Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004093 (asthenia)
 2,650 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of cyproterone acetate (CA) administration on the pituitary-adrenal axis were studied in 30 hirsute females. The patients were treated continuously with a daily dose of 100 mg of CA for a maximal period of 12 months. Insulin-induced hypoglycaemia and ACTH infusion were performed on pre-treatment conditions and after 1, 4, 6 and 12 months of CA treatment. From a clinical point of view, a dramatic improvement of hirsutism was evident after 6 months of therapy. The most commonly reported side effects were amenorrhoea and transient uterine haemorrhage. Apart from asthenia, no symptoms of adrenal insufficiency were noticed. No changes in pituitary-adrenal secretion were observed during the first 4 months of therapy. From the 6th month, a reduction in basal as well as stimulated cortisol levels was seen. Simultaneously, an enhanced ACTH response to hypoglycaemia was observed. Both effects became more pronounced after 1 year of treatment. There were no significant changes in ACTH basal values. Six months after discontinuation of the drug, adrenocortical reserve improved but was still slightly reduced when compared to pre-treatment range at that time. These findings suggest a time-dependent negative effect of CA on adrenal steroidogenesis which shows a reversible character 6 months after antiandrogen withdrawal. Therefore, steroid cover should be considered for intercurrent illness in patients treated for longer than 6 months with this therapeutic regime.
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PMID:Time dependency and reversibility of the effects of exclusive cyproterone acetate therapy on pituitary adrenal function in hirsute women. 299 29

The paper describes the case of a 38 year's old alcoholic patient. The investigation of his severe asthenia led to the discovery of an isolated ACTH deficiency: plasma cortisol was less than 1 microgram 100 ml reactivable by tetracosa-peptide beta 1-24. Plasma ACTH was low and remained so after LVD and metyrapone. Persistent leuconeutropenia without myelogram and agar cultures abnormalities was noted. Etiocholanolone test was negative and epinephrine induced a significant rise in blood leucocytes. The authors review the mechanisms of corticoid action on leucopoiesis. After 10 months corticoid treatment, leuconeutropenia improved but was still present suggesting an other underlying mechanism than cortisol insufficiency per se.
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PMID:[Isolated ACTH deficiency associated with leukoneutropenia (author's transl)]. 628 92

Out of a great number of cases with chronic psychoorganic syndrome studied by us, we have selected, for investigation, a number of 100 cases which presented common symptomatology: a psychosyndrome showing, by a large number of manifestations such as asthenia, fatigability, adynamia with various degrees of intensity building up to reaction latency, diminution or even absence of initiative, basic-negativism, tendency to depression with feeling of futility, anxiety, lowered affective tonus. The intellectual activity is largely diminished, the stream of ideas is poor, and there is a limited domain of preoccupations. All these symptoms alongside with somatic, muscular, renal, respiratory, digestive and cardiovascular disorders have led us to the hypothesis of chronic deficiency of the hormones in the adrenal glands. The adrenal glands have been studied by indirect exploration of the hydroelectrolytic metabolism of the peripheral blood, the Thorn test and the Robinson-Power-Kepler test. For the exploration of the glucocorticoids, a basal test has been used such as the 17-hydroxycorticoid test, which measures cortisol elimination, or as the 11-desoxycorticosteroids and metabolites, or the colorimetric Porter-Silber method. Among the dynamic tests, we have used stimulating tests, the ACTH test (synthetic Synachtene), which measures cortisolemia and the 17-urinary corticosteroids, faster and easier than the Thorn test. In order to assess androgens, we have used the ACTH deposit dynamic test (Synachtene retard), which in the case of normal function of the adrenal glands, in 24 hours, doubles the elimination of 17-hydrocorticosteroids, 17-Ketosteroids, D. H. E. A., pregnandiol, pregnantriol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Study on physiopathology of the chronic psychoorganic syndrome. Investigation on the reactivity of the adrenal glands in patients with psychoorganic chronic. 798 17

Both hypo- and hyperkalemic periodic paralysis may be difficult to diagnose conclusively when patients are not seen during attacks. Since paralysis of both types can be induced with ACTH, we have determined the frequency of this response in small groups of patients. Weakness or paralysis with appropriate changes in serum K concentration resulted from ACTH gel administration, in 4 of 5 patients with known hypokalemic periodic paralysis and in 3 of 3 patients with hyperkalemic paralysis. No adverse effects of the test were observed, but hospitalization and careful monitoring were necessary. The response to ACTH appears to be a sensitive, useful aid to the diagnosis of both hypo- and hyperkalemic periodic paralysis.
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PMID:Use of corticotropin-induced potassium changes in the diagnosis of both hypo- and hyperkalemic periodic paralysis. 838 12

