On the meaning of low-dose ACTH(1-24) tests to assess functionality of the hypothalamic-pituitary-adrenal axis.
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To analyse further the ACTH(1-24) low-dose test, which is of clinical interest, we have examined the dose-response relationship between plasma ACTH(1-24) and cortisol concentrations after i.v. administration of increasing doses (1, 5 or 250 microg) of ACTH(1-24) as a bolus. In addition, we have measured plasma ACTH(1-39) and cortisol levels after an insulin tolerance test (ITT). Although there was a dose response relationship between plasma ACTH(1-24) immunoreactivity and the dose injected, cortisol peaks were comparable, but lower than those reached after an ITT. Under these experimental conditions, an increase in plasma ACTH as low as 13 pmol/l (i.e. the increase obtained with the 1 microg dose) induced a near maximal cortisol response. Following injection of 1 microg ACTH(1-24), peak ACTH values were short lasting, similar to physiological daily bursts. After injection of 5 microg ACTH(1-24), plasma ACTH concentrations were higher than those reached during an ITT, but clearly shorter lasting. Injection of 250 microg ACTH(1-24) induced strikingly supraphysiological levels of plasma ACTH. We conclude that neither regular nor low-dose ACTH tests can fully reproduce the ITT. Our observations strongly suggest that the low-dose ACTH(1-24) test (1 microg) can be useful to estimate the adrenal sensitivity under basal, physiological conditions. (+info)
Nonchromatographic radioimmunoassay of plasma 11-deoxycortisol, for use in the metyrapone test, with polyethylene glycol as the precipant.
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We have developed a simple, reliable radioimmunoassay for plasma 11-deoxycortisol. The method does not require chromatography but instead makes use of a simple extraction procedure which, in combination with the antibody characteristics, is highly specific for the metyrapone test. Polyethylene glycol was used to separate free and antibody-bound steroid. The smallest amount measurable is 15 pg (2.0 mug/liter of plasma). The method is shown to be precise and accurate. Intraassay precision of the method for two plasma pools was 26.7 plus or minus 2.5 mug/liter (CV equals 9.4%) and 61.2 plus or minus 3.7 mug/liter (CV equals 6.0%). The respective inter-assay precision was 27.0 plus or minus 1.7 mug/liter (CV equals 6.3%) and 59.9 plus or minus 2.3 mug/liter (CV equals 3.8%). The validity of the assay was further verified by evaluating the plasma 11-deoxycortisol response to metyrapone administration. The relative simplicity of the method and the commercial availability of all reagents, including antisera, makes this radioimmunoassay procedure practical for use in clinical laboratories. (+info)
Cushing's syndrome and pituitary-adrenal suppression due to clobetasol propionate.
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Widespread application of clobetasol propionate resulted in suppression of the hypothalamic pituitary axis in four patients. Three patients showed Cushigoid features and developed symptoms of adrenocortical insufficiency on withdrawal of clobetasol. (+info)
Low-dose adrenocorticotropin test in patients with the acquired immunodeficiency syndrome.
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Adrenocortical insufficiency is a serious complication of AIDS. Usually, integrity of the hypothalamo-pituitary-adrenal (HPA) axis in AIDS patients is assessed by measuring basal cortisol levels and cortisol response to 250 microg of ACTH. Recent studies suggest that a lower ACTH dose increases the sensitivity of the procedure. In the present study, we investigated the prevalence of adrenal hypofunction in AIDS patients using a low-dose ACTH test (1 microg), evaluated the clinical characteristics that might suggest this diagnosis, and the diseases and/or drugs that could be associated with it. We prospectively evaluated 63 very ill AIDS patients and 16 normal controls. A standard examination assessed the presence of signs and symptoms of adrenal insufficiency. Blood samples were collected before and 30 and 40 minutes after an injection of 1 microg 1-24 ACTH. No opportunistic disease, signs, symptoms or drugs were associated with an abnormal cortisol response to ACTH. The lowest stimulated cortisol level in the control group was 18.5 microg/dL; cortisol levels > or = 18 microg/dL were taken to indicate a normal HPA axis. Test results revealed that 12/63 AIDS patients (19%) had an abnormal HPA axis. With these data in mind, we suggest a prospective adrenal function evaluation of all severely ill AIDS patients. (+info)
Clobetasone butyrate, a new topical corticosteroid: clinical activity and effects on pituitary-adrenal axis function and model of epidermal atrophy.
