scholarly journals A high-sensitivity test in the assessment of adrenocortical insufficiency: 10 microg vs 250 microg cosyntropin dose assessment of adrenocortical insufficiency

1998 ◽  
Vol 159 (2) ◽  
pp. 275-280 ◽  
Author(s):  
JG Gonzalez-Gonzalez ◽  
NE De la Garza-Hernandez ◽  
LG Mancillas-Adame ◽  
J Montes-Villarreal ◽  
JZ Villarreal-Perez
Keyword(s):  
Healthy Subjects ◽  
Low Dose ◽  
Standard Dose ◽  
Addison’S Disease ◽  
High Sensitivity ◽  
Serum Cortisol ◽  
Dose Assessment ◽  
Addison's Disease ◽  
Acth Test ◽  
Adrenocortical Insufficiency

The short cosyntropin (synthetic ACTH) test is recognized as the best screening manoeuvre in the assessment of adrenocortical insufficiency. Recent data, however, suggest that i.v. administration of 250 microg cosyntropin could be a pharmacological rather than a physiological stimulus, losing sensitivity for detecting adrenocortical failure. Our objective was to compare 10 vs 250 microg cosyntropin in order to find differences in serum cortisol peaks in healthy individuals, the adrenocortical response in a variety of hypothalamic-pituitary-adrenal axis disorders and the highest sensitivity and specificity serum cortisol cut-off point values. The subjects were 83 healthy people and 37 patients, the latter having Addison's disease (11), pituitary adenomas (7), Sheehan's syndrome (9) and recent use of glucocorticoid therapy (10). Forty-six healthy subjects and all patients underwent low- and standard-dose cosyntropin testing. In addition, 37 controls underwent the low-dose test. On comparing low- and standard-dose cosyntropin testing in healthy subjects there were no statistical differences in baseline and peaks of serum cortisol. In the group of patients, 2 out of 11 cases of Addison's disease showed normal cortisol criterion values during the standard test but abnormal during the low-dose test. In our group of patients and controls, the statistical analysis displayed a better sensitivity of the low-dose vs standard-dose ACTH test at 30 and 60 min. In conclusion, these results suggest that the use of 10 microg rather than 250 microg cosyntropin i.v. in the assessment of suspicious adrenocortical dysfunction gives better results.

Low dose (1 μg) ACTH test in the evaluation of adrenal dysfunction in pre-clinical Addison's disease

2000 ◽  
Vol 53 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Stefano Laureti ◽  
Emanuela Arvat ◽  
Paola Candeloro ◽  
Lidia Di Vito ◽  
Ezio Ghigo ◽  
...  
Keyword(s):  
Low Dose ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Acth Test

Reproducibility of the cortisol response to stimulation with a low dose of ACTH(1–24): the effect of basal cortisol levels and comparison of low-dose with high-dose secretory dynamics

1993 ◽  
Vol 136 (1) ◽  
pp. 167-172 ◽  
Author(s):  
S. Crowley ◽  
P. C. Hindmarsh ◽  
J. W. Honour ◽  
C. G. D. Brook
Keyword(s):  
Cortisol Level ◽  
Low Dose ◽  
Standard Dose ◽  
Serum Cortisol ◽  
Cortisol Concentration ◽  
Acth Stimulation ◽  
Basal Cortisol ◽  
Basal Cortisol Level ◽  
Adrenal Response ◽  
Serum Cortisol Concentration

ABSTRACT We compared the reproducibility and repeatability of the acute adrenal response to low doses (90 and 500 ng/1·73 m2) of Synacthen (ACTH(1–24)) with that of the standard dose (250 μg/1·73 m2). We also examined the effect of basal cortisol levels on peak values achieved after stimulation with a low dose. ACTH(1–24) was given to six male volunteers: 90 ng/1·73 m2 twice at 90-min intervals on day 1, and 90 and 500 ng/1·73 m2 once on day 2 and 250 μg/1·73 m2 once on day 3. The rise in serum cortisol concentration with repeated low doses of ACTH was not attenuated (161 ± 49 (s.d.) nmol/l on initial vs 150 ± 41 nmol/l on repeat stimulation; P = 0·5) and this was reproducible (161 ± 49 nmol/l on day 1 vs 148 ± 15 nmol/l on day 2; P = 0·6). A dose of 500 ng ACTH(1–24)/1·73 m2 produced a maximal adrenal response in that the rise in serum cortisol concentration at 20 min was identical with that produced at the same time by the standard dose of 250 μg/1·73 m2. There was a strong positive correlation between the basal cortisol level and peak cortisol concentration after low-dose ACTH stimulation (r = 0·93, P < 0·001) but not between the basal cortisol level and the incremental rise (r= −0·1, P = 0·69). These results suggest that the cortisol response to low-dose ACTH stimulation is reproducible and not attenuated by repeat stimulation at 90-min intervals. The incremental rise in serum cortisol concentration after ACTH stimulation appears constant in these situations and is not influenced by the basal cortisol level. When there is concern that the standard dose may be excessive and mask subtle but important changes in adrenal function, the low dose (500 ng) of ACTH should be used. Journal of Endocrinology (1993) 136, 167–172

scholarly journals Microsatellite Polymorphism of the MHC Class I Chain-Related (MIC-A and MIC-B) Genes Marks the Risk for Autoimmune Addison’s Disease

