Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

African sleeping sickness (SS) is a severe, potentially lethal parasitic disease. The treatments of choice are the antiparasitic agents suramin, which is adrenotoxic, and/or melarsoprol. We evaluated the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis of patients with SS before, during, and after therapy with suramin and/or melarsoprol, in two sequential stages. First, we employed the standard adrenocorticotropic hormone (ACTH) 1-24 stimulation test (250 micrograms i.v.) to assess the maximal adrenocortical responsiveness of 69 patients with SS and 38 normal controls. We demonstrated paradoxically subnormal cortisol responses before suramin therapy [net cortisol response 60 min after stimulation: 10.5 +/- 2.9 (mean +/- SE) vs. 17.5 +/- 1.0 micrograms/dl for controls, p = 0.004], with 27% of the patients falling within the adrenal insufficiency range (stimulated cortisol concentration < 20 micrograms/dl). These responses subsequently and unexpectedly improved with suramin and/or melarsoprol therapy. Second, we performed a human corticotropin-releasing hormone (hCRH) test (100 micrograms i.v.) in 68 additional patients with SS and 14 control subjects to examine whether the glucocorticoid deficiency observed was primary and/or secondary. Compared to controls, the ACTH and cortisol responses to hCRH were blunted (ACTH after 60 min: 29 +/- 7 vs. 58 +/- 8 pg/ml in controls, p = 0.014; cortisol: 15.2 +/- 1.5 vs. 19.6 +/- 0.7 micrograms/dl, p = 0.018), suggesting the presence of secondary adrenal insufficiency. There was improvement of both ACTH and cortisol responsiveness to hCRH with therapy, with cortisol recovery occurring before ACTH, suggesting an additional primary component of adrenal dysfunction in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impairment of adrenocortical function associated with increased plasma tumor necrosis factor-alpha and interleukin-6 concentrations in African trypanosomiasis. 852 79

There is increasing evidence that cytokines contribute to the immunopathogenesis of human immunodeficiency virus (HIV) infection. It may be, therefore, that compensatory rises in circulating cytokine antagonists also occur in HIV infection and that such changes mark disease progression. To test this idea, plasma concentrations of the cytokine antagonists alpha-melanocyte-stimulating hormone (alpha-MSH), interleukin-1 receptor antagonist (IL-1ra), and soluble tumor necrosis factor receptor (sTNFr) were measured in patients of different Centers for Disease Control (CDC) categories of HIV infection and in seronegative controls. Plasma levels of all these cytokine antagonists were higher in HIV-infected patients. IL-1ra and sTNFr concentrations were correlated with indicators of disease activity: positively with plasma neopterin and negatively with CD4+ T lymphocyte counts. alpha-MSH and sTNF r were greater in CDC groups III and IV, whereas IL-1ra was elevated only in the latter group. Because cytokines activate the hypothalamic-pituitary-adrenal axis and adrenal steroids inhibit cytokine production, we measured circulating adrenocorticotropic hormone (ACTH) and cortisol in HIV-infected patients and investigated relations among these hormones, cytokine antagonists, and markers of disease progression. It appears that these physiological modulators of cytokine activity are not closely linked to sTNFr, IL-1ra and alpha-MSH: there were no significant correlations between plasma concentrations of ACTH or cortisol and those of cytokine antagonists, nor were there correlations between hormones and markers of disease progression such as neopterin or CD4+ T cell counts. It is notable that severe adrenal insufficiency was extremely rare (3%) in HIV-infected patients; it was confined to the AIDS group and was consistently secondary to ACTH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma concentration of cytokine antagonists in patients with HIV infection. 852 84