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Clobetasone butyrate is a new corticosteroid, selected for study because of its combination of good activity in the vasoconstriction test and low systemic activity in animals. Formulated as an 0.05% ointment and cream (Molivate) it was clinically effective in patients with eczema, its activity being significantly greater than that of hydrocortisone 1% or fluocortolone 0.2% (Ultradil). Under conditions that predispose to maximal percutaneous absorption clobetasone butyrate ointment had minimal effect on hypothalamic-pituitary-adrenal function. In an animal model of cutaneous atrophy it caused less thinning of the epidermis than steroids other than hydrocortisone. Clobetasone butyrate 0.05% ointment and cream gave every indication of offering clinically effective topical anti-inflammatory activity with a wide margin of safety. (+info)
Cushing's syndrome with a large pituitary adenoma producing both corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH).
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A 57-year-old man showed high serum cortisol, plasma adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) levels with a large pituitary tumor and a prostatic cancer. High dose dexamethasone did not suppress cortisol secretion and CRH administration did not stimulate cortisol secretion. After surgical removal of the pituitary tumor, plasma CRH, ACTH and serum cortisol levels were normalized. Histological examinations showed pituitary adenoma and prostatic adenocarcinoma, and pituitary adenoma was stained with both anti-CRH and anti-ACTH antibodies, but prostatic cancer was not stained. A CRH-producing pituitary adenoma is a new type of Cushing's syndrome. (+info)
Evaluation and management of adrenal masses.
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BACKGROUND: The widespread use of abdominal imaging has led to increased detection of adrenal tumors. The significance of these masses, as well as the optimal management approach to treatment, has generated some controversy regarding further evaluation and therapy. METHODS: The authors reviewed the literature regarding the evaluation and management of these masses, particularly adrenal incidentalomas. Based on their institutional experience, they propose a diagnostic, evaluation, and management algorithm for treating adrenal masses. RESULTS: Appearance and clinical history should indicate how to perform the biochemical evaluation, keeping in mind that the presence of pheochromocytomas must be ruled out. Radiological evaluation by CT or MRI provides useful parameters to identify malignant lesions. Surgery is indicated for masses that are larger than 5 cm in diameter or suspected of malignancy. Fine-needle aspiration biopsy should be used when other extra-adrenal malignancies are suspected and after pheochromocytoma has been ruled out. CONCLUSIONS: Careful analysis of each adrenal mass is essential to effectively avoid potential problems. Guidelines to manage patients with adrenal masses are needed. (+info)
Effects of the implementation of an 84-hour workweek on neurobehavioral test performance and cortisol responsiveness during testing.
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OBJECTIVES: This study examined whether long workhours in combination with an extended workweek (12 hours/7 days), as requested by the workers, impaired attention and cognitive performance and whether the degree of hypothalamic-pituitary-adrenal (HPA) activation was related to the response to the performance tasks. METHODS: A group of 41 male construction workers between 21 and 60 (mean 39) years of age who worked 84 hours a week, with alternate weeks off, was compared with a group of 23 male construction workers between 24 and 65 (mean 43) years of age who had a traditional 40-hour work schedule. Neurobehavioral test performance, self-ratings of fatigue and sleepiness, and salivary cortisol levels were evaluated in a counterbalanced repeated-measures design. RESULTS: The 84-hour group did not show any signs of reduced test performance or elevated fatigue and sleepiness. The 84-hour group had faster reaction times on day 7 than on days 1 and 5. Although the expected activation of the HPA axis was only found in the total study sample when workdays 1 and 5 were collapsed, the HPA activation can be considered normal. CONCLUSIONS: The results suggest that an 84-hour work regimen in response to requests from workers does not induce more performance deficits than an ordinary 40-hour workweek. An extended work schedule of 84 hours cannot in the short-term be considered to affect basic mental capabilities negatively. (+info)