A patient with preclinical Cushing's syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma.
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We report a case of preclinical Cushing's syndrome in a 54-year-old male associated with bilateral adrenocortical tumours. Physical findings and general laboratory data were unremarkable except for mild hypertension (158/90 mmHg) and impaired glucose tolerance. Endocrinological evaluation revealed the presence of autonomous cortisol secretion including unsuppressible serum cortisol by 8 mg dexamethasone test (11 microg/dl), high serum DHEA-S (3580 ng/ml, normal: 400-3500) and increased urinary 17-KS excretion (31.0-35.8 mg/day, normal: 5.8-21.3). CT scan demonstrated the presence of tumours in both adrenals and bilateral adrenalectomy was subsequently performed. Histological examination of the resected specimens revealed an adrenocortical carcinoma on the right side and an adenoma on the left side with noticeable cortical atrophy in non-neoplastic adrenals. Immunohistochemical study of steroidogenic enzymes demonstrated that all the steroidogenic enzymes involved in cortisol biosynthesis were expressed in both right and left adrenal tumours. Enzymatic activities of 21, 17alpha, 18, 11beta-hydroxylases were detected in both right and left adrenals except for the absence of 11beta-hydroxylase activity in the left adrenal adenoma. Results of in vitro tissue steroidogenesis examined in short-term tissue culture of the specimens revealed no significant differences between carcinoma and adenoma in cortisol production, but the production of adrenal androgens in carcinoma was significantly higher than that in adenoma, which may indicate the importance of evaluating adrenal androgen levels in patients with adrenocortical neoplasms. (+info)
A case of renin-producing adrenocortical cancer.
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Here we report a case of a renin-producing adrenocortical carcinoma. A 57-year-old woman was referred to our hospital complaining of thirst and generalized muscle weakness. She was diagnosed as being hypertensive and diabetic with associated hypokalemia and she had a hard elastic mass with a diameter of 10 cm on the left side of her neck. An abdominal computed tomography scan revealed a suprarenal mass on the left side (8.5 x 8 x 6.5 cm). Endocrinological examination demonstrated a marked elevation in the patient's serum glucocorticoid and sex steroid hormones as well as plasma renin activity. Histological examination of a sample taken from the neck mass revealed a metastasis from an adrenal carcinoma, which was stained positively with antibodies against cytochrome P450 and renin, establishing the diagnosis of a renin-producing adrenocortical carcinoma. Trilostane was effective in reducing serum cortisol levels, but mitotane was ineffective. (+info)
Antiarrhythmic, haemodynamic and metabolic effects of 3alpha-amino-5alpha-androstan-2beta-ol-17-one hydrochloride in greyhounds following acute coronary artery ligation.
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1 The antiarrhythmic, haemodynamic and metabolic effects of a new amino steroid, ORG6001, have been investigated in experimental acute myocardial infarction in anaesthetized greyhounds. 2 ORG6001 administered either intravenously (2-10 mg/kg) or orally (50 mg/kg) significantly reduced the incidence of ventricular ectopic beats in the first 30 min after ligation of the left anterior descending coronary artery. 3 In dogs pretreated with ORG6001, metabolic changes indicative of myocardial ischaemia (lactate production and potassium efflux) were less marked than those occurring in control animals. 4 Antiarrhythmic doses of ORG6001 caused only minimal transient haemodynamic effects. 5 These results suggest that ORG6001 may possess distinct advantages over presently-used antiarrhythmic drugs in the prevention and treatment of the early arrhythmias which occur after myocardial infarction. (+info)
The biochemical study of intermaxillary fixation (IMF) stress in oral surgery inpatients.
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Although intermaxillary fixation (IMF) is performed to treat the patients with maxillary fracture, this procedure is very stressful to the patients. IMF has been reported to increase noradrenaline (NA) release in the brain and elevate plasma corticosterone contents in the rat. These changes were significantly attenuated by diazepam, an anxiolytic of the benzodiazepine family. These results suggest that IMF could greatly affect the pituitary-adrenal system as a stress. In the present study, in order to examine the influence of IMF on the human body function, we measured levels of 17-hydrocorticosteroids (17-OHCS) and 17-ketosteroid (17-KS), which are metabolites of the adreno-cortical hormone cortisol, in the urine of inpatients undergoing IMF. The subjects were requested to fill out a questionnaire on irritableness caused by IMF. In these patients, urinary 17-OHCS levels were significantly increased after IMF and well correlated to the results of the questionnaire. The finding suggested that urinary 17-OHCS levels reflect stress related to IMF, and that such stress mainly causes an irritated feeling. Natural killer cell activity (NK activity), which is considered to be related to stress, was measured in these patients. The relationship between 17-OHCS levels and NK activity was examined in reference to the results of the questionnaire. Questionnaire showed that most patients noted insomnia and an irritated feeling during IMF. To examine the influence of anxiolytic agents on stress related to IMF, an anxiolytic agent, ethyl loflazepate, was administered during IMF, and urinary 17-OHCS levels were measured. There was no correlation between 17-OHCS levels and NK activity in the patients. Furthermore, no correlation was observed between visual analogue scale (VSA) and NK activity. Increases in 17-OHCS levels in the group treated with ethyl loflazepate, an anxiolytic of the benzodiazepine family, were significantly lower than in the untreated group. This suggests that ethyl loflazepate reduced stress responses to IMF. It has been reported that NK activity is reduced inpatients with depression or chronic fatigue syndrome. However, NK activity may not be affected by mechanical stress such as IMF. The finding that an anxiolytic agent, ethyl loflazepate, inhibited stress responses to IMF further suggests that anxiolytic drugs are very useful for treatment of irritated feeling of the patients undergoing IMF. (+info)
Garlic supplementation increases testicular testosterone and decreases plasma corticosterone in rats fed a high protein diet.