Myasthenia gravis, a neuromuscular junction autoimmune disease, may be associated to glandular autoimmune diseases such as adrenalitis. We report here the association of myasthenia gravis with a rare cause of adrenocortical deficiency, i.e. isolated corticotroph deficiency. The patient suffered from myasthenia gravis for 5 yr when she reported increased asthenia. Basal cortisol and ACTH levels were low. Metyrapone failed to increase ACTH and 11-desoxycortisol. Corticotropin-releasing hormone or tetracosactide failed to increase normally the cortisol levels. No other endocrine dysfunction or autoimmune disease could be detected. This observation enlarges the spectrum of endocrine diseases associated to myasthenia gravis and strengthens the need for careful endocrine examination.
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PMID:Isolated corticotroph insufficiency associated to myasthenia gravis. 949 6

Corticosteroid-binding globulin (CBG) is the plasma transport protein that regulates the access of glucocorticoid hormones to target cells. Genetic deficiencies of CBG are rare, and only a single human CBG variant (Trancortin Leuven) has been related so far to decreased cortisol-binding affinity. We report here on a 43-yr-old woman, referred for chronic asthenia and hypotension, with repeatedly low morning serum cortisol levels (22-61 nmol/L; normal range, 204-546 nmol/L), normal plasma ACTH levels (38-49 pg/mL; normal, <50 pg/mL), and normal urinary cortisol (10-76 nmol/24 h; normal range, 10-105 nmol/24 h). An increased percent-free (dialysable fraction) serum cortisol (8.7-9.7%, normal range, 2.9-3.9%) suggested abnormal CBG binding activity. Indeed, she had a low serum CBG concentration (24 mg/L vs. 44+/-6 mg/L in normal women), and the affinity of her CBG for cortisol was decreased (association constant, Ka = 0.12 L/nmol vs. 0.82+/-0.29 L/nmol). In her immediate family members, the serum CBG concentration and cortisol-binding activity were normal in her husband, but the four living children had slightly lower serum CBG concentrations than the reference ranges for their pre- and postpubertal status. Measurements of cortisol distribution in undiluted serum indicated that an increase in the percentage of nonprotein-bound cortisol offsets the low cortisol levels to give approximately normal concentrations of free cortisol in serum. Direct sequencing of PCR-amplified exons encoding CBG revealed that the proband was homozygous for a polymorphism (GAC-AAC) in the codon for residue 367, which results in a Asp367-->Asn substitution. Her children were heterozygous for this polymorphism. When this nucleotide change was introduced into a normal human CBG complementary DNA, for expression in Chinese hamster ovary cells, Scatchard analysis demonstrated that the Asn367 substitution reduced the affinity of human CBG for cortisol by approximately 4-fold (Ka = 0.15 L/nmol), as compared to normal recombinant CBG (Ka = 0.66 L/nmol). These results suggest that Asp367 is an important determinant of CBG steroid-binding activity and that normal negative regulation of the hypothalamic-pituitary-adrenal axis is maintained by relatively normal serum-free cortisol concentrations, despite a marked reduction in the steroid-binding affinity of this novel human CBG variant, which we have designated as CBG-Lyon.
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PMID:Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity. 1063 11

Familial isolated glucocorticoid deficiency is a form of potentially lethal hereditary unresponsiveness to ACTH that manifests as primary adrenal insufficiency, usually without mineralocorticoid deficiency. Affected children commonly present with hyperpigmentation, recurrent hypoglycemia, chronic asthenia and failure to thrive within the first 2 years of life. Typically, they have deficient production of cortisol and adrenal androgens in the presence of markedly elevated ACTH levels, while renin and aldosterone levels are usually normal and responsive to activation of the renin-angiotensin axis. Clinical awareness of these syndromes is of considerable prognostic and therapeutic importance. The etiological involvement of the ACTH receptor gene in isolated glucocorticoid deficiency has been recently established in many, but not all, affected families. Several naturally occurring mutations of the ACTH receptor gene have been identified to date and have helped illuminate the mechanisms of ligand binding and signal transduction by this receptor. Discovery of the molecular defect(s) responsible for isolated glucocorticoid deficiency in cases with a normal ACTH receptor gene coding region and for the triple A syndrome (adrenal insufficiency, alacrima, achalasia) will hopefully provide further insight into the mechanisms of adrenocortical function and will increase the prospect of new therapeutic approaches.
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PMID:Isolated glucocorticoid deficiency and ACTH receptor mutations. 1071 60

