Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Generalized tendomyopathy (GTM), or fibromyalgia (FM), is a disease characterized by wide-spread pain in the musculoskeletal system which usually begins at a single site, e.g., as low-back pain or cervical syndrome, and develops into generalized pain over months or years. The disorder affects primarily women, beginning around the age of 35 and reaching its peak during or after the menopause. Its etiology is still unknown. Secondary forms are observed particularly in rheumatoid arthritis. In order to get more information on FM we determined the local metabolic rate of glucose in vivo in the skeletal muscle (lumbar region) with dynamic 18F-FDG positron emission tomography (PET). 2 healthy volunteers and 6 female patients with FM reaching in age from 31 to 53 years were scanned. As 18F-FDG PET scanning is a metabolic tool, it is crucial to observe standardized conditions of metabolic steady-state. We used, therefore, the hyperinsulinemic euglycemic insulin clamp technique to stimulate the myogenic glucose uptake under stable plasma-glucose levels. The local metabolic rates of glucose utilization were estimated with a non-linear least squares fit on the 3 compartment 18F-FDG-model. A lumped constant of 0.67 was assumed. Under glucose clamp conditions patients with FM showed a significantly (p < 0.001) lower metabolic rate of glucose (4.3 +/- 1.1) mumol/100 g tissue/min compared with normal volunteers (8.5 +/- 2.3 mumol/100 g/min). Due to a significantly (p < 0.005) increased glucose backflow from tissue into the vascular space (k2 in the kinetic model) the rate of phosphorylation was markedly reduced in patients with FM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Determination of regional rate of glucose metabolism in lumbar muscles in patients with generalized tendomyopathy using dynamic 18F-FDG PET]. 147 8

The reactivity of the hypothalamic-pituitary-adrenal (HPA) axis was investigated in 10 female patients fulfilling the Yunus criteria for the primary fibromyalgia syndrome (PFS) and in 10 matched, healthy and sedentary controls. The 2 groups were subjected to a dexamethasone suppression (DXM) test, a corticotropin-releasing hormone (CRH) test and an insulin induced hypoglycemia (IH) test. In the DXM test there was no escape from suppression in patients or controls. The CRH and the IH tests showed a markedly enhanced, and statistically significant, adrenocorticotropic hormone (ACTH) release in patients with PFS versus controls, while the cortisol response in both groups was not different. Our data suggest that fibromyalgia is related to a neuroendocrine disorder characterized by hyperreactive pituitary ACTH release and a relative adrenal hyporesponsiveness. This HPA response pattern is unique and contrasts to the hypercortisolemic responses observed in affective disorders, e.g., depression, which like PFS, are often thought to be precipitated by chronic stress. Our findings seem to indicate a relative adrenal insufficiency in PFS, which might serve clinically as an explanation for the reduced aerobic capacity and impaired muscle performance these patients display.
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PMID:Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. 847 45

Fibromyalgia (FM) falls into the spectrum of what might be termed 'stress-associated syndromes' by virtue of frequent onset after acute or chronic stressors and apparent exacerbation of symptoms during periods of physical or emotional stress. Patients with FM exhibit disturbances of the major stress-response systems, the HPA axis and the sympathetic nervous system. Integrated basal cortisol levels measured by 24-hour urine-free cortisol are low. FM patients display a unique pattern of HPA axis perturbation characterized by exaggerated ACTH response to exogenous CRH or to endogenous activators of CRH such as insulin-induced hypoglycaemia. The cortisol response to increased ACTH in these stress paradigms is blunted, as is the the cortisol response to exercise. Functional analysis suggests that FM patients may also exhibit disturbed autonomic system activity. For example, plasma NPY, a peptide co-localized with norepinephrine in the sympathetic nervous system, is low in patients with FM. Abnormalities of related neuronal systems, particularly decreased serotonergic activity, may contribute to the observed neuroendocrine perturbations in FM. Finally, other neuroendocrine systems, including the growth hormone axis, are also abnormal in FM patients. Many clinical features of FM and related disorders, such as widespread pain and fatigue, could be related to the observed neuroendocrine perturbations. This hypothesis is supported by the observation that many useful treatments for FM affect the function of these central nervous system centres. Further clarification of the role of neuroendocrine abnormalities in patients with FM, and the relationship of these disturbances with particular symptoms, may lead to improved therapeutic strategies.
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PMID:Neurohormonal perturbations in fibromyalgia. 891 54