The reported number of adrenal incidentalomas has been increasing because of wider application of imaging techniques. Patients with asymptomatic cortisol producing adrenal adenoma (ASCA) which secretes cortisol without clinical evidence of Cushing's syndrome has been more frequently observed than previously assumed, and they have a risk of adrenal insufficiency after adrenalectomy. Therefore patients with incidentalomas should be screened for cortisol overproduction. The aim of this study is to discover an easy screening test to uncover ASCA. We investigated the hormone profiles of 4 patients with ASCA in comparison with 11 patients with non-functional adrenal tumor and 10 patients with adrenal Cushing's syndrome. We also investigated the expression of dehydroepiandrosterone sulfotransferase (DHEA-ST) in surgically removed attached non-neoplastic adrenal tissues by immunostaining, which was considered to represent the degree of suppression of the hypothalamo-pituitary-adrenal axis. Serum dehydroepiandrosterone sulfate (DHEA-S) levels of all the patients with ASCA and adrenal Cushing's syndrome were lower than those of healthy subjects of corresponding age, but they were within the normal range in the patients with non-functional adrenal tumors. The serum DHEA-S level reflects the degree of suppression of the normal adrenal gland by cortisol hypersecretion from adrenal tumors. But the serum level of DHEA-S decreases with age, and because the normal range of serum DHEA-S is low in elderly subjects, we should be careful to evaluate the level of DHEA-S in elderly patients with adrenal Cushing's syndrome or ASCA. The immunohistochemical study showed DHEA-ST expression was noticeably suppressed in the adjacent adrenal cortex in ASCA and adrenal Cushing's syndrome. The decreased expression of DHEA-ST may reflect autonomous neoplastic cortisol secretion and subsequent ACTH suppression in ASCA and adrenal Cushing's syndrome. A single measurement of plasma ACTH or measurement of ACTH response to corticotropin-releasing hormone was not enough to screen for ASCA because of the wide variation among the cases. Dexamethasone suppression test is essential in identifying ASCA and also a single determination of serum DHEA-S is easy and may be useful for the screening of ASCA in adrenal incidentalomas in young and middle aged subjects, and is especially useful for outpatients.
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PMID:Serum levels of dehydroepiandrosterone sulfate in patients with asymptomatic cortisol producing adrenal adenoma: comparison with adrenal Cushing's syndrome and non-functional adrenal tumor. 893 May 26

The triple A or Allgrove's syndrome (MIM*231550) is an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. Since its first description by Allgrove et al. (1978) more than 70 cases from all over the world have been reported. The syndrome manifests itself during the first decade of life with severe hypoglycaemic episodes which can cause sudden death. The frequent association with neurological disorders presenting as a mixed pattern of upper and lower motor neuropathy, sensory impairment, autonomic neuropathy and mental retardation may result in a severely disabling disease. As an additional feature some patients have hyperkeratosis of their palms and soles. We have performed a systematic genome linkage scan in eight triple A families of which three were consanguineous [including the large highly inbred kindred described by Moore et al. (1991)]. We obtained conclusive evidence for linkage of the triple A syndrome locus to markers on chromosome 12q13 (D12S368, theta max = 0, Zmax = 10.81) with no indication of genetic heterogeneity. Haplotype and multipoint analyses suggest that the gene is located on a chromosomal segment flanked by the markers D12S1629 and D12S312 which are 6 cM apart. This region harbors the type II keratin gene cluster, and potential candidate genes include SCN8A and HOXC genes.
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PMID:Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster. 896 64

Neurohypophyseal function was studied by hypertonic saline infusion with plasma vasopressin measurement in 3 patients with adrenal insufficiency before and after cortisol replacement. Although each patient had different causes of adrenal insufficiency, all showed impaired water excretion before replacement. The first patient with isolated adrenocorticotropin deficiency had marked hyponatremia and inappropriate vasopressin secretion which was normalized after replacement, indicating vasopressin hypersecretion during hypoadrenocorticism. The second patient had combined anterior and posterior pituitary deficiency due to postpartum hypopituitarism and showed completely absent vasopressin secretion, with her polyuria being masked before cortisol replacement, suggesting a vasopressin-independent intrarenal mechanism of antidiuresis. The third patient with panhypopituitarism due to a pituitary tumor also had preexisting diabetes insipidus with defective vasopressin secretion. In this case, however, plasma vasopressin was found to be elevated when adrenal insufficiency and hyponatremia subsequently developed. Together, these results indicate that vasopressin hypersecretion does occur during adrenal insufficiency, but that the accompanying urinary diluting defect may be attributable either to vasopressin-dependent or to vasopressin-independent mechanisms.
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PMID:Osmoregulation of plasma vasopressin in three cases with adrenal insufficiency of diverse etiologies. 901 Jul 16

