Chronic fatigue syndrome: an endocrine disease off limits for endocrinologists?

Abstract:

Endocrinologists were not included in the multidisciplinary working groups that prepared two recent reports on chronic fatigue syndrome, despite its unequalled clinical overlap with Addison’s disease, which is a classic endocrine disorder. The failure to include at least one endocrinologist in those panels may explain why in their extensive reports there is not a single word about the 42 clinical features that chronic fatigue syndrome shares with Addison’s disease, including all the signs and symptoms listed in the case definition of this syndrome.

Comment in: Dr Baschetti rides/writes again. [Eur J Clin Invest. 2004]

 

Source: Baschetti R. Chronic fatigue syndrome: an endocrine disease off limits for endocrinologists? Eur J Clin Invest. 2003 Dec;33(12):1029-31. http://www.ncbi.nlm.nih.gov/pubmed/14636284

 

The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures

Abstract:

Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity.

This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary.

The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity.

In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range of neurological consequences, some of which were headache, general debilitating pains, fever, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, and seizures.

 

Source: Anyanwu E, Campbell AW, Jones J, Ehiri JE, Akpan AI. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures. ScientificWorldJournal. 2003 Nov 13;3:1128-37. http://www.hindawi.com/journals/tswj/2003/307098/abs/

 

Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness

Abstract:

Abnormal cardiovascular stress responses have been reported in Gulf War veterans with chronic fatigue. However, many of these veterans also suffer from posttraumatic stress disorder (PTSD), which could potentially explain the reported abnormalities. To test this hypothesis, 55 Gulf veterans (GVs) with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) were stratified into groups with (N=16) and without (N=39) comorbid PTSD, and were compared to healthy Gulf veterans (N=47) on cardiovascular responses to a series of stressors.

The CFS/ICF with PTSD group had lower blood pressure responses to speech and arithmetic tasks, and more precipitous declines and slower recoveries in blood pressure after standing up than the controls. Similar trends in the CF/ICF group without PTSD were not significant, however. Both CFS/ICF groups had blunted increases in peripheral vascular resistance during mental tasks. However, only the veterans with comorbid PTSD had diminished cardiac output responses to the mental stressors and excessive vasodilatory responses to standing. Symptoms of posttraumatic stress were significant predictors of hypotensive postural responses, but only in veterans reporting a significant exposure to wartime stress.

We conclude that comorbid PTSD contributes to dysregulation of cardiovascular responses to mental and postural stressors in Gulf veterans with medically unexplained fatiguing illness, and may provide a physiological basis for increased somatic complaints in Gulf veterans with symptoms of posttraumatic stress.

 

Source: Peckerman A, Dahl K, Chemitiganti R, LaManca JJ, Ottenweller JE, Natelson BH. Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness. Auton Neurosci. 2003 Oct 31;108(1-2):63-72. http://www.ncbi.nlm.nih.gov/pubmed/14614966

 

A population-based study of the clinical course of chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) presents a challenge for patients, health care providers, and health insurance groups because of its incapacitating nature, unknown cause, and poorly understood prognosis. We conducted a longitudinal population-based study to characterize the clinical course of CFS.

METHODS: Sixty-five CFS subjects were identified from a random-digit-dialing survey of Wichita, Kansas residents and followed for up to 3 years. We evaluated changes in CFS classification (partial or total remission, alternative medical or psychiatric diagnoses), CFS case-defining criteria, wellness scores, hours of activities and sleep, and treatments used to reduce fatigue. Associations between risk factors and outcomes were determined by use of logistic regression and generalized estimating equations models.

RESULTS: Only 20%-33% of the subjects were classified as having CFS at follow-up, 56.9% ever experienced partial or total remission, 10% sustained total remission, and 23.1% received alternative diagnoses, of which 20% were sleep disorders. Higher fatigue severity scores and total number of symptoms were negatively associated with ever remitting. Duration of illness < or = 2 years was positively associated with sustained remission. Unrefreshing sleep persisted in at least 79% of the subjects across all periods but, as with most of the CFS symptoms, tended to be less frequent over time. The number of activities affected by fatigue decreased over time, while wellness scores increased. At any follow-up, more than 35% of subjects reporting reduced fatigue used complementary and alternative medicine therapies, and of those subjects, at least 50% thought these therapies were responsible for reducing their fatigue.

CONCLUSIONS: The clinical course of CFS was characterized by an intermittent pattern of relapse and remission. Remission rates documented by our population-based study were similar to those reported in clinical studies. Shorter illness duration was a significant predictor of sustained remission, and thus early detection of CFS is of utmost importance. The persistence of sleep complaints and identification of sleep disorders suggest that CFS subjects be evaluated for sleep disturbances, which could be treated.