Recently, fibromyalgia (FMS) was shown to be a disorder associated with an altered functioning of the stress response system. FMS patients display a hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin-induced hypoglycemia. We suggested that negative feedback of cortisol could be deranged. Therefore we investigated the properties and function of the glucocorticoid receptors (GR) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition). Forty primary FMS patients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sedentary control persons were recruited for the study. Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls. Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls. However, plasma free cortisol concentrations were similar in the three groups. There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation constant (Kd) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/l) subjects was significantly higher than that of the controls (10.9 +/- 0.8 nmol/l) (p < .05). The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05) than in the control or LBP group. The ED50 (the cortisol concentration giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups. We conclude that FMS patients have a mild hypocortisolemia, increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus. The role of the GR and mineralocorticoid receptor (MR) in the CRH regulation in the FMS patients remains to be solved.
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PMID:Glucocorticoid receptors, fibromyalgia and low back pain. 948 5

Decreased serum levels of insulin-like growth factor I (IGF-I) are common in patients with fibromyalgia, which is frequently associated with chronic fatigue syndrome (CFS). Twenty patients with CFS (7 men, 13 women; age range, 30-60 years) and age- and sex-matched controls were tested for peak GH responses to insulin-induced hypoglycaemia and arginine administration. Nocturnal secretion of GH and serum levels of IGF-I were also measured. Serum IGF-I SDS (+/- SD) was significantly lower in patients with CFS than in controls (SDS, -0.39 +/- 1.07 vs 0.33 +/- 0.84; P = 0.02). Patients with CFS also tended to have reduced nocturnal secretion of GH (area under the curve, 32.4 +/- 18.3 vs 62.7 +/- 43.7 microg/l/15 minutes; P= 0.06), but peak GH responses to insulin-induced hypoglycaemia and arginine administration did not differ significantly between the two groups. It is not clear whether the tendency for impaired spontaneous nocturnal GH secretion in patients with CFS is a cause or an effect of the condition.
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PMID:Secretion of growth hormone in patients with chronic fatigue syndrome. 1099 Jan 47

The pineal hormone melatonin is the mediator of external light to physiologic adaptation to day and night rhythms, it regulates reproduction in animals but attempts to utilize melatonin in women for contraception have failed. Melatonin seems to be the natural hormone to facilitate sleep in insomniac patients and causes no hang over. When applied together with benzodiazepine it allows reduction of benzodiazepine without withdrawal effects. It should be applied 2 h before sleeping time in doses between 3 and 5 mg. Melatonin acts via the gamma-aminobutyric acid- and benzodiazepine receptor explaining its success in treatment of seizures in children and in adults. Constant application of benzodiazepine reduced the production of natural melatonin in rats, supporting the evidence that long-term application of benzodiazepine in humans does not restore sleeping habits but reduces natural sleeping habits even more. Low melatonin levels were seen in bulimia or neuralgia and in women with fibromyalgia; replacement reduced pain, sleeping disorders, and depression in fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish between several forms of depression, like major depression, winter depression (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with a major depression success with antidepressants correlated with an increase in their melatonin profiles but only patients suffering from DSPS can be successfully treated with melatonin. In perimenopausal women melatonin administration did produce a change in LH, FSH and thyroid hormones. Some oncostatic properties are supported by cell culture work and studies in animals. In Nordic countries indigenous people suffer less from breast and prostate cancer, winter darkness seems to protect. The supposedly increased melatonin levels created the 'melatonin hypothesis'. Epidemiological studies did show that blind people indeed have half the rate of breast cancers, supporting the hypothesis. Controversial results concerning melatonin and insulin resistance and glucose tolerance have been published. In postmenopausal women application of melatonin reduced glucose tolerance and insulin sensitivity. Pregnant women should avoid melatonin, since its teratogenic effect is not known. Patients suffering from non-hormone dependent tumors, like leukemia, should avoid melanin, since tumor growth was promoted in animal experiments. It can be expected that melatonin will receive wide consideration for treatment of sleeping disturbances, jet lag, and fibromyalgia once an oral formulation becomes available in Europe.
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PMID:Melatonin deficiencies in women. 1195 97

The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.
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PMID:Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. 1237 95

