A Very Low Dose Intravenous Dexamethasone Suppression Test as an Index of Glucocorticoid Sensitivity

Faria, Cláudia Dutra Costantin; Cobra, Jayme Fogagnolo; Silva, Tatiane Sousa e; Melo, Murilo Rezende; Rocha, Mylene Neves; Hayashi, Lílian Sukusima; Faria, Thelma Gomes; Almeida, Julio Antonio de Souza e; Kater, Cláudio E.; Longui, Carlos Alberto

doi:10.1159/000117392

Cited by 10 publications

(17 citation statements)

References 33 publications

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“…Significant reduction of ACTH and cortisol concentrations occurred after VLD-IV-DST, indicating that this test was effective in establishing a spectrum of sensitivity to GC in vivo as previously demonstrated (Faria et al, 2008;Cobra et al, 2009;Cavalcante et al, 2010). However, the extent of suppression was lower in patients than in controls (23.48 vs 53.2%, respectively), indicating lower GC sensitivity in SLE patients during the remission phase of the disease.…”

Section: Discussionsupporting

confidence: 58%

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Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

Melo¹,

Melo²,

Saramago³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Glucocorticoids (GCs) are key drugs in the treatment of systemic lupus erythematosus (SLE). GC dose reduction during remission is related to disease activity, GC dose used, length of treatment, and individual GC sensitivity. We compared GC receptor α (GRα) isoform and nuclear factor kappaB (NF-κB) messenger RNA quantitation and in vivo GC sensitivity between SLE patients during remission and healthy controls. We performed a cross-sectional study of 19 women aged 22-49 years, including 9 SLE patients in clinical remission taking ≤5 mg prednisone and 10 matched controls. We evaluated GC sensitivity using 2 cortisol suppression tests: a very-low-dose intravenous dexamethasone suppression test (VLD-IV-DST) and a low-dose oral dexamethasone suppression test. GRα and NF-κB mRNA were quantified using real-time polymerase chain reaction. Although basal cortisol and adrenocorticotropic hormone levels were similar between the groups, the percentage of cortisol reduction after the VLD-IV-DST was 56% lower in SLE patients than in controls (P = 0.014). GRα and NF-κB gene expression levels were similar between the groups. The low-dose oral dexamethasone test caused intense cortisol suppression in all individuals, limiting the ability of this test to discriminate individual GC sensitivity. A positive correlation was found between the extent of cortisol suppression in vivo (VLD-IV-DST) and the number of days elapsed since the last flare of lupus activity. Despite clinical remission, SLE patients displayed partial GC resistance recognized by the VLD-IV-DST. The mechanism of this resistance is unrelated to altered GRα and NF-κB mRNA expression.

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Section: Discussionsupporting

confidence: 58%

“…We recently described the use of this test for the recognition of individual GC sensitivity in various age groups (Faria et al, 2008). Briefly, after a fasting period of 10-12 h and 30 min of rest, a blood sample was obtained for cortisol and adrenocorticotropic hormone (ACTH) measurements.…”

Section: Vld-iv-dst and Low-dose Oral Dexamethasone Suppression Testmentioning

confidence: 99%

Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

Melo¹,

Melo²,

Saramago³

et al. 2013

Genet. Mol. Res.

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“…Our group already described the influence of age (Faria et al, 2008) and obesity on glucocorticoid sensitivity and GRα quantitation.…”

Section: Discussionmentioning

confidence: 99%

“…We recently described how this new test can be used to evaluate individual glucocorticoid sensitivity in different age groups (Faria et al, 2008). Briefly, after a fasting period of 10-12 h and 30 min of resting, a blood sample was taken for cortisol measurement (and also for separation of peripheral mononuclear cells).…”

Section: Very Low Dose Intravenous Dexamethasone Suppression Test (Vlmentioning

confidence: 99%

Quantitation of glucocorticoid receptor alpha and NF-κB pathway mRNA and its correlation with disease activity in rheumatoid arthritis patients

Cavalcante

Melo²,

Dinis³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. We measured NF-κB, IKK, c-Fos, and GRα mRNA expression and in vivo glucocorticoid sensitivity in patients with rheumatoid arthritis. A very low dose intravenous dexamethasone suppression test and real-time PCR quantitation of mRNA of these genes were performed on blood samples from 21 rheumatoid arthritis patients who were not on glucocorticoids during the previous four months and on blood samples from 20 healthy individuals. Mean rheumatoid arthritis duration was 8.8 years, and mean disease activity, as assessed by Disease Activity Score 28 (DAS28), was 4.45. Basal cortisol and the percentage of cortisol reduction after the very low dose intravenous dexamethasone suppression test, as well as NF-κB, IKK, c-Fos, and GRα mRNA expression, were similar among groups. We did not observe significant correlations between glucocorticoid in vivo sensitivity and DAS28. There was a positive correlation between 2301 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 9 (4): 2300-2310 (2010) Gene expression in rheumatoid arthritis DAS28 and NF-κB, IKK, and GRα, but not c-Fos. In the multivariate analysis, only NF-κB mRNA remained as an independent variable for predicting DAS28.

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“…In order to exclude the interference on dexamethasone metabolism during the first passage through the liver [31], we subsequently described the use of i.v. bolus administration of dexamethasone in a dose of 20 µg/m 2 [32]. This very low dose of i.v.…”

Section: In Vivo Evaluation Of Gc Sensitivitymentioning

confidence: 99%

Evaluation of Glucocorticoid Sensitivity and Its Potential Clinical Applicability

Longui

Faria

2009

Horm Res Paediatr

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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.

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A Very Low Dose Intravenous Dexamethasone Suppression Test as an Index of Glucocorticoid Sensitivity

Cited by 10 publications

References 33 publications

Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

Persistent glucocorticoid resistance in systemic lupus erythematosus patients during clinical remission

Quantitation of glucocorticoid receptor alpha and NF-κB pathway mRNA and its correlation with disease activity in rheumatoid arthritis patients

Evaluation of Glucocorticoid Sensitivity and Its Potential Clinical Applicability

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