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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]

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 μg/m2 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 μg/m2 of DEX is useful to evaluate individual sensitivity to GC in different age groups. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]