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Background/aims: The wide variability of responses to corticotherapy suggests a role for individual recognition of steroid sensitivity in order to customize treatment. Oral dexamethasone (DEX) administration may be hindered by the rate of its intestinal absorption and the liver first-passage effect. In this study we suggest that an intravenous very low dose DEX suppression test (VLD IV-DST) can be used as an index for glucocorticoid (GC) sensitivity., Methods: We evaluated 87 normal subjects: 44 prepubertal children, 23 adolescents and 20 adults with a VLD IV-DST using 20 mug/m(2) of DEX (dose able to recognize GC sensitivity). Cortisol was initially measured at several time-points after DEX prompting us to establish its nadir and subsequent simplification of the test by measuring cortisol at baseline and after 120 min., Results: Baseline cortisol was similar in adolescents and in adults, but lower in children. There was a spectrum of individual responses in all age groups. The percent reduction of cortisol after 120 min was different in these three age groups, with median values of 44.4% in children, 25.9% in adolescents and 61.6% in adults., Conclusion: This simplified VLD IV-DST using 20 mug/m(2) of DEX is useful to evaluate individual sensitivity to GC in different age groups., ((c) 2008 S. Karger AG, Basel)

Background/Aim: Healthy individuals present variable responses of the hypothalamic-pituitary-adrenal (HPA) axis induced by different patterns of physical training. The aim of this study was to evaluate whether prolonged low-grade physical training influences the HPA axis and also glucocorticoid receptor-α (GRα) mRNA levels in mononuclear cells of obese adolescents. Methods: We studied 19 patients with BMI above the 95th percentile (male:female ratio 7:12) aged from 9.5 to 15.5 years. Patients underwent a 12-week physical exercise program. Before and after exercise, in vivo glucocorticoid sensitivity was determined by employing a very-low-dose intravenous dexamethasone suppression test, and in vitro GRα mRNA levels were evaluated by quantitative real-time PCR. Results: After exercise there was a trend to reduce the in vivo glucocorticoid sensitivity (p = 0.071) and a significant increase in GRα mRNA levels (p = 0.025). Conclusion: For this subset of obese adolescents, prolonged low-grade physical training tended to reduce glucocorticoid sensitivity. The discrepancy of cortisol response to dexamethasone and the GRα mRNA measurement suggest a post-receptor phenomenon or should be related to target tissue-specific differences in glucocorticoid sensitivity. Future studies should address the adaptive GRα mRNA during different exercise protocols, and also the correlation of pituitary sensitivity with glucocorticoid target tissue sensitivity. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GC) play an important role in physiologic and pathophysiologic adaptive responses to stress. The majority of these effects are mediated by the GC receptors (GR). GC sensitivity largely depends of the amount of available GR, and their ability to bind the GC-responsive element and/or other nuclear transcription factors, leading to modulation of the expression of GC target genes. Clinical conditions of tissue-specific GC resistance or GC hypersensitivity have been described in several diseases, such as chronic inflammatory and autoimmune conditions, and in visceral obesity, such as metabolic syndrome. Several in vivo and in vitro methods have been described, allowing the evaluation and quantitation of GC sensitivity. The recognition of these parameters has improved our comprehension of the mechanisms involved in those diseases, with potential implications for the diagnosis and therapy of such abnormalities. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]