Ketoconazole is an orally active imidazole derivative that is an effective therapeutic drug in the treatment of mycotic infection. The development of gynecomastia in male patients treated with ketoconazole has led to investigation of its potent inhibitory effect on adrenal steroidogenesis. In this study, we present our preliminary experience using high dose ketoconazole, which was used safely as a palliative treatment in 3 patients with Cushing's syndrome prior to surgery. The 24-hour urinary free cortisol excretion was decreased by more than 52% in 1 to 2 days and fell to within normal limits of less than 120 micrograms by the 1st day, 2nd day or 15th day in these 3 patients. Cushing's syndrome was either adrenocorticotropin-dependent or -independent during treatment. In case 3, the plasma adrenocorticotropin level was unchanged during treatment in the first week, despite marked reductions in plasma and 24-hour urinary free cortisol levels. The most significant improvement of clinical symptoms was that the patients could sleep much more comfortably at night following the suppression of hypercortisolism by ketoconazole. Monitoring of liver function and addition of dexamethasone are recommended to prevent the possibility of reversible adverse effects such as severe hepatic injury and adrenal insufficiency or even crisis.
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PMID:The effect of ketoconazole in pre-operative treatment in Cushing's syndrome: three cases report. 904 68

Primary adrenal insufficiency (PAI) is a relatively rare but serious condition that can lead to signs and symptoms ranging from mild generalized weakness and fatigue to fulminant shock and death. We present the case of a previously healthy 31-year-old man who developed PAI while undergoing rehabilitation after a severe traumatic brain injury (TBI). The patient suffered a TBI with comminuted skull fractures, bifrontal confusions, and bilateral epidural hematomas in a jet-ski accident. Acute hospitalization was prolonged by several medical complications, and the patient was admitted for subacute rehabilitation 1 month after his injury with cognitive deficits, persistent agitation, confusion, generalized weakness, and poor endurance for therapy. His weakness, fatigue, and orthostasis did not improve with attempts at gradual remobilization. The patient also had persistent anorexia, nausea, and hyponatremia despite various treatment regimens. Endocrinology workup showed normal anterior pituitary function but an abnormal response to adrenocorticotropic hormone (ACTH) stimulation, leading to the diagnosis of PAI. The patient was treated with prednisone and fludrocortisone, which resulted in improvement in clinical symptoms followed by rapid gains in all functional areas. No previous descriptions of PAI following head injury were found in the medical literature. It is important for physiatrists to be aware of this entity because symptoms of adrenal insufficiency can be similar to those commonly seen with TBI alone. PAI may also be confused with other endocrine disorders more frequently seen after TBI such as the syndrome of inappropriate antidiuretic hormone secretion. Recognition and appropriate management of adrenal insufficiency can lead to significant clinical and functional gains.
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PMID:Primary adrenal insufficiency following traumatic brain injury: a case report and review of the literature. 908 56