1999 ◽  
Vol 84 (10) ◽  
pp. 3701-3707 ◽  
Author(s):  
Giovanni Gambelunghe ◽  
Alberto Falorni ◽  
Mehran Ghaderi ◽  
Stefano Laureti ◽  
Cristina Tortoioli ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Absolute Risk ◽  
Central Italy ◽  
Addison’S Disease ◽  
Class I ◽  
Addison's Disease ◽  
Specific Marker ◽  
Hla Dr ◽  
Intron 1 ◽  
Hla Dr3

Abstract The major histocompatibility complex class I chain-related MIC-A and MIC-B genes are located on chromosome 6 between the histocompatibility leucocyte antigen (HLA)-B and the B-associated transcript genes. The presence of 21-hydroxylase autoantibodies is a sensitive and specific marker of autoimmune Addison’s disease. We studied the polymorphism of exon 5 of the MIC-A gene, of intron 1 of the MIC-B gene, and of HLA-DRB1, -DQA1, and -DQB1 genes in 28 autoimmune (21-hydroxylase autoantibody positive) Addison’s disease patients and in 75 healthy subjects from central Italy. The MIC-A5.1 allele was significantly more frequent in Addison’s disease patients (79%) than in healthy subjects (36%) [odds ratio (OR) = 6.52, corrected P (Pc) = 0.0015], whereas MIC-A6 was significantly reduced in affected subjects (15% vs. 56%, OR = 0.13, Pc = 0.002). The A5.1/A5.1 genotype had an OR for autoimmune Addison’s disease as high as 18.0 and an absolute risk of 1 per 1131. In the presence of MIC-A5.1, MICB-CA-25 was significantly increased in Addison’s disease patients (25% vs. 4%, OR = 8.0, P = 0.0039, Pc = 0.047). The MICB-CA-17 allele was absent in Addison’s disease patients, but present in more than 25% healthy individuals (OR = 0.10, P = 0.0025, Pc = 0.03). Among HLA-DR and -DQ haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3/DQ2) was significantly more frequent in Addison’s disease patients than in healthy subjects, but only in the presence of MIC-A5.1. The frequency of MIC-A5.1 was significantly increased in Addison’s disease patients only in the presence of HLA-DR3-DQ2. Our study demonstrates that susceptibility to autoimmune Addison’s disease is linked to the MIC-A microsatellite allele 5.1 and that both MIC-A5.1 and HLA-DR3/DQ2 are necessary to confer increased genetic risk for Addison’s disease.

scholarly journals A Case of Addison's Disease Confirmed with Low Dose Cosyntropin Stimulation Test

2007 ◽  
Vol 54 (5) ◽  
pp. 765-769 ◽  
Author(s):  
Kenji OKI ◽  
Kiminori YAMANE ◽  
Masayasu YONEDA ◽  
Hideki NOJIMA ◽  
Hiroshi WATANABE ◽  
...  
Keyword(s):  
Low Dose ◽  
Addison’S Disease ◽  
Stimulation Test ◽  
Addison's Disease ◽  
Cosyntropin Stimulation Test

Mineralocorticoid Before Glucocorticoid Deficiency in a Dog with Primary Hypoadrenocorticism and Hypothyroidism

2013 ◽  
Vol 49 (1) ◽  
pp. 54-57 ◽  
Author(s):  
Kathryn M. McGonigle ◽  
John F. Randolph ◽  
Sharon A. Center ◽  
Richard E. Goldstein
Keyword(s):  
Clinical Signs ◽  
Addison’S Disease ◽  
Serum Cortisol ◽  
Primary Hypothyroidism ◽  
Addison's Disease ◽  
Acth Stimulation Test ◽  
Acth Stimulation ◽  
Clinical Illness ◽  
Glucocorticoid Deficiency ◽  
Electrolyte Abnormalities

A dog with an unexpected presentation of primary hypoadrenocorticism was evaluated for clinical signs and electrolyte abnormalities characteristic of Addison’s disease. Although the initial adrenocorticotropic hormone (ACTH) stimulation test documented serum cortisol concentrations within the reference range, subsequent assessments confirmed hypoaldosteronism. Mineralocorticoid replacement promptly normalized electrolytes and transiently improved clinical illness. Six weeks after initial ACTH stimulation testing, the dog became glucocorticoid deficient. Concurrent primary hypothyroidism was also documented. Hypoaldosteronism preceding hypocortisolemia is a unique presentation of canine Addison’s disease.

