cosyntropin and Cardiovascular-Diseases

Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood.. Cross-sectional study.. We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH.. Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively).. We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.

Topics: Addison Disease; Biomarkers; Cardiovascular Diseases; Cosyntropin; Cross-Sectional Studies; Extracellular Matrix Proteins; Female; Glucocorticoids; Humans; Inflammation; Leptin; Male; Neoplasm Proteins; Quality of Life

Recent studies in critically ill populations have suggested both adrenal insufficiency (AI) and vitamin D deficiency to be associated with worse clinical outcome. There are multiple mechanisms through which these pleiotropic hormones might synergistically influence critical illness.. The aim of the study was to investigate potential relationships between vitamin D status, adrenal status, and cardiovascular dysfunction in critically ill children.. We conducted a secondary analysis of data from a prospective cohort study.. The study was conducted on 319 children admitted to 6 Canadian tertiary-care pediatric intensive care units.. Vitamin D status was determined through total 25-hydroxyvitamin D (25OHD) levels. AI was defined as a cortisol increment under 9 μg/dL after low-dose cosyntropin. Clinically significant cardiovascular dysfunction was defined as catecholamine requirement during pediatric intensive care unit admission.. Using 3 different thresholds to define vitamin D deficiency, no association was found between vitamin D status and AI. Furthermore, linear regression failed to identify a relationship between 25OHD and baseline or post-cosyntropin cortisol. However, the association between AI and cardiovascular dysfunction was influenced by vitamin D status; compared to children with 25OHD above 30 nmol/L, AI in the vitamin D-deficient group was associated with significantly higher odds of catecholamine use (odds ratio, 5.29 vs 1.63; P = .046).. We did not find evidence of a direct association between vitamin D status and critical illness-related AI. However, our results do suggest that vitamin D deficiency exacerbates the effect of AI on cardiovascular stability in critically ill children.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adrenal Cortex; Adrenal Insufficiency; Calcifediol; Canada; Cardiovascular Diseases; Cardiovascular System; Catecholamines; Child; Child, Preschool; Cohort Studies; Cosyntropin; Hormones; Humans; Hydrocortisone; Infant; Intensive Care Units, Pediatric; Nutritional Status; Prospective Studies; Tertiary Care Centers; Vitamin D Deficiency