Tag: HPA axis

Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health

Abstract:

BACKGROUND: Hyperactivity and hypoactivity of the HPA have been forwarded as of pathophysiological relevance in major depressive disorder and chronic fatigue syndrome (CFS), respectively.

METHODS: This study examines cortisol levels in the two disorders, and also assesses levels of the adrenal androgens, dehydroepiandrosterone (DHEA) and its sulphate derivative (DHEA-S), and 17-alpha-hydroxyprogesterone; 15 subjects with CFS diagnosed according to CDC criteria, 15 subjects with DSM III-R major depression and 11 healthy subjects were compared.

RESULTS: DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group; DHEA-S levels, but not DHEA, were lower in the depressives; cortisol and 17-alpha-hydroxyprogesterone did not differ between the three groups.

CONCLUSIONS: A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested.

 

Source: Scott LV, Salahuddin F, Cooney J, Svec F, Dinan TG. Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health. J Affect Disord. 1999 Jul;54(1-2):129-37. http://www.ncbi.nlm.nih.gov/pubmed/10403156

 

Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers

Abstract:

BACKGROUND: Corticotropin-releasing hormone (CRH) and vasopressin (VP) are the two principal neuropeptide regulators of the hypothalamic-pituitary-adrenal axis in man, with VP serving to augment CRH-induced adrenocorticotropic hormone (ACTH) release. Unlike VP, desmopressin (DDAVP), which is a synthetic analogue of VP, when administered alone, has not been shown in healthy subjects to have consistent ACTH-releasing properties. It has been suggested that chronic fatigue syndrome (CFS), characterized by profound fatigue and a constellation of other symptoms, may be caused by a central deficiency of CRH.

METHODS: We administered 100 micrograms ovine CRH (oCRH) and 10 micrograms DDAVP, both alone and in combination, to a group of subjects with CFS, and to a group of healthy volunteers. Our aim was to establish the effect of DDAVP on CRH-induced ACTH release in these two groups.

RESULTS: The delta-ACTH responses to oCRH were attenuated in the CFS (21.0 +/- 4.5 ng/L) compared to the control subjects (57.8 +/- 11.0 ng/L; t = 3.2, df = 21, p < .005). The delta-cortisol responses were also reduced in the CFS (157.6 +/- 40.7 nmol/L) compared to the healthy subjects (303.5 +/- 20.9 nmol/L; t = 3.1, df = 21, p < .01). The delta-ACTH and delta-cortisol responses to DDAVP alone did not differ between the two groups. On administration of both CRH and DDAVP no response differences between the two groups for either ACTH (p = .3) or cortisol output (p = .87) were established. Comparing the ACTH and cortisol responses to CRH and CRH/DDAVP in only those individuals from each group who had both tests, the cortisol output to the combination was significantly greater in the CFS compared to the healthy group. The ACTH output was also increased in the former group, though this was not significant.

CONCLUSIONS: DDAVP augments CRH-mediated pituitary-adrenal responsivity in healthy subjects and in patients with CFS. That DDAVP was capable of normalizing the pituitary-adrenal response to oCRH in the CFS group suggests there may be increased vasopressinergic responsivity of the anterior pituitary in CFS and/or that DDAVP may be exerting an effect at an adrenal level.

 

Source: Scott LV, Medbak S, Dinan TG. Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers. Biol Psychiatry. 1999 Jun 1;45(11):1447-54. http://www.ncbi.nlm.nih.gov/pubmed/10356627

 

A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) frequently associate the disease onset with a period of high physical and/or emotional stress. Alterations in hypothalamic-pituitary adrenal axis (HPA) function have been demonstrated. Although Cortisol production in patients with CFS has proven to be low, Dehydroepiandrosterone (DHEA) production has not been measured. DHEA output may be altered in this population.

The purpose of this uncontrolled, prospective, 6 month study of 23 white women, ages 35-55 was to identify CFS patients with suboptimal serum levels of DHEA-sulphate (DHEA-S), defined as DHEA-S <2.0 microg/mL, and to treat those patients with oral DHEA.

DHEA-S levels were re-measured after 4-6 weeks of oral DHEA therapy (25 mg). If DHEA-S remained <2.0 microg/ mL, or if no clinical response was achieved after 4-6 weeks of therapy, then an increased dose of DHEA was given. Physical and psychological impairment and disability status were measured by the MHAQII before DHEA intervention and at 3-month intervals. Of initially screened patients with CFS, 76% (116 of 153) were ages 35-55, and 89% (103 of 116) had suboptimal (<2.0 microg/mL) production of DHEA-S.

