Glucocorticoid Replacement and Mortality in Patients with Nonfunctioning Pituitary Adenoma

Zueger, Thomas; Kirchner, Paul; Herren, C; Fischli, Stefan; Zwahlen, Marcel; Christ, Emanuel; Stettler, Christoph

doi:10.1210/jc.2012-2432

Cited by 84 publications

(66 citation statements)

References 11 publications

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“…We have shown that mortality risk is increased almost fourfold in patients taking total daily hydrocortisone doses of 30 mg or higher. Zueger et al 18. also found increased mortality with higher hydrocortisone dosages in ACTH‐deficient NFPA patients in a Swiss study; this finding was consistent for both total and weight‐adjusted hydrocortisone doses, and the same associations have been observed in acromegaