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)

Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are adrenal precursors of steroid biosynthesis and centrally acting neurosteroids. Glucocorticoid and mineralocorticoid deficiencies in Addison's disease require life-long hormone replacement, but the associated failure of DHEA synthesis is not corrected. We conducted a randomized, double blind study in which 39 patients with Addison's disease received either 50 mg oral DHEA daily for 12 weeks, followed by a 4-week washout period, then 12 weeks of placebo, or vice versa. After DHEA treatment, levels of DHEAS and Delta(4)-androstenedione rose from subnormal to within the adult physiological range. Total testosterone increased from subnormal to low normal with a fall in serum sex hormone-binding globulin in females, but with no change in either parameter in males. In both sexes, psychological assessment showed significant enhancement of self-esteem with a tendency for improved overall well-being. Mood and fatigue also improved significantly, with benefit being evident in the evenings. No effects on cognitive or sexual function, body composition, lipids, or bone mineral density were observed. Our results indicate that DHEA replacement corrects this steroid deficiency effectively and improves some aspects of psychological function. Beneficial effects in males, independent of circulating testosterone levels, suggest that it may act directly on the central nervous system rather than by augmenting peripheral androgen biosynthesis. These positive effects, in the absence of significant adverse events, suggest a role for DHEA replacement therapy in the treatment of Addison's disease.
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PMID:Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. 1113 23

A 32-year-old student reported fatigue and malaise since two months in the absence of specific symptoms. Clinical examination and extensive laboratory testing revealed no abnormalities at his first presentation. Some weeks thereafter, on re-admission, hyperpigmentation suggestive of Addison's disease was observed and pathognomonic autoantibodies directed against the thyroid gland and the adrenal cortex were detected. Further evaluation led to the diagnosis autoimmune polyglandular deficiency syndrome, also named "Schmidt syndrome", comprising adrenocortical insufficiency (Addison's disease) and lymphocytic thyroiditis (Hashimoto thyroiditis). The diagnosis of polyglandular insufficiency is often delayed due to non-specific symptoms at early disease stages and progression may be rapid, culminating in Addisonian crisis under physical stress or infection, requiring immediate high-dose hormone replacement therapy. Hence, careful re-examination is mandatory to ensure adequate treatment before life-threatening complications occur. Nowadays this type of disease is classified as autoimmune polyglandular syndrome type II (APS type II) with an increased risk of developing insulin-dependent diabetes mellitus (IDDM), vitiligo, alopecia, pernicious anaemia, coeliac disease, myasthenia gravis and primary hypogonadism. The cause of the disease remains obscure but in addition to an autosomal dominant trait with variable penetrance some hints at viral infection triggering the disease process exist.
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PMID:32-year old patient presenting with autoimmune polyglandular syndrome. 1131 87

In nine patients with Addison's disease (mean +/- SE: 51 +/- 2 years) receiving conventional steroid treatment, and nine age-matched healthy controls (56 +/- 2 years), we investigated maximum voluntary quadriceps force (MVC) and contractile properties evoked with stimulation and central activation both at rest and during a submaximal intermittent fatigue task. The MVC was similar (-3%), but twitch tension (-27%) and central activation were significantly less (-7%), and tetanic half-relaxation time was approximately 40% slower in the patients. Twitch amplitudes were potentiated by 6% in the patients, but unchanged in the control group. The patients self-terminated a submaximal intermittent fatigue protocol (0.6 duty cycle) at approximately 5 +/- 1 min, whereas the controls stopped when they lost 50% of MVC force ( approximately 10 +/- 1 min). Force loss was similar between groups over the first 5 min of the fatigue task. In the patient group, maximal and submaximal relative integrated electromyogram (IEMG) increased significantly in the first minute of fatigue and remained elevated, whereas the controls exhibited a gradual increase in submaximal IEMG with little change in maximal IEMG. These results indicate that conventionally treated Addison's patients have similar MVC strength, but altered contractile properties and decreased endurance compared with controls.
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PMID:Quadriceps muscle function and fatigue in women with Addison's disease. 1143 79

We report here a patient with myelodysplastic syndromes (MDS), which was complicated with several autoimmune disorders and asymptomatic immunologic abnormalities. An 82-year-old woman with refractory anemia (RA) rapidly developed thrombocytopenia with the appearance of symptoms such as purpura, fatigue, anorexia, and weight loss. Furthermore, clinical examinations revealed that she also had Addison's disease, rheumatoid arthritis, and autoimmune hematological diseases such as thrombocytopenia and hemolytic anemia. However, the cytopenia and all autoimmune disorders were remarkably improved after she received steroid therapy.
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PMID:Myelodysplastic syndrome accompanied by Addison's disease and multiple autoimmune phenomena: steroid therapy resolved cytopenias and all immune disorders. 1168 40

Addison's disease or primary adrenal insufficiency is a rare disease, which is usually caused by autoimmune destruction of the adrenal cortex. The clinical picture is caused by deficiency of cortisol and aldosterone. These deficiencies are accompanied by adrenal androgen depletion of yet unknown significance. The current therapy is the replacement of glucocorticoids and mineralocorticoids, but the available drugs do not restore the normal diurnal variations in serum hormone levels. The clinical consequences of the grossly unphysiological replacement therapy are largely unknown. Many patients with Addison's disease on standard replacement therapy complain of fatigue, weariness, and reduced stress tolerance. One particular concern has been negative effects on both bone metabolism due to over-replacement of glucocorticoids and androgen depletion. This review discusses the evidence for the current drug and dosage recommendations. Current recommended daily starting dose for hydrocortisone and cortisone acetate are 20 and 25 mg, respectively, divided into two or preferably three doses. The mineralocorticoid depletion should be treated with fludrocortisone 0.05-2.0 mg/day [DOSAGE ERROR CORRECTED]. Replacement of dehydroepiandrosterone 20-50 mg has been advocated in adrenal failure, but the evidence for benefit is weak.
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PMID:Replacement therapy in Addison's disease. 1464 Sep 13