Supplementation with DHEA to CFS patients lead to a significant reduction in the symptoms of CFS: pain (improved by 18%, p = 0.035), fatigue (decreased by 21%, p = 0.009)), activities of daily living (improved by 8.5%, p = 0.058), helplessness (decreased by 11%, p = 0.015), anxiety (decreased by 35%, p < 0.01), thinking (improved by 26%, p < 0.01), memory (improved by 17%, p < 0.05), and sexual problems (improved by 22%, p = 0.06) over the period of the trial.

Further study is necessary to determine the safety and efficacy of supplementation of DHEA to this population in a controlled setting.

 

Source: Himmel PB, Seligman TM. A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome. J Clin Rheumatol. 1999 Apr;5(2):56-9. http://www.ncbi.nlm.nih.gov/pubmed/19078357

 

The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome

Abstract:

HPA axis abnormalities in FM, CFS, and other stress-related disorders must be placed in a broad clinical context. We know that interventions providing symptomatic improvement in patients with FM and CFS can directly or indirectly affect the HPA axis. These interventions include exercise, tricyclic anti-depressants, and serotonin reuptake inhibitors. There is little direct information as to how the specific HPA axis perturbations seen in FM can be related to the major symptomatic manifestations of pain, fatigue, sleep disturbance, and psychological distress. Since many of these somatic and psychological symptoms are present in other syndromes that exhibit HPA axis disturbances, it seems reasonable to suggest that there may be some relationship between basal and dynamic function of the HPA axis and clinical manifestations of FM and CFS.

 

Source: Crofford LJ. The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome. Z Rheumatol. 1998;57 Suppl 2:67-71. http://www.ncbi.nlm.nih.gov/pubmed/10025087

 

Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome (CFS) is a condition of unknown etiology, characterized by a persistent debilitating fatigue, the muscle-related symptoms and the neuropsychiatric symptoms.

Recently, it has been reported that the patients with CFS might have impaired activation of the hypothalamic-pituitary-adrenal axis, and suggested that a part of the patho-genesis of CFS might be associated with abnormalities of the endocrine system.

Herein, we show that the majority of Japanese patients with CFS had a serum dehydroepiandrosterone sulfate (DHEA-S) deficiency. Serum DHEA-S is one of the most abundantly produced hormones which is secreted from the adrenal glands, and its physiological function is thought to be a precursor of sex steroids. DHEA-S has recently been shown to have physiological properties, such as neurosteroids, which are associated with such psychophysiological phenomena as memory, stress, anxiety, sleep and depression.

Therefore, the deficiency of DHEA-S might be related to the neuropsychiatric symptoms in patients with CFS.

 

Source: Kuratsune H, Yamaguti K, Sawada M, Kodate S, Machii T, Kanakura Y, Kitani T. Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome. Int J Mol Med. 1998 Jan;1(1):143-6. http://www.ncbi.nlm.nih.gov/pubmed/9852212

 

The relationship between temporomandibular disorders and stress-associated syndromes

Abstract:

OBJECTIVES: The purpose of this study was to determine the comorbidity of temporomandibular disorders and other stress-associated conditions in patients with chronic fatigue syndrome and fibromyalgia.

STUDY DESIGN: Of 92 patients who fulfilled the criteria for chronic fatigue syndrome or fibromyalgia (or both), 39 (42%) reported a prior diagnosis of temporomandibular disorder. Further questionnaires were sent to the members of this group, and 30 patients responded.

RESULTS: Of the original 92 patients, of whom 42% reported temporomandibular disorders, 46% had histories of irritable bowel syndrome, 42% of premenstrual syndrome, and 19% of interstitial cystitis. Of the patients with temporomandibular disorders, the great majority reported an onset of generalized symptoms before the onset of facial pain. Despite this, 75% had been treated exclusively for temporomandibular disorders, usually with bite splints.

CONCLUSIONS: Patients appearing for treatment with chronic facial pain show a high comorbidity with other stress-associated syndromes. The clinical overlap between these conditions may reflect a shared underlying pathophysiologic basis involving dysregulation of the hypothalamic-pituitary-adrenal stress hormone axis in predisposed individuals. A multidisciplinary clinical approach to temporomandibular disorders would improve diagnosis and treatment outcomes for this group of patients.

 

Source: Korszun A, Papadopoulos E, Demitrack M, Engleberg C, Crofford L. The relationship between temporomandibular disorders and stress-associated syndromes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Oct;86(4):416-20. http://www.ncbi.nlm.nih.gov/pubmed/9798224

 

Parallels between post-polio fatigue and chronic fatigue syndrome: a common pathophysiology?