Comment in: Chronic fatigue and chronic fatigue syndrome in the general population. [Health Qual Life Outcomes. 2003]

 

Source: Nisenbaum R, Jones JF, Unger ER, Reyes M, Reeves WC. A population-based study of the clinical course of chronic fatigue syndrome. Health Qual Life Outcomes. 2003 Oct 3;1:49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC269990/ (Full article)

 

Chronic fatigue and chronic fatigue syndrome in the general population

Both chronic fatigue (CF) connected to a chronic or serious disease, and Chronic Fatigue Syndrome (CFS) form a serious problem in our Western society. It causes a lot of suffering for patients and may lead to disability to work. Doctors are frequently confronted with these patients, but it is unknown how many of these patients are suffering without help-seeking.

Most research has been done in CFS, and in specialised CFS clinics. Much less is known about other types of chronic fatigue, connected with a serious disabling disease, or with a psychiatric condition. There is hardly any knowledge about the prevalence and characteristics of these types of chronic fatigue and especially CFS, and the course of CFS in the general population. If we would know more about fatigue and chronic fatigue in the general population then, for example, the development of prevention programs would become nearer.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC269992/

 

Comment on:

Functional status of persons with chronic fatigue syndrome in the Wichita, Kansas, population. [Health Qual Life Outcomes. 2003]

A population-based study of the clinical course of chronic fatigue syndrome. [Health Qual Life Outcomes. 2003]

 

Source: Bleijenberg G. Chronic fatigue and chronic fatigue syndrome in the general population. Health Qual Life Outcomes. 2003 Oct 6;1:52. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC269992/ (Full article)

 

Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome

 Abstract:

Chronic fatigue syndrome (CFS) is a controversial entity whose cause is unknown. In this study we have explored the possibility that progesterone metabolites may be involved. Plasma levels of the progesterone precursor pregnenolone, progesterone itself, and five ring A-reduced metabolites of progesterone were measured in 20 women with CFS and in 13 age-matched controls.

To minimize the contribution of the ovary, women were either post-menopausal or in the follicular phase of the menstrual cycle (day 4-8), and progesterone levels were all well within the expected range (< or = 3.5 nmol/l). Mean values for progesterone and all of its metabolites were higher in CFS patients, the most marked being a 2.3-fold elevation in isopregnanolone (3beta,5alpha-tetrahydroprogesterone; p < or = 0.001). Progesterone levels were correlated with those of its metabolites, but even after controlling for progesterone by ANCOVA, isopregnanolone levels were still elevated (p < or = 0.001). These elevated levels of isopregnanolone could not be attributed to medications (antidepressants and anxiolytics).

When the CFS patients were divided into two groups according to their Hamilton depression scale ratings, mean (+/-SD) isopregnanolone levels were higher (274+/-160 vs 197+/-119 pmol/l) in the less depressed group (ratings 2-14) than in the more depressed group (ratings 17-28), although this difference did not reach significance. Progesterone levels were negatively correlated with Hamilton depression rating scores (r=-0.56; p<0.01). These results suggest that increases in ring A-reduced progesterone metabolites, particularly isopregnanolone, are associated with CFS, and that the pathophysiology of CFS is unlikely to be due to depression.

 

Source: Murphy BE, Abbott FV, Allison CM, Watts C, Ghadirian AM. Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome. Psychoneuroendocrinology. 2004 Feb;29(2):245-68. http://www.ncbi.nlm.nih.gov/pubmed/14604604

 

Association between serotonin transporter gene polymorphism and chronic fatigue syndrome

Abstract:

Interaction between the hypothalamo-pituitary-adrenal axis and the serotonergic system is thought to be disrupted in chronic fatigue syndrome(CFS) patients. We examined a serotonin transporter (5-HTT) gene promoter polymorphism, which affects the transcriptional efficiency of 5-HTT, in 78 CFS patients using PCR amplification of the blood genomic DNA.

A significant increase of longer (L and XL) alleic variants was found in the CFS patients compared to the controls both by the genotype-wise and the allele-wise analyses (both p<0.05, by chi(2) test and Fisher’s exact test). Attenuated concentration of extracellular serotonin due to longer variants may cause higher susceptibility to CFS.

