Acute Effect of Increasing Glucocorticoid Replacement Dose on Cardiovascular Risk and Insulin Sensitivity in Patients With Adrenocorticotrophin Deficiency

Petersons, Carolyn J.; Mangelsdorf, Brenda L.; Thompson, Campbell; Burt, Morton G.

doi:10.1210/jc.2013-4305

Cited by 40 publications

(47 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The consequences of temporary hypercortisolism following therapy with HC are unknown so far [5] but have been described to be associated with deleterious effects on body composition. In fact, higher glucocorticoid replacement doses may have adverse effects on both body fat and lipid profile [3] as well as on endothelial function [7]. However, our findings did not support this effect, which has been thought to be associated with increased overall mortality, at least in patients with non-functioning pituitary adenoma and hormonal insufficiency [9].…”

contrasting

confidence: 70%

“…Adenomas are the most common disease affecting the pituitary with an estimated prevalence of 16.7% [4]. Compared to a normal population, patients with hypopituitarism are at greater risk to develop cardiovascular and cerebrovascular disease, conditions associated with higher mortality [1,7]. Increased cardiovascular mortality in hypopituitarism may be the direct effect of inadequate availability and action of pituitary hormones.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cardiovascular risk factors and disease in patients with hypothalamic-pituitary disorders

Harbeck

Haas

Suefke

et al. 2015

International Journal of Cardiology

View full text Add to dashboard Cite

contrasting

confidence: 70%

mentioning

confidence: 99%

Cardiovascular risk factors and disease in patients with hypothalamic-pituitary disorders

Harbeck

Haas

Suefke

et al. 2015

International Journal of Cardiology

View full text Add to dashboard Cite

“…ACTH deficiency leads to hypocortisolism during acute illness,27 with a significant risk of life‐threatening adrenal crisis. It is also intimately associated with the adverse metabolic effects of chronic supraphysiological glucocorticoid replacement 18, 28. We have shown that mortality risk is increased almost fourfold in patients taking total daily hydrocortisone doses of 30 mg or higher.…”

Section: Discussionmentioning

confidence: 99%

ACTH and gonadotropin deficiencies predict mortality in patients treated for nonfunctioning pituitary adenoma: long‐term follow‐up of 519 patients in two large European centres

O’Reilly

Reulen

Gupta

et al. 2016

Clinical Endocrinology

View full text Add to dashboard Cite

SummaryContext and ObjectiveNonfunctioning pituitary adenomas (NFPAs) are the most common subtype of pituitary tumour. Hypopituitarism is observed in NFPAs due to tumour‐ or treatment‐related factors and may increase mortality risk. Here, we analysed the associations of hypopituitarism, hormone replacement and mortality in a large NFPA cohort derived from two large European centres.Design, Setting and ParticipantsCase note review of all patients treated for NFPA in University Hospitals Birmingham and Beaumont Hospital Dublin between 1999 and 2014 was performed.Main Outcome MeasuresClinical presentation, treatment strategies, pituitary function and vitality status were recorded in each patient. A multivariate Cox regression model was used to examine the association between hypopituitarism, hormone replacement and premature mortality.ResultsA total of 519 patients were included in the analysis. Median duration of follow‐up was 7·0 years (0·5–43). A total of 81 deaths were recorded (15·6%). On multivariate analysis, adrenocorticotropic hormone (ACTH) and gonadotropin (Gn) deficiencies were associated with an increased relative risk of death (OR 2·26, 95% CI 1·15–4·47, P = 0·01 and OR 2·56, 95% CI 1·10–5·96, P = 0·01, respectively). Increased hydrocortisone (HC) (P‐trend = 0·02) and lower levothyroxine (LT4) doses (P‐trend = 0·03) were associated with increased risk of death. Mortality increased with the degree of pituitary failure observed (P‐trend = 0·04).ConclusionACTH and gonadotropin‐deficient patients have higher mortality rates compared to those with intact hormonal axes. Excessive HC and suboptimal LT4 replacement may also increase risk of death. Complex associations between hormone deficiency and replacement underpin the increased mortality risk in NFPA patients.

show abstract

“…We have undertaken a series of linked clinical studies to assess if plasma TSP1 and/or TSP1 mRNA expression in PBMC in healthy volunteers are acutely upregulated by dexamethasone; if plasma TSP1 is elevated in patients with Cushing's syndrome; and if plasma TSP1 in patients with secondary adrenal insufficiency is adequately sensitive to detect a small change in the hydrocortisone dose. Patients with secondary adrenal insufficiency " Plasma was available from 16 of 17 patients with secondary adrenal insufficiency (eight male and eight female, median age 56 years, range 22-87), who participated in a study investigating the effects of an increase in the hydrocortisone dose on cardiovascular risk markers and insulin sensitivity (24). Samples were collected fasting w2 h after the morning hydrocortisone dose when on a standard dose of %20 mg/day (median 16 mg/day, range 10-20 mg) and 1 week after hydrocortisone was increased to 30 mg/day.…”

Section: Introductionmentioning

confidence: 99%

Thrombospondin-1 is a glucocorticoid responsive protein in humans

Barclay

Petersons

Keshvari

et al. 2016

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Thrombospondin-1 (TSP1) is a matricellular protein whose gene expression has previously been shown to increase acutely after exposure to dexamethasone in vitro. The aim of this study was to determine if TSP1 is altered by acute and chronic states of glucocorticoid excess in human subjects. Design and methods: Three studies have been undertaken to assess the difference or change in TSP1 in response to altered glucocorticoid activity: i) an acute interventional study assessed the effects of a single 4 mg dose of dexamethasone in 20 healthy volunteers; ii) a cross-sectional study compared plasma TSP1 in 20 healthy volunteers and eight patients with Cushing's syndrome; iii) an interventional study assessed the effect on plasma TSP1 of an increase in hydrocortisone dose from %20 mg/day to 30 mg/day for 7 days in 16 patients with secondary adrenal insufficiency. Results: In healthy volunteers, 4 mg dexamethasone significantly increased peripheral blood mononuclear cell (PBMC) TSP1 mRNA levels (P!0.0001) and plasma TSP1 concentrations (P!0.0001), peaking at 12 h. Median (interquartile range) plasma TSP1 was higher in Cushing's, 638 (535-756) ng/ml, than in healthy volunteers, 272 (237-336) ng/ml (P!0.0001). Plasma TSP1 O400 ng/ml diagnosed Cushing's syndrome with sensitivity of 100% and specificity of 85%. The higher hydrocortisone dose increased plasma TSP1 from 139 (86-199) to 256 (133-516) ng/ml, (P!0.01) in patients with secondary adrenal insufficiency. Conclusions: TSP1 is a glucocorticoid responsive protein in humans. Further research is required to determine if plasma TSP1 has a role as a glucocorticoid biomarker.

show abstract

Acute Effect of Increasing Glucocorticoid Replacement Dose on Cardiovascular Risk and Insulin Sensitivity in Patients With Adrenocorticotrophin Deficiency

Cited by 40 publications

References 38 publications

Cardiovascular risk factors and disease in patients with hypothalamic-pituitary disorders

Cardiovascular risk factors and disease in patients with hypothalamic-pituitary disorders

ACTH and gonadotropin deficiencies predict mortality in patients treated for nonfunctioning pituitary adenoma: long‐term follow‐up of 519 patients in two large European centres

Thrombospondin-1 is a glucocorticoid responsive protein in humans

Contact Info

Product

Resources

About