Tag: hormones

Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a common and disabling disorder, and a major threat against adolescent health. The pathophysiology is unknown, but alteration of neuroendocrine control systems might be a central element, resulting in attenuation of the hypothalamus-pituitary-adrenalin (HPA) axis and enhancement of the sympathetic/adrenal medulla (SAM) system. This study explored differences in neuroendocrine control mechanisms between adolescent CFS patients and healthy controls, and whether characteristics of the control mechanisms are associated with important clinical variables within the CFS group.

METHODS: CFS patients 12-18 years of age were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied. A comparable group of healthy controls were recruited from local schools. A total of nine hormones were assayed and subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and daily physical activity was recorded by an accelerometer.

RESULTS: A total of 120 CFS patients and 68 healthy controls were included. CFS patients had significantly higher levels of plasma norepinephrine, plasma epinephrine and plasma FT4, and significantly lower levels of urine cortisol/creatinine ratio. Subgrouping according to other case definitions as well as adjusting for confounding factors did not alter the results. Multivariate linear regression models as well as network analyses revealed different interrelations between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls. Also, single hormone degree centrality was associated with clinical markers within the CFS group.

CONCLUSION: This study reveals different interrelation between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls, and an association between hormone control characteristics and important clinical variables in the CFS group. These results add to the growing insight of CFS disease mechanisms.

Trial registration Clinical Trials NCT010404

 

Source: Wyller VB, Vitelli V, Sulheim D, Fagermoen E, Winger A, Godang K, Bollerslev J. Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. J Transl Med. 2016 May 5;14(1):121. doi: 10.1186/s12967-016-0873-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858924/ (Full article)

 

Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators – relevance to chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a neuroimmunoendocrine disease affecting about 1% of the US population, mostly women. It is characterized by debilitating fatigue for six or more months in the absence of cancer or other systemic diseases. Many CFS patients also have fibromyalgia and skin hypersensitivity that worsen with stress. Corticotropin-releasing hormone (CRH) and neurotensin (NT), secreted under stress, activate mast cells (MC) necessary for allergic reactions to release inflammatory mediators that could contribute to CFS symptoms.

OBJECTIVE: To investigate the effect of isoflavones on the action of polyinosinic:polycytidylic acid (poly(I:C)), with or without swim stress, on mouse locomotor activity and inflammatory mediator expression, as well as on human MC activation.

METHODS: Female C57BL/6 mice were randomly divided into four groups: (a) control/no-swim, (b) control/swim, (c) polyinosinic:polycytidylic acid (poly(I:C))/no swim, and (d) polyinosinic:polycytidylic acid (poly(I:C))/swim. Mice were provided with chow low or high in isoflavones for 2 weeks prior to ip injection with 20 mg/kg poly(I:C) followed or not by swim stress for 15 minutes. Locomotor activity was monitored overnight and animals were sacrificed the following day. Brain and skin gene expression, as well as serum levels, of inflammatory mediators were measured. Data were analyzed using the non-parametric Mann-Whitney U-test.

RESULTS: Poly(I:C)-treated mice had decreased locomotor activity over 24 hours, and increased serum levels of TNF-α, IL-6, KC (IL-8/CXCL8 murine homolog), CCL2,3,4,5, CXCL10, as well as brain and skin gene expression of TNF, IL-6, KC (Cxcl1, IL8 murine homolog), CCL2, CCL4, CCL5 and CXCL10. Histidine decarboxylase (HDC) and NT expression were also increased, but only in the skin, over the same period. High isoflavone diet reversed these effects.

CONCLUSION: Poly(I:C) treatment decreased mouse locomotor activity and increased serum levels and brain and skin gene expression of inflammatory mediators. These effects were inhibited by isoflavones that may prove useful in CFS.

 

Source: Vasiadi M, Newman J, Theoharides TC. Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators – relevance to chronic fatigue syndrome. J Neuroinflammation. 2014 Oct 31;11:168. doi: 10.1186/s12974-014-0168-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236420/ (Full article)

 

Hormonal alterations in adolescent chronic fatigue syndrome

Abstract:

AIM: The chronic fatigue syndrome is associated with alterations in the hypothalamus-pituitary-adrenal axis and cardiovascular autonomic nervous activity, suggesting a central dysregulation. This study explored differences among adolescent chronic fatigue syndrome patients and healthy controls regarding antidiuretic hormone, the renin-angiotensin-aldosterone-system, sex hormones and cardiac peptides.