 

Source: Narita M, Nishigami N, Narita N, Yamaguti K, Okado N, Watanabe Y, Kuratsune H. Association between serotonin transporter gene polymorphism and chronic fatigue syndrome. Biochekm Biophys Res Commun. 2003 Nov 14;311(2):264-6. http://www.ncbi.nlm.nih.gov/pubmed/14592408

 

An investigation into the psychometric properties of the Hospital Anxiety and Depression Scale in individuals with chronic fatigue syndrome

Abstract:

The study sought to determine the psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in individuals with chronic fatigue syndrome (CFS) assessed using a web-based data collection tool. Exploratory and confirmatory factor analyses were conducted on the HADS to determine its psychometric properties in 117 individuals with CFS. Seven models were tested to determine model fit to the data.

Internal reliability estimations of the anxiety and depression sub-scales were found to be acceptable, however, a three-factor model was found to provide a significantly better fit to the data when compared to the bi-dimensional two-factor structure previously assumed to underpin the HADS’ construct validity.

The clinical utility of the HADS in the assessment of anxiety and depression in CFS appears to be fundamentally compromised by the presence of a three-dimensional underlying factor structure. Future revision of the HADS is recommended if the instrument is to be used reliably to screen CFS patients.

 

Source: McCue P, Martin C, Buchanan T, Rodgers J, Scholey A. An investigation into the psychometric properties of the Hospital Anxiety and Depression Scale in individuals with chronic fatigue syndrome. Psychol Health Med. 2003 Nov;8(4):425-39. doi: 10.1080/1354850310001604568. http://www.ncbi.nlm.nih.gov/pubmed/21974733

 

Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study

Abstract:

BACKGROUND: The role of stress in the onset of chronic fatigue syndrome is unclear. Our objectives in this study were first, to determine the relation between the onset of chronic fatigue syndrome and stressful life events and difficulties. Secondly, we examined the role of a particular type of problem, dilemmas, in the onset of chronic fatigue syndrome.

METHOD: We used a case-control design with 64 consecutive referrals from an Infectious Diseases/ Liaison Psychiatry Fatigue clinic and 64 age- and sex-matched controls from a general practice population control group in Leeds. We had two main outcome measures; the odds ratios of the risk of developing chronic fatigue syndrome after experiencing a severe life event, severe difficulties or both in the year and 3 months preceding onset; and the proportion of subjects in each group who experienced a dilemma prior to onset.

RESULTS: Patients with chronic fatigue syndrome were more likely to experience severe events and difficulties in the 3 months (OR = 9, 95% CI 3.2 to 25.1) and year (OR = 4.3, 95% CI 1.8 to 10.2) prior to onset of their illness than population controls. In the 3 months prior to onset 19 of the 64 patients (30%) experienced a dilemma compared to none of the controls.

CONCLUSIONS: Chronic fatigue syndrome is associated with stressful events and difficulties prior to onset. Those events and difficulties characterized as being dilemmas seem to be particularly important.

 

Source: Hatcher S, House A. Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study. Psychol Med. 2003 Oct;33(7):1185-92. http://www.ncbi.nlm.nih.gov/pubmed/14580073

 

Muscle metabolism with blood flow restriction in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether chronic fatigue syndrome (CFS) is associated with reduced blood flow and muscle oxidative metabolism. Patients with CFS according to Centers for Disease Control criteria (n = 19) were compared with normal sedentary subjects (n = 11).

Muscle blood flow was measured in the femoral artery with Doppler ultrasound after exercise. Muscle metabolism was measured in the medial gastrocnemius muscle with (31)P-magnetic resonance spectroscopy. Muscle oxygen saturation and blood volume were measured using near-infrared spectroscopy. CFS and controls were not different in hyperemic blood flow or phosphocreatine recovery rate. Cuff pressures of 50, 60, 70, 80, and 90 mmHg were used to partially restrict blood flow during recovery. All pressures reduced blood flow and oxidative metabolism, with 90 mmHg reducing blood flow by 46% and oxidative metabolism by 30.7% in CFS patients.

Hyperemic blood flow during partial cuff occlusion was significantly reduced in CFS patients (P < 0.01), and recovery of oxygen saturation was slower (P < 0.05). No differences were seen in the amount of reduction in metabolism with partially reduced blood flow.

In conclusion, CFS patients showed evidence of reduced hyperemic flow and reduced oxygen delivery but no evidence that this impaired muscle metabolism. Thus CFS patients might have altered control of blood flow, but this is unlikely to influence muscle metabolism. Furthermore, abnormalities in muscle metabolism do not appear to be responsible for the CFS symptoms.

 

Source: McCully KK, Smith S, Rajaei S, Leigh JS Jr, Natelson BH. Muscle metabolism with blood flow restriction in chronic fatigue syndrome. J Appl Physiol (1985). 2004 Mar;96(3):871-8. Epub 2003 Oct 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680353/ (Full article)