Abstract:

Fatigue is the most commonly reported and most debilitating of post-polio sequelae affecting the >1.8 million North American polio survivors. Post-polio fatigue is characterized by subjective reports of difficulty with attention, cognition, and maintaining wakefulness. These symptoms resemble those reported in nearly 2 dozen outbreaks of post-viral fatigue syndromes (PVFS) that have recurred during this century and that are related clinically, historically, anatomically, or physiologically to poliovirus infections.

This article reviews recent studies that relate the symptoms of post-polio fatigue and chronic fatigue syndrome (CFS) to clinically significant deficits on neuropsychologic tests of attention, histopathologic and neuroradiologic evidence of brain lesions, impaired activation of the hypothalamic-pituitary-adrenal axis, increased prolactin secretion, and electroencephalogram (EEG) slow-wave activity.

A possible common pathophysiology for post-polio fatigue and CFS, based on the Brain Fatigue Generator Model of PVFS, and a possible pharmacotherapy for PVFS based on replacement of depleted brain dopamine, will be described.

 

Source: Bruno RL, Creange SJ, Frick NM. Parallels between post-polio fatigue and chronic fatigue syndrome: a common pathophysiology? Am J Med. 1998 Sep 28;105(3A):66S-73S. http://www.ncbi.nlm.nih.gov/pubmed/9790485

 

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

 

Blunted adrenocorticotropin and cortisol responses to corticotropin-releasing hormone stimulation in chronic fatigue syndrome

Abstract:

Hypofunctioning of the pituitary-adrenal axis has been suggested as the pathophysiological basis for chronic fatigue syndrome (CFS). Blunted adrenocorticotropin (ACTH) responses but normal cortisol responses to exogenous corticotropin-releasing hormone (CRH), the main regulator of this axis, have been previously demonstrated in CFS patients, some of whom had a comorbid psychiatric disorder. We wished to re-examine CRH activation of this axis in CFS patients free from concurrent psychiatric illness.

A sample of 14 patients with CDC-diagnosed CFS were compared with 14 healthy volunteers. ACTH and cortisol responses were measured following the administration of 100 microg ovine CRH. Basal ACTH and cortisol values did not differ between the two groups. The release of ACTH was significantly attenuated in the CFS group (P < 0.005), as was the release of cortisol (P < 0.05).

The blunted response of ACTH to exogenous CRH stimulation may be due to an abnormality in CRH levels with a resultant alteration in pituitary CRH receptor sensitivity, or it may reflect a dysregulation of vasopressin or other factors involved in HPA regulation. A diminished output of neurotrophic ACTH, causing a reduced adrenocortical secretory reserve, inadequately compensated for by adrenoceptor upregulation, may explain the reduced cortisol production demonstrated in this study.

 

Source: Scott LV, Medbak S, Dinan TG. Blunted adrenocorticotropin and cortisol responses to corticotropin-releasing hormone stimulation in chronic fatigue syndrome. Acta Psychiatr Scand. 1998 Jun;97(6):450-7. http://www.ncbi.nlm.nih.gov/pubmed/9669518

 

Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by profound fatigue and an array of diffuse somatic symptoms.

Our group has established that impaired activation of the hypothalamic-pituitary-adrenal (HPA) axis is an essential neuroendocrine feature of this condition. The relevance of this finding to the pathophysiology of CFS is supported by the observation that the onset and course of this illness is excerbated by physical and emotional stressors. It is also notable that this HPA dysregulation differs from that seen in melancholic depression, but shares features with other clinical syndromes (e.g., fibromyalgia).

How the HPA axis dysfunction develops is unclear, though recent work suggests disturbances in serotonergic neurotransmission and alterations in the activity of AVP, an important co-secretagogue that, along with CRH, influences HPA axis function.

In order to provide a more refined view of the nature of the HPA disturbance in patients with CFS, we have studied the detailed, pulsatile characteristics of the HPA axis in a group of patients meeting the 1994 CDC case criteria for CFS. Results of that work are consistent with the view that patients with CFS have a reduction of HPA axis activity due, in part, to impaired central nervous system drive. These observations provide an important clue to the development of more effective treatment to this disabling condition.

 

Source: Demitrack MA, Crofford LJ. Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann N Y Acad Sci. 1998 May 1;840:684-97. http://www.ncbi.nlm.nih.gov/pubmed/9629295