METHODS: We included a consecutive sample of 67 adolescents aged 12-18 years with chronic fatigue syndrome diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 55 healthy control subjects of equal gender and age distribution. Hormones were assayed with standard laboratory methods.

RESULTS: Among patients, plasma antidiuretic hormone was significantly decreased and serum osmolality and plasma renin activity were significantly increased (p < or = 0.001). Serum concentration of aldosterone, cortisol, NT-proBNP and sex hormones were not significantly different in the two groups.

CONCLUSION: Chronic fatigue syndrome in adolescents is associated with alterations in hormonal systems controlling osmolality and blood volume, possibly supporting a theory of central dysregulation.

 

Source: Wyller VB, Evang JA, Godang K, Solhjell KK, Bollerslev J. Hormonal alterations in adolescent chronic fatigue syndrome. Acta Paediatr. 2010 May;99(5):770-3. doi: 10.1111/j.1651-2227.2010.01701.x. Epub 2010 Mar 1. https://www.ncbi.nlm.nih.gov/pubmed/20199497

 

Reduced levels of oestrogen receptor beta mRNA in Swedish patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is an illness with unknown aetiology and pathophysiology. The difference in incidence by sex observed for CFS indicates a role for oestrogen and oestrogen receptors in disease development. Furthermore, an immunomediated pathogenesis has been suggested for CFS, providing an additional connection to oestrogen, which displays immunomodular functions.

AIMS: To investigate a possible association of oestrogen receptor (ER) mRNAs and two ERbeta single-nucleotide polymorphisms (SNPs) with CFS.

METHODS: Messenger RNA levels of ERalpha, ERbeta wt and ERbeta cx were investigated in peripheral blood mononuclear cells from 30 patients with CFS and 36 healthy controls by quantitative real-time polymerase chain reaction. Two ERbeta SNPs were scored in the same material.

RESULTS: The CFS group showed significantly lower mRNA expression levels of ERbeta wt compared with the healthy control group. No differences were observed for ERalpha or ERbeta cx between patients and controls. There were no significant differences in frequency for the investigated ERbeta SNPs between cases and controls.

CONCLUSIONS: The reduced ERbeta wt expression level observed in this study is consistent with an immune-mediated pathogenesis of CFS. Additionally, the observation that ERbeta wt expression is decreased in CFS could provide an entry point to identify interesting, potentially disease-causing, candidate molecules for further study. A possible connection between oestrogen, oestrogen receptors and CFS should be evaluated further.

 

Source: Gräns H, Nilsson M, Dahlman-Wright K, Evengård B. Reduced levels of oestrogen receptor beta mRNA in Swedish patients with chronic fatigue syndrome. J Clin Pathol. 2007 Feb;60(2):195-8. Epub 2006 May 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860629/

 

Chronic fatigue syndrome and high allostatic load

Abstract:

STUDY POPULATION: We examined the relationship between chronic fatigue syndrome (CFS) and allostatic load in a population-based, case-control study of 43 CFS patients and 60 nonfatigued, healthy controls from Wichita, KS, USA.

METHODS: An allostatic load index was computed for all study participants using available laboratory and clinical data, according to a standard algorithm for allostatic load. Logistic regression analysis was used to compute odds ratios (ORs) as estimates of relative risk in models that included adjustment for matching factors and education; 95% confidence intervals (CIs) were computed to estimate the precision of the ORs.

RESULTS: CFS patients were 1.9-times more likely to have a high allostatic load index than controls (95% CI = 0.75, 4.75) after adjusting for education level, in addition to matching factors. The strength of this association increased in a linear trend across categories of low, medium and high levels of allostatic load (p = 0.06).

CONCLUSION: CFS was associated with a high level of allostatic load. The three allostatic load components that best discriminated cases from controls were waist:hip ratio, aldosterone and urinary cortisol.