Morphine is suggested to influence immune function by activation of hypothalamic-pituitary-adrenal axis. Thus, we investigated 8 pain patients prior to and during prolonged oral treatment with 30-240 mg of sustained release morphine for plasma concentrations of adrenocorticotropic hormone and serum concentrations of cortisol. Results revealed that pain patients at basal status had elevated cortisol concentrations. Hormone concentrations measured after 1, 4 and 12 weeks of morphine treatment were significantly decreased, not normalized, but at very low values. Since these data, even in the absence of clinical symptoms, might have been indicative for adrenal insufficiency, a corticotropin-releasing hormone test was performed in 2 patients. After injection of 100 micrograms of human corticotropin-releasing hormone. ACTH and cortisol concentrations increased sufficiently. In conclusion, even though low hormonal concentrations were observed in pain patients during morphine treatment, pituitary and adrenal stimulation of the endocrine axis remained intact.
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PMID:Effects of oral treatment with sustained release morphine tablets on hypothalamic-pituitary-adrenal axis. 922 53

We present two patients with manifest acquired immunodeficiency syndrome (AIDS) suffering from a generalized cytomegalovirus (CMV) infection. Over the course of several weeks they had developed a state of increasing lethargy and fatigue and one patient had noticed a darkening of his skin. These and other symptoms (vomiting, diarrhoea, hypotension) were suggestive of adrenal insufficiency. Laboratory findings included an increase of serum potassium levels, a decrease of serum sodium concentrations and elevated levels of the adrenocorticotropic hormone (ACTH). These findings, as well as the prompt therapeutic response to hydrocortisone established the diagnosis of adrenal insufficiency. Although definitive proof is lacking, generalised CMV infection is the most likely cause of our patients' symptoms. For the early initiation of appropriate substitution therapy, persons infected with the human immunodeficiency virus (HIV) with signs of CMV infection should be carefully and repeatedly monitored for clinical and laboratory signs of adrenal insufficiency.
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PMID:Primary adrenal insufficiency in two patients with the acquired immunodeficiency syndrome associated with disseminated cytomegaloviral infection. 940 82

Tetracosactin [corticotropin-(1-24)] is used for clinical testing of adrenocortical responsiveness. The usual dose [high dose test (HDT)] is 250 micrograms. With this test, patients with mild secondary adrenal insufficiency are usually not identified, thus putting them at risk of an adrenal crisis in stressful situations. It was recently reported that a tetracosactin test with approximately 1 micrograms [low dose test (LDT)] identifies patients with mild forms of pituitary-adrenal insufficiency. We performed both the HDT and the LDT in 35 control subjects and in 44 patients with pituitary disease, mostly pituitary tumors. In these patients, more sensitive reference tests for evaluating the pituitary-adrenal axis (insulin-induced hypoglycemia, metyrapone, and CRH tests) were also performed. In the HDT, plasma cortisol was measured 30 and 60 min after tetracosactin injection; in the LDT (0.5 microgram/m2 body surface area), plasma cortisol was measured 20, 30, 40, 50, and 60 min postinjection. In 6 control subjects, tetracosactin plasma levels were also measured after injection. In the HDT, the correlation between 30 and 60 min cortisol levels was extremely high (r = 0.991; P < 0.0001), but the correlation of the LDT with the HDT at 30 min was also highly significant (r = 0.948; P < 0.0001). The lower normal limit of cortisol responses (means of controls minus 2 SD) at 30 min was lower in the LDT by 3.1 micrograms/dL (85 nmol/L) than in the HDT. Compared with the reference tests, the diagnostic sensitivities of the HDT and the LDT were almost identical. Both tests identified patients with moderately to severely pathological insulin and metyrapone tests, but not those with slightly pathological reference tests. In the HDT, plasma tetracosactin rose to more than 60,000 pg/mL shortly after injection. In the LDT, it rose to 1,900 pg/mL. Both concentrations stimulate cortisol (supra-) maximally. Together, these data show that in pituitary disorders the results of the LDT and the HDT are almost identical. Plasma tetracosactin levels in the LDT still rise to levels that maximally stimulate the adrenal. Tetracosactin testing with low or high doses cannot generally replace the more expensive and cumbersome insulin or metyrapone tests.
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PMID:Comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease. 1002 66


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