It has long been recognized that the symptom complex of fibromyalgia can be seen with hypothyroidism. Hypothyroidism may been categorized, like diabetes, into type I (hormone deficient) and type II (hormone resistant). Most cases of fibromyalgia fall into the latter category. The syndrome is reversible with treatment, and is usually of late onset. It is likely more often acquired than due to mutated receptors. Now that there is evidence to support the hypothesis that fibromyalgia may be due to thyroid hormone resistance, four major questions appear addressable. First, can a simple biomarker be found to help diagnose it? Second, what other syndromes similar to Fibromyalgia may share a thyroid-resistant nature? Third, in non-genetic cases, how is resistance acquired? Fourth, what other methods of treatment become available through this new understanding? Preliminary evidence suggests that serum hyaluronic acid is a simple, inexpensive, sensitive, and specific test that identifies fibromyalgia. Overlapping symptom complexes suggest that chronic fatigue syndrome, Gulf war syndrome, premenstrual syndrome, post traumatic stress disorder, breast implant silicone sensitivity syndrome, bipolar affective disorder, systemic candidiasis, myofascial pain syndrome, and idiopathic environmental intolerance are similar enough to fibromyalgia to merit investigation for possible thyroid resistance. Acquired resistance may be due most often to a recently recognized chronic consumptive coagulopathy, which itself may be most often associated with chronic infections with mycoplasmids and related microbes or parasites. Other precipitants of thyroid resistance may use this or other paths as well. In addition to experimentally proven treatment with supraphysiologic doses of thyroid hormone, the thyroid-resistant disorders might be treatable with anti-hypercoagulant, anti-infective, insulin-sensitizing, and hyaluronolytic strategies.
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PMID:A metabolic basis for fibromyalgia and its related disorders: the possible role of resistance to thyroid hormone. 1288

Research indicates that exposure to traumatic stressors and psychological trauma is widespread. The association of such exposures with posttraumatic stress disorder (PTSD) and other mental health conditions is well known. However, epidemiologic research increasingly suggests that exposure to these events is related to increased health care utilization, adverse health outcomes, the onset of specific diseases, and premature death. To date, studies have linked traumatic stress exposures and PTSD to such conditions as cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, chronic fatigue syndrome, musculoskeletal disorders, and other diseases. Evidence linking cardiovascular disease and exposure to psychological trauma is particularly strong and has been found consistently across different populations and stressor events. In addition, clinical studies have suggested the biological pathways through which stressor-induced diseases may be pathologically expressed. In particular, recent studies have implicated the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) stress axes as key in this pathogenic process, although genetic and behavioral/psychological risk factors cannot be ruled out. Recent findings, indicating that victims of PTSD have higher circulating T-cell lymphocytes and lower cortisol levels, are intriguing and suggest that chronic sufferers of PTSD may be at risk for autoimmune diseases. To test this hypothesis, we assessed the association between chronic PTSD in a national sample of 2,490 Vietnam veterans and the prevalence of common autoimmune diseases, including rheumatoid arthritis, psoriasis, insulin-dependent diabetes, and thyroid disease. Our analyses suggest that chronic PTSD, particularly comorbid PTSD or complex PTSD, is associated with all of these conditions. In addition, veterans with comorbid PTSD were more likely to have clinically higher T-cell counts, hyperreactive immune responses on standardized delayed cutaneous hypersensitivity tests, clinically higher immunoglobulin-M levels, and clinically lower dehydroepiandrosterone levels. The latter clinical evidence confirms the presence of biological markers consistent with a broad range of inflammatory disorders, including both cardiovascular and autoimmune diseases.
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PMID:Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. 1567 1

Standard radioimmunoassay (RIA) was employed to quantify basal serum growth hormone (GH), insulin-like growth factor-I (IGF-1), and insulin levels in 32 normoglycemic patients with clinically active fibromyalgia and in 29 normoglycemic control subjects. The GH concentration was significantly higher (P < 0.001) in female fibromyalgia patients than age-matched, normal female subjects. In contrast, basal serum IGF-1 concentrations did not differ between these groups. A scatter plot generated from two-stage, least-squares analysis showed that serum GH lacked correlation with the serum IGF-1 concentrations of normal female subjects (P = 0.73) and female fibromyalgia patients (P = 0.19). In addition to the results from serum GH and IGF-1 RIA, we also found significantly higher fasting serum insulin levels (P = 0.03) in male fibromyalgia patients and a trend toward elevated fasting serum insulin levels in the female fibromyalgia population ( P = 0.07), with the mean fasting level in the male fibromyalgia group (35.7 microU/ml(-1)) exceeding the upper limit of normal serum insulin levels (i.e., 27 microU/ml(-1)). Based on these results, basal serum GH and fasting serum insulin levels appear to be valuable surrogate markers in clinically active, normoglycemic fibromyalgia patients.
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PMID:Serum growth hormone and insulin but not insulin-like growth factor-1 levels are elevated in patients with fibromyalgia syndrome. 1575 59


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