This report describes a 52-year-old male patient with idiopathic Addison's disease presenting depression as a first symptom. His psychomotor inhibition, depressive mood, sleep disturbances, general fatigue, muscular pain, and arthralgia were considered to be due to intense work in a stressful environment. Neither his physician nor his orthopedist found any physical disease. Therefore, he was diagnosed with endogenous depression by a psychiatric clinic, and antidepressants were prescribed. Antidepressants were not sufficient for improving his symptoms, and he was admitted to our hospital. Endocrine blood examination revealed primary adrenocortical insufficiency. Treatment with glucocorticoid induced rapid improvement in both the psychiatric and physical symptoms. It is well known that psychiatric symptoms occur in the progressive stage of Addison's disease. At present, however, the occurrence of psychiatric symptoms is very rare, mainly because of a decrease in the incidence of this disease or an increase in mild cases. In addition, Addison's disease presenting with psychiatric features in the early stage has the tendency to be overlooked and misdiagnosed. Thus, we suggest the necessity of blood work for ACTH and cortisol in the field of psychiatry.
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PMID:[A case of Addison's disease presented with depression as a first symptom]. 1558 Aug 69

Porphyrias are metabolic disorders of heme biosynthesis, which encompass a broad range of symptoms and signs, neurologic, cutaneous or mixed. Because of lack of specificity and polymorphous clinical picture, porphyrias can mimic either neuropsychiatric, dermatologic, or gastrointestinal diseases. We present the case of a 58 years old man to whom clinical presentation suspicious of Addison's disease (melanoderma, fatigue, weight loss, intermittent abdominal pain) was the disguise of porphyria cutanea tarda. A general background of porphyrias and differential diagnosis with other forms of hepatic porphyria, as well as other causes of hyperpigmentation, are given. The clinician should be aware of the protean manifestations of porphyrias and include them in clinical judgment in various situations.
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PMID:Diagnostic traps in porphyria: case report and literature review. 1583 79

Three boys, aged 5, 11 and 14 years, were admitted due to vomiting, fatigue and dehydration, and a 10-year-old boy was admitted due to circulatory and respiratory insufficiency. Two had Addison's disease, one had a late presentation of congenital adrenal hypoplasia due to a DAX-1 mutation and in one adrenal insufficiency was the first manifestation ofadrenoleukodystrophia. The boys recovered after treatment. It is important to recognise the symptoms of adrenal insufficiency, because treatment can be life-saving. After the initial diagnosis the underlying pathology should be sought.
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PMID:[Primary adrenal insufficiency in children]. 1594 Sep 15

The symptoms of primary adrenocortical insufficiency (Addison's disease) such as fatigue, anorexia, hypotension and hyperpigmentation are similar to those of normal pregnancy. Addison's disease is rare and the diagnosis can easily be overlooked during pregnancy. The concentration of corticosteroid-binding globulin (CBG) and cortisol in serum as well as urinary free cortisol increase 2-3 times during pregnancy. Therefore, the reference ranges for nonpregnant persons cannot be used during pregnancy. The diagnosis of Addison's disease in pregnancy should be based on analysis of p-ACTH which remains within the reference range in normal pregnancy until delivery. A case of Addison's disease diagnosed during pregnancy is presented and it illustrates the diagnostic difficulties. In patients taking oral estrogen containing contraceptives, serum levels of CBG and cortisol also increase 2-3 times, making s-cortisol values difficult to interpret. Also in these patients, analysis of p-ACTH is of value when suspecting Addison's disease.
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PMID:[Addison disease during pregnancy--a diagnostic dilemma. Symptoms are similar to normal pregnancy problems]. 1604 55

Oral replacement of the near-total deficiency of dehydroepiandrosterone (DHEA) in patients with Addison's disease (adrenal insufficiency) enhances mood and well-being and reduces fatigue. We studied the immunological effects of 12 wk of oral DHEA treatment in ten patients with Addison's disease receiving their normal mineralo- and glucocorticoid hormone replacement. We found that baseline circulating regulatory T cells were reduced in Addison's disease patients compared to controls, a hitherto unrecognised defect in this disorder. Oral DHEA treatment had a bimodal effect on naturally occurring regulatory (CD4+CD25hiFoxP3+) T cells and lymphocyte FoxP3 expression. Oral DHEA replacement restored normal levels of regulatory T cells and led to increased FoxP3 expression. These effects were probably responsible for a suppression of constitutive cytokine expression following DHEA withdrawal. In contrast, oral DHEA treatment led to reduced FoxP3 expression induced by TCR engagement and so augmented the cytokine response, but without a bias towards the Th1 or Th2 phenotype. NK and NKT cell numbers fell during DHEA treatment, and homeostatic lymphocyte proliferation was increased. We conclude that DHEA replacement in Addison's disease has significant immunomodulatory properties and propose that it has a greater impact on the human immune system than would be expected from its classification as a dietary supplement.
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PMID:Dehydroepiandrosterone replacement in patients with Addison's disease has a bimodal effect on regulatory (CD4+CD25hi and CD4+FoxP3+) T cells. 1625 54


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