 

Source: Maloney EM, Gurbaxani BM, Jones JF, de Souza Coelho L, Pennachin C, Goertzel BN. Chronic fatigue syndrome and high allostatic load. Pharmacogenomics. 2006 Apr;7(3):467-73. https://www.ncbi.nlm.nih.gov/pubmed/16610956

 

Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS

Abstract:

There are a few reports that chronic fatigue syndrome (CFS) may be accompanied by changes in hormones, such as dehydroepiandrosterone (DHEA) and insulin-like growth factor (IGF1). This study examines the serum concentrations of DHEA-sulfate (DHEAS), IGF1 and IGF1 binding protein-3 (IGFBP3) in 20 patients with CFS and in 12 normal controls.

The IGFBP3/IGF1 ratio was computed as an index for IGF1 availability. We found significantly lower serum DHEAS concentrations in CFS, but no significant differences either in IGF1 or the IGFBP3/IGF1 ratio between CFS patients and normal controls. The decrease in serum DHEAS was highly sensitive and specific for CFS.

There were significant and positive correlations between serum DHEAS and serum zinc and the mitogen-induced expression of the CD69 molecule on CD3+CD8+ T cells (an indicator of early T cell activation). There was a significant and negative correlation between serum DHEAS and the increase in the serum alpha-2 protein fraction (an inflammatory marker). Serum IGF1, but not DHEAS, was significantly and inversely correlated to age.

The results show that CFS is accompanied by lowered levels of DHEAS and that the latter may play a role in the immune (defect in the early activation of T cells) and the inflammatory pathophysiology of CFS.

 

Source: Maes M, Mihaylova I, De Ruyter M. Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS. Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS. Neuro Endocrinol Lett. 2005 Oct;26(5):487-92. http://www.ncbi.nlm.nih.gov/pubmed/16264414

 

Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones

Abstract:

We investigated abnormalities of the hypothalamic-pituitary-gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones.

A total of 176 subjects participated – 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI).

Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05).

Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic-pituitary-gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations.

 

Source: Gur A, Cevik R, Nas K, Colpan L, Sarac S. Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones.  Arthritis Res Ther. 2004;6(3):R232-8. Epub 2004 Mar 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC416440/ (Full article)

 

Hormonal responses to exercise in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating disease characterized by severe, unexplained fatigue and postexertional exacerbation of symptoms. We examined basal endocrine function in a group of CFS patients and a carefully matched group of sedentary controls. The subjects then completed a graded, maximal exercise test on a treadmill, and additional blood samples were drawn 4 min and a day after the end of exercise.

There were no differences in basal hormone levels before exercise. Plasma adrenocorticotropin, epinephrine, prolactin and thyrotropin responses 4 min after exercise were lower in the CFS group, but the growth hormone response may have been exaggerated, and the plasma norepinephrine response was similar to that in controls.

The next day, there were no differences in hormone levels between the groups, which suggests that long-term changes in endocrine function are unlikely to be a cause of the prolonged fatigue that occurs in CFS patients after a bout of exertion.

 

Source: Ottenweller JE, Sisto SA, McCarty RC, Natelson BH. Hormonal responses to exercise in chronic fatigue syndrome. Neuropsychobiology. 2001 Jan;43(1):34-41. http://www.ncbi.nlm.nih.gov/pubmed/11150897

 

The psychotherapeutic effects of estrogens

Abstract:

The effect of estrogens on the central nervous system, particularly mood and behavior, remains a controversial area which needs clarification, not just for understanding of depression in women but to ensure that such commonplace problems in women have efficient and appropriate therapy.

There is now good evidence that estrogens are rapidly effective in the treatment of depression in many women but this information has not found its way through to those health care personnel, psychiatrists and psychologists who are principally involved in the treatment of depression. There is also strong evidence for the benefits of estrogens on cognitive functioning, not only in preventing the onset of dementia but also in improving the symptoms in the established condition.

Recent work has also suggested a benefit for estrogens on mood in women diagnosed as suffering from chronic fatigue syndrome. This article reviews the effect of endogenous estrogen on the female central nervous system and the ever increasing evidence for the diverse psychotherapeutic effects of exogenous estrogens.

 

Source: Panay N, Studd JW. The psychotherapeutic effects of estrogens. Gynecol Endocrinol. 1998 Oct;12(5):353-65. http://www.ncbi.nlm.nih.gov/pubmed/9859029

 

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