Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence is presented for an extra-adrenal effect of ACTH and ACTH analogs on muscle action potentials (APs), contractions and fatigue in in situ experiments. ACTH, alphaMSH, betaMSH and ACTH 4-10 increase the amplitude of APs and contractions and decrease fatigue in intact, hypophysectomized and in adrenalectomized rats, subjected to repetitive indirect stimulation (supermaximal strength, 5/sec or 10/sec for 30 min). Elevation of endogenous ACTH resulting from adrenalectomy or cold stress, or both, has the same effect as ACTH administration. ACTH peptides are most effective in depressed physiological conditions e.g. following hypophysectomy. As the effect of ACTH 4-10 is abolished after section of the motor nerve, it is inferred that this peptide may affect central motor neurons. Preliminary observations from clinical studies with ACTH 4-10 in patients with muscle disease, in whom a pathological decline in amplitude of a short series of evoked muscle APs was prevented by peptide administration, also indicate a possible action of this peptide on central nervous system neurons.
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PMID:Peptide enhancement of neuromuscular function: animal and clinical studies. 18 27

Systematical muscle exercises increased sensitivity of adrenals to ACTH in adult albino rats, while fatigue decreased it. The sensitivity of adenylatecyclase of fat cells to ACTH does not change during the adaptation of organism to increased muscular activity. Activation of adenylate cyclase of fat cells with epinephrine is abolished by sympatholytin which, however, has no effect on the ACTH activation. These findings confirm that the adenylate cyclase receptors for epinephrine and for ACTH are different.
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PMID:[Sensitivity to adrenocorticotropic hormone during adaptation to increased muscle activity]. 19 7

The ACTH was shown to increase whereas hydrocortisone entailed no changes of the muscle contraction amplitude, the duration of the muscle work to fatigue in the regimen of solitary rhythmic contractions being, however, shortened in both bases. The heat production for a unit of the muscle work remained the same after ACTH and decreased after hydrocortisone. The corticotropin increases whereas hydrocortisone decreases the efficiency of the energy substances usage by the working muscles.
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PMID:[Effect of corticotropin and hydrocortisone on the contractility and heat production of skeletal muscles]. 20 9

After discussion of the modern concepts of pathophysiology of ocular myasthenia the ocular symptoms such as ptosis and eye muscle palsies are discussed. As important diagnostic sign the Simpson lid fatigue test before and after application of Tensilon is described. For diagnosis of myasthenic eye muscle palsies electrooculography has a special significance especially in connection with the application of Edrophonium, which normalizes myasthenic hypometric saccades and transforms them even in hypermetric saccades. In doubtful cases of eye muscle palsies the electromyogram of the affected muscle in connection with the Edrophonium-test is extremely valuable. With regard to modern treatment apart from cholinesterase inhibitors (Pyridostigmine, Neostigmine) thymectomy, the application of corticosteroids, ACTH and especially also immune suppressive drugs (Imurel etc.) is discussed. Of great significance in ocular myasthenia is the local application of cholinesterase inhibitors like Eserine, Prostigmin or Phospholine Iodide.
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PMID:[Diagnosis and treatment of ocular myasthenia (author's transl)]. 20 42

After prolonged (8 hrs) swimming, the level of corticosteroids was reduced and the contents of aldosterone and DOC in the blood was increased in the rats. At incubation of these rats' adrenals in the L-thyrosine substratum the synthesis of adrenaline was reduced. Addition of hydrocortisone, prednisolone and corticosterone into the medium as well as in vivo administration of these increased the adrenaline synthesis in swimming rats and did not alter it in intact rats. Neither in vitro addition of aldosterone nor in vivo administration of ACTH activated the process. The activating effect of glucocorticoids was absent at incubation of the adrenals with L-DOPA and L-noradrenaline. Synthesis of cathecholamines in the heart of swimming rats in the presence of L-thyrosine and L-DOPA as precnrsors was suppressed; neither was it restored by administration of corticosteroids both in vitro and in vivo. This suggests that one of the reasons for suppression of the catecholamine synthesis in adrenals at obvious physical fatigue is the decrease of the glucocorticoid activity.
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PMID:[Interaction of catecholamines and corticosteroids during the process of muscle fatigue]. 20 48