To describe the clinical and immunologic characteristics of patients with adrenal involvement and antiphospholipid syndrome (APS), we conducted a computer-assisted (PubMed) search of the literature to identify all cases of primary adrenal insufficiency associated with antiphospholipid antibodies published in English, French, and Spanish from 1983 (when APS was first defined) through March 2002. We reviewed 86 patients (80 from the literature plus 6 from our cohort); 55% were male, and the mean age at presentation was 43 +/- 16 years. Sixty-one (71%) patients had primary APS, and 14 (16%) had systemic lupus erythematosus. In 31 (36%) patients, adrenal insufficiency was the first clinical manifestation of APS. Abdominal pain was present in 55% of patients, followed by hypotension (54%), fever (40%), nausea or vomiting (31%), weakness or fatigue (31%), and lethargy or altered mental status (19%). The main finding in imaging techniques was compatible with adrenal hemorrhage (59%) and in histopathologic study was a hemorrhagic infarction with vessel thrombosis (55%). Lupus anticoagulant was detected in 97% of patients and the anticardiolipin antibodies titer was positive in 93% of patients. Most patients (95%) were positive for the IgG isotype of anticardiolipin antibodies, whereas 40% were positive for the IgM isotype. Baseline cortisol levels were decreased in 98% of patients, ACTH hormone levels were increased in 96% of patients, and the cosyntropin stimulation test was positive in 100% of patients tested. Steroid replacement therapy was the most frequent treatment (84%), followed by anticoagulation (52%) and aspirin (6%). Thirty-two of 35 (91%) patients with prolonged anticoagulant therapy were in good health with a mean follow-up of 25 months, whereas 25 of the 69 (36%) patients with outcome data available had died. The results of the present review stress the clinical importance of systematic screening for lupus anticoagulant and anticardiolipin antibodies in all cases of adrenal hemorrhage or infarction. An initial screening for hypoadrenalism is mandatory in any antiphospholipid antibody-positive patient who complains of abdominal pain and undue weakness or asthenia.
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PMID:Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients. 1264 Jan 87

To explore the relationship between pituitary morphology and function, we performed mid-sagittal MRI and endocrinological evaluation in 38 patients with asthenia. Six patients were diagnosed as having complete empty sella (ES) and 16 patients partial empty sella (PES). BMI, blood pressure, serum Na, ACTH, cortisol, TSH and T(4) were lower in ES group and PES group than in the group with normal pituitary size. Age in the patients with ES was oldest. Multiple regression analysis revealed that serum cortisol level was independently correlated with the size of the pituitary (beta = 0.586, p = 0.0069). Other variables, including age, BMI, blood pressure, serum Na, ACTH, TSH and T(4), were not correlated with the pituitary size when multivariate analysis was employed. In conclusion, there is a close relationship between the reduction of size of pituitary gland and the degree of adrenocortical dysfunction in asthenic patients. It is suggested that the pituitary-adrenal axis is especially vulnerable in empty sella syndrome, and therefore, meticulous evaluation of the hypophysial adrenal axis is recommended in subjects with reduced pituitary size even in elderly population.
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PMID:Correlation between the pituitary size and function in patients with asthenia. 1612 12

Isolated ACTH deficiency (IAD) is a rare disorder, characterized by secondary adrenal insufficiency (AI) with low or absent cortisol production, normal secretion of pituitary hormones other than ACTH and the absence of structural pituitary defects. In adults, IAD may appear after a traumatic injury or a lymphocytic hypophysitis, the latter possibly due to autoimmune etiology. Conversely, a genetic origin may come into play in neonatal or childhood IAD. Patients with IAD usually fare relatively well during unstressed periods until intervening events spark off an acute adrenal crisis presenting with non specific symptoms, such as asthenia, anorexia, unintentional weight loss and tendency towards hypoglycemia. Blood chemistry may reveal mild hypoglycemia, hyponatremia and normal-high potassium levels, mild anemia, lymphocytosis and eosinophilia. Morning serum cortisol below 3 microg/dl are virtually diagnostic for adrenal insufficiency. whereas cortisol values comprised between 5-18 microg/dl require additional investigations: insulin tolerance test (ITT) is considered the gold standard but-when contraindicated-high or low dose-ACTH stimulation test with serum cortisol determination provides a viable alternative. Plasma ACTH concentration and prolonged ACTH infusion test are useful in differential diagnosis between primary and secondary adrenal insufficiency. For some patients with mild, near-to-asymptomatic disease, glucocorticoid replacement therapy may not be required except during stressful events; for symptomatic patients, replacement doses i.e., mean daily dose 20 mg (0.30 mg/kg) hydrocortisone or 25 mg (0.35 mg/kg) cortisone acetate, are usually sufficient. Administration of mineralocorticoids is generally not necessary as their production is maintained.
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PMID:Isolated corticotrophin deficiency. 1707 49


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