment effectuates the clinical control of CFS by fortifying the endogenous activities of both cortisol and testosterone. The significance of parallelism between pulmonary infection and CFS, as observed in the clinical course of the test subject, was discussed in the light of the focal infection theory of nephritis.

 

Source: Kodama M, Kodama T, Murakami M. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient. In Vivo. 1996 Nov-Dec;10(6):575-84. http://www.ncbi.nlm.nih.gov/pubmed/8986467

 

Short-term night-shift working mimics the pituitary-adrenocortical dysfunction in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether a short period (5 days) of night-shift work affected the pituitary-adrenal responses to CRH. Ten nurses (8 female and 2 male; age 28.1 +/- 1.7 yr: mean +/- SEM) working at the Royal Liverpool University Hospital, and who regularly undertook periods of night and day shift work were enrolled.

Measurements were made of basal ACTH and cortisol concentrations, and their responses to iv ovine CRH (1 microgram.kg-1). Basal ACTH concentrations were higher during the night shift than during the day shift (12.9 +/- 5.1 pmol.L-1 vs. 4.7 +/- 1.2 pmol.L-1, P < 0.01) whereas cortisol concentrations were lower (551 +/- 48 nmol.L – 1 vs. 871 +/- 132 nmol.L – 1, P < 0.01). After CRH injection, ACTH concentrations remained consistently higher during the night shift, but the integrated increase in ACTH concentration was lower (P < 0.05) than during the day shift. Conversely, the increase in cortisol concentration was greater during the night shift than the day shift (283 +/- 53 nmol.L-1 vs. 134 +/- 41 nmol.L-1, P < 0.05).

We conclude that the pituitary-adrenal responses to CRH are markedly disrupted after only 5 days of nighttime work. These abnormalities mimic those previously observed in patients with chronic fatigue syndrome. Neuroendocrine abnormalities reported to be characteristic of chronic fatigue syndrome may be merely the consequence of disrupted sleep and social routine.

 

Source: Leese G, Chattington P, Fraser W, Vora J, Edwards R, Williams G. Short-term night-shift working mimics the pituitary-adrenocortical dysfunction in chronic fatigue syndrome. J Clin Endocrinol Metab. 1996 May;81(5):1867-70. http://www.ncbi.nlm.nih.gov/pubmed/8626849