A new method for the psychological and physical selection of aircrew is described. Data from the literature are cited in support of the proposition that, in muscular work tests, the response of the body to fatigue cannot only be measured by means of the usual spirometric and ECG methods, but also via the plasma cortisol, ACTH and STH response. It is shown that changes in the concentration of these hormones are mainly attributable to fatigue and its accompanying hypoglycaemia. Hitherto overlooked due to the lack of standardisation of its methods, endocrinological examination could, it is suggested, be of considerable assistance in the selection of aircrew, in the interests of greater safety in the air.
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PMID:[Behavior of plasma cortisol, ACTH and STH in subjects performing controlled work on the bicycle ergometer]. 21 42

A 74-year-old housewife was admitted to the hospital with complaints of high fever and general fatigue. The physical examinations on admission showed no particular findings except for mild hepatomegaly, but laboratory findings showed severe liver dysfunction, active inflammation and negative tuberculine test. On the 4th day, she suddenly complained of severe respiratory distress. A chest X-ray film demonstrated surprising changes in comparison with that taken on admission. On suspicion of adult respiratory distress syndrome (ARDS) associated with military tuberculosis (Miliary TB), administration of Methylpredonisolone (1000 mg a day for 3 days) in addition to antituberculous drugs was immediately started. With this therapy she was recovered from such ill condition, but the general exhaustion and slight fever continued. We suspected that her condition might be due to adrenocortical involvement of Miliary TB and hormonal examinations were performed. Unexpectedly, Cushing's syndrome was suspected on the basis of the following; high level of plasma cortisol without normal daily variation, normal ACTH level, an absent response to the Dexamethasone suppression test. Computed tomography revealed left side adrenal mass. During these examinations, renal dysfunction probably due to Miliary TB grew gradually worse and she died of renal failure on the 56th day. Necropsy revealed disseminated tuberculosis involving the lungs and the liver, but the adrenal glands were not examined.
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PMID:[A case of miliary tuberculosis (miliary TB) accompanied with adult respiratory distress syndrome (ARDS) in a patient with Cushing's syndrome]. 140 68

We describe a 55-year-old female who presented with a 1-year history of tiredness, depression and painful stiff joints. The most striking clinical abnormality was bilateral frozen shoulders, local corticosteroid treatment of which provided the first diagnostic clue. She was found to have profound diminution of plasma cortisol secondary to an isolated deficiency of ACTH. There was no obvious cause for this. Steroid replacement eradicated her lethargy within 3 months and evidence of frozen shoulders resolved completely.
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PMID:Isolated ACTH deficiency presenting with bilateral frozen shoulder. 164 65

