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M Duclos, JB Corcuff, F Pehourcq, and A Tabarin

OBJECTIVE: Muscular exercise induces hypothalamo-pituitary-adrenal (HPA) axis activation and when regularly repeated, as in endurance training, leads to HPA axis adaptation. To assess whether non-professional endurance-trained (ET) men with a substantial training load and no clinical or biological features of HPA axis overactivity can present subtle alterations of HPA axis sensitivity to glucocorticoid negative feedback, nine ET men were subjected to HPA axis testing using the dexamethasone-corticotrophin-releasing hormone (CRH) test. DESIGN: Nine endurance-trained men and eight healthy age-matched sedentary men were studied. Morning plasma cortisol and 24 h urinary free cortisol (UFC) were determined and a low dose dexamethasone suppression test (LDDST) was performed followed by CRH stimulation (dexamethasone-CRH test). RESULTS: After a day without physical exercise, at 0800 h, plasma ACTH and cortisol concentrations, and the 24 h UFC and UFC/urinary creatinine (UC) ratio were similar in ET and sedentary men. By contrast, clear differences between the groups were seen in cortisol and ACTH responses to the dexamethasone-CRH test. In eight ET subjects, after LDDST, basal ACTH and cortisol levels were similar to those of sedentary men, whereas one ET subject displayed a poor suppression of cortisol level (131 nmol/l). After injection of CRH, however, three of nine ET men's cortisol levels were not suppressed by dexamethasone but instead displayed significant CRH-induced increase (peak cortisol: 88, 125 and 362 nmol/l). No sedentary subject exhibited any increase in cortisol levels. CONCLUSION: Three of nine ET men with a mean maximum rate of O2 uptake (VO2, max) of 61 ml/kg per min, running 50-70 km per week, were resistant to glucocorticoid suppression during the combined dexamethasone-CRH test.

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A Tabarin, JB Corcuff, M Rashedi, A Navarranne, D Ducassou, and P Roger

Recent reports suggest that, contrary to radioimmunoassays (RIA), immunoradiometric assays (IRMA) artifactually decrease plasma ACTH levels in patients with the ectopic ACTH syndrome. Discrepancies between RIA and IRMA results may provide a means of discriminating this entity from Cushing's disease. We have compared the results of these two techniques, together with those of a β-endorphin assay, in 1 7 patients with Cushing's disease, 9 with the ectopic ACTH syndrome and 30 controls. ACTH-RIA and ACTH-IRMA levels in patients with Cushing's disease were similar (17.5±2.5 vs 15.1±2.8 pmol/l) and were correlated (rs=0.59, p<0.01). ACTH-RIA levels in patients with the ectopic ACTH syndrome were higher than ACTH-IRMA levels (27.3±2.9 vs 14.5±2.5, p<0.01) and these did not correlate. The ACTH-RIA and ACTH-RIA/ACTH-IRMA ratio levels in patients with the ectopic ACTH syndrome were higher than those of patients with Cushing's disease (p<0.01), but they overlapped with these in 27 and 31% of cases respectively. Plasma β-endorphin level was higher in patients with the ectopic ACTH syndrome than in patients with Cushing's disease (81.9±19.4 vs 26.4±5.6 pmol/l, p <0.01) and was correlated with ACTH only in patients with Cushing's disease. The overlap in β-endorphin and β-endorphin/ACTH-IRMA molar ratio levels between the two groups were 19 and 27% respectively. Although no parameter could be used to make clearcut distinction between Cushing's disease and the ectopic ACTH syndrome, the discriminative power of β-endorphin level was clearly better than that of the comparison between ACTH-RIA and ACTH-IRMA levels.

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A. Tabarin, F. San Galli, S. Dezou, F. Leprat, J.-B. Corcuff, J.-L. Latapie, J. Guerin, and P. Roger

Abstract.

The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.