scholarly journals Gene Expression to Guide Glucocorticoid Replacement in Autoimmune Addison’s Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A83-A83
Author(s):  
Åse Bjorvatn Sævik ◽  
Anette Wolff ◽  
Sigridur Björnsdottir ◽  
Katerina Simunkova ◽  
Martha S Hynne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Addison’S Disease ◽  
Serum Cortisol ◽  
Normal Serum ◽  
Addison's Disease ◽  
Expression Levels ◽  
Morning Cortisol ◽  
Cortisol Levels ◽  
Compare Gene Expression ◽  
Gene Expression Levels

Abstract Objective: Deciding the optimal doses of glucocorticoid (GC) replacement treatment in autoimmune Addison’s disease (AAD) is impeded by the lack of reliable biomarkers. This frequently results in over-treatment, with alarming and persistent side-effects, or under-replacement, which could be fatal. There is a need to think new in the quest for robust biomarkers to optimize GC replacement in AAD at an individual level. Aim: We aimed to identify genes that are consistently up- or down-regulated in patients with AAD in response to different GC replacement doses. This information can be used to establish novel biomarkers to guide GC treatment in AAD. Methods: Step 1: Global microarray expression analysis on RNA from whole blood before and after intravenous infusion of 100 mg hydrocortisone (HC) in 10 patients with AAD. To verify the results, we performed real-time PCR to compare gene expression levels of three of the highly differentially expressed genes (FKBP5, MMP9, and DSIPI) to compare gene expression levels before and two, four, and six hours after the HC infusion. Step 2: Rt-PCR to compare expression levels of 93 GC-regulated genes in normal versus very low morning cortisol levels in 27 patients with AAD. Results: Step 1: Two hours after infusion of 100 mg HC, there was a marked increase in FKBP5, MMP9, and DSIPI expression levels. MMP9 and DSIPI expression levels correlated with serum cortisol. Step 2: Expression levels of CEBPB, DDIT4, FKBP5, DSIPI, and VDR were increased and ADARB1, ARIDB5, and POU2F1 decreased in normal versus very low morning cortisol. Normal serum cortisol levels positively correlated with DSIPI, DDIT4, and FKBP5 expression. Conclusions: We introduce gene expression as a novel approach to guide GC replacement in AAD. We suggest that gene expression of DSIPI, DDIT4, and FKBP5 are particularly promising candidate biomarkers of GC replacement, followed by MMP9, CEBPB, VDR, ADARB1, ARID5B, and POU2F1.

scholarly journals Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison’s Disease

2021 ◽  
Author(s):  
Åse Bjorvatn Sævik ◽  
Anette B Wolff ◽  
Sigridur Björnsdottir ◽  
Katerina Simunkova ◽  
Martha Schei Hynne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Addison’S Disease ◽  
Serum Cortisol ◽  
Normal Serum ◽  
Addison's Disease ◽  
Rt Pcr ◽  
Expression Levels ◽  
Morning Cortisol ◽  
Cortisol Levels ◽  
Transcriptional Biomarkers

Abstract Background No reliable biomarkers exist to guide glucocorticoid (GC) replacement treatment in autoimmune Addison’s disease (AAD), leading to overtreatment with alarming and persistent side-effects or undertreatment, which could be fatal. Objective To explore changes in gene expression following different GC replacement doses as a means of identifying candidate transcriptional biomarkers to guide GC replacement in AAD. Methods Step 1: Global microarray expression analysis on RNA from whole blood before and after intravenous infusion of 100 mg hydrocortisone (HC) in 10 patients with AAD. In three of the most highly upregulated genes, we performed real-time PCR (rt-PCR) to compare gene expression levels before and two, four, and six hours after the HC infusion. Step 2: Rt-PCR to compare expression levels of 93 GC-regulated genes in normal versus very low morning cortisol levels in 27 patients with AAD. Results Step 1: Two hours after infusion of 100 mg HC, there was a marked increase in FKBP5, MMP9, and DSIPI expression levels. MMP9 and DSIPI expression levels correlated with serum cortisol. Step 2: Expression levels of CEBPB, DDIT4, FKBP5, DSIPI, and VDR were increased and ADARB1, ARIDB5, and POU2F1 decreased in normal versus very low morning cortisol. Normal serum cortisol levels positively correlated with DSIPI, DDIT4, and FKBP5 expression. Conclusions We introduce gene expression as a novel approach to guide GC replacement in AAD. We suggest that gene expression of DSIPI, DDIT4, and FKBP5 are particularly promising candidate biomarkers of GC replacement, followed by MMP9, CEBPB, VDR, ADARB1, ARID5B, and POU2F1.

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