Chronic fatigue syndrome is characterized by persistent or relapsing debilitating fatigue for at least 6 months in the absence of a medical diagnosis that would explain the clinical presentation. Because primary glucocorticoid deficiency states and affective disorders putatively associated with a deficiency of the arousal-producing neuropeptide CRH can be associated with similar symptoms, we report here a study of the functional integrity of the various components of the hypothalamic-pituitary-adrenal axis in patients meeting research case criteria for chronic fatigue syndrome. Thirty patients and 72 normal volunteers were studied. Basal activity of the hypothalamic-pituitary-adrenal axis was estimated by determinations of 24-h urinary free cortisol-excretion, evening basal plasma total and free cortisol concentrations, and the cortisol binding globulin-binding capacity. The adrenal cortex was evaluated indirectly by cortisol responses during ovine CRH (oCRH) stimulation testing and directly by cortisol responses to graded submaximal doses of ACTH. Plasma ACTH and cortisol responses to oCRH were employed as a direct measure of the functional integrity of the pituitary corticotroph cell. Central CRH secretion was assessed by measuring its level in cerebrospinal fluid. Compared to normal subjects, patients demonstrated significantly reduced basal evening glucocorticoid levels (89.0 +/- 8.7 vs. 148.4 +/- 20.3 nmol/L; P less than 0.01) and low 24-h urinary free cortisol excretion (122.7 +/- 8.9 vs. 203.1 +/- 10.7 nmol/24 h; P less than 0.0002), but elevated basal evening ACTH concentrations. There was increased adrenocortical sensitivity to ACTH, but a reduced maximal response [F(3.26, 65.16) = 5.50; P = 0.0015). Patients showed attenuated net integrated ACTH responses to oCRH (128.0 +/- 26.4 vs. 225.4 +/- 34.5 pmol/L.min, P less than 0.04). Cerebrospinal fluid CRH levels in patients were no different from control values (8.4 +/- 0.6 vs. 7.7 +/- 0.5 pmol/L; P = NS). Although we cannot definitively account for the etiology of the mild glucocorticoid deficiency seen in chronic fatigue syndrome patients, the enhanced adrenocortical sensitivity to exogenous ACTH and blunted ACTH responses to oCRH are incompatible with a primary adrenal insufficiency. A pituitary source is also unlikely, since basal evening plasma ACTH concentrations were elevated. Hence, the data are most compatible with a mild central adrenal insufficiency secondary to either a deficiency of CRH or some other central stimulus to the pituitary-adrenal axis. Whether a mild glucocorticoid deficiency or a putative deficiency of an arousal-producing neuropeptide such as CRH is related to the clinical symptomatology of the chronic fatigue syndrome remains to be determined.
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PMID:Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. 165 82

To explore whether possible differences in central nervous system neuromodulators contribute to the differential presentation of affective symptomatology in Cushing's disease and major depression, we examined the levels of immunoreactive CRH and ACTH in the cerebrospinal fluid (CSF) of 11 patients with Cushing's disease, a patient with ectopic ACTH secretion, 34 patients with major depression, and 60 healthy subjects. We elected to measure these peptides not only because both are classically involved in pituitary-adrenal regulation, but also because their primarily arousal-producing and anorexigenic behavioral effects in experimental animals suggest that they may play a role in the symptom complex of depressive syndromes. We also explored whether the CSF levels of these peptides were more helpful in determining the often difficult differential diagnosis between major depression and Cushing's disease than the plasma ACTH response to ovine CRH, a currently used but somewhat insensitive laboratory means of distinguishing these disorders. CSF levels of immunoreactive CRH and ACTH were significantly lower in Cushing's disease patients [21.9 +/- 2.7 and 15.4 +/- 1.8 pg/mL, (mean +/- SEM), respectively] compared to patients with major depression [38.4 +/- 2.3 pg/mL (P less than 0.01) and 24.5 +/- 1.6 pg/mL (P less than 0.01), respectively] and controls [38.4 +/- 1.6 pg/mL (P less than 0.001) and 26.3 +/- 1.1 pg/mL (P less than 0.001), respectively]. The coexistence of high plasma ACTH and low CSF ACTH in Cushing's disease yielded a CSF/plasma ACTH ratio consistently less than that in depressed patients, with only 2 of 31 subjects comprising both groups showing values that overlapped. In contrast, 9 of the combined patients showed ACTH responses to ovine CRH that overlapped. These data suggest that differences in centrally directed CRH secretion may account for the differential presentation of the dysphoric syndromes seen in major depression and Cushing's disease. Hence, the classic form of major depression (melancholia), is often associated with evidence of pathological hyperarousal, such as intense anxiety, sleeplessness, and anorexia, while that of Cushing's disease is associated with evidence of pathological hyperarousal, including hyperphagia, fatigue, and inertia. Moreover, measurement of the CSF/plasma ACTH ratio may serve as a clinically useful adjunct to the ovine CRH stimulation test and other laboratory measures in determining the differential diagnosis between major depression and Cushing's disease.
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PMID:Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing's disease and major depression: potential clinical implications. 199 96


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