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The effects of garlic supplementation on protein metabolism were investigated by measuring testis testosterone and plasma corticosterone in rats fed diets with different protein levels. In Experiment 1, rats were fed experimental diets with different protein levels (40, 25 or 10 g/100 g casein) with or without 0.8 g/100 g garlic powder. After 28 d of feeding, testosterone contents in the testis were significantly higher and plasma corticosterone concentrations were significantly lower in rats fed 40 and 25% casein diets with garlic powder than in those fed the same diets without garlic powder. Urinary excretion of 17-ketosteroid (an index of testosterone), nitrogen balance and hepatic arginase activity were significantly higher in rats fed the 40% casein diet with garlic powder than in the 40% casein controls. In Experiment 2, the effect of diallyldisulfide (a major volatile sulfur-containing compound in garlic) on the secretion of luteinizing hormone (LH) from the pituitary gland, which regulates testosterone production in the testis, was investigated in anesthetized rats. Plasma LH concentration increased dose dependently after administration of diallyldisulfide (P < 0.01, r = 0.558). These results suggest that dietary supplementation with 0.8 g/100 g garlic alters hormones associated with protein anabolism by increasing testicular testosterone and decreasing plasma corticosterone in rats fed a high protein diet. (+info)
Computerized multicuvette system for single substance and group analysis and for the chromatographic isolation and quantitation of compounds in complex mixtures.
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A new computer-interfaced system of general applicability in the clinical laboratory has been built. The system is constructed around a new type multicuvette. Quantitation is currently by spectrophotometry and is on-line, with use of a mini-computer with output going to an electrostatic printer/plotter. The system can be used for single-substance batch analyses, for group analyses, and for the estimation of profiles of compounds after preliminary high-resolution liquid chromatography tailored to interface with the multicuvette. (+info)
Involvement of the cholinergic pathway in the pathogenesis of pituitary Cushing's syndrome.
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Transsphenoidal adenomectomy is currently the first choice for treatment of patients with pituitary ACTH-dependent Cushing's syndrome. However, pharmacotherapy is prescribed for some patients, e.g., unsuccessful surgery. We treated a woman in whom pituitary Cushing's syndrome was improved while she was on antimuscarinic cholinergic agents, atropine sulphate and pirenzepine hydrochloride. The diminished effect of anticholinergics on ACTH and cortisol was incidentally identified in an inferior petrosal sinus sampling procedure. A single intramuscular injection of atropine significantly decreased both ACTH (43.9 pg/ml to less than 12.0; normal, 12.0-40.0 pg/ml) and cortisol (29.9 microg/dl to 13.6; normal, 7.6-23.6 microg/dl). An M1-muscarinic receptor specific antagonist, pirenzepine hydrochloride, also had a diminishing effect on these hormones and this inhibiting effect was partially blocked by the simultaneous administration of an anticholinesterase agent, pyridostigmine bromide. Chronic oral ingestion of these agents led to improvement in clinical symptoms, and urinary 17-hydroxycorticosteroid and 17-ketosteroid levels were at normal to upper-normal levels. This is the first documentation of involvement of the cholinergic system in the pathogenesis of pituitary Cushing's syndrome. (+info)
Micro-analytical identification, by NMR, of elevated steroid in urine of Cushing's syndrome patients.
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We previously reported that the daily urinary unidentified ketosteroid glucuronide (US-G) level in patients with Cushing's syndrome was much higher than that in the healthy subjects. Furthermore, urine samples from patients with Cushing's syndrome, including those with pituitary adenoma and adrenal adenoma, yielded almost the same high excretion levels, despite the different sites of the adenomas. We extracted US obtained by hydrolysis of US-G in urine of patients with Cushing's syndrome, purified it, and analyzed its chemical structure. Molecular weight and molecular formula were analyzed by MS spectrometry, and the chemical structure was analyzed by NMR spectrometry, utilizing small quantities of refined US. The substance has a molecular weight of 304 Da, a molecular formula of C19H28O3, and its chemical structure is 3alpha,11beta-dihydroxyandrost-4-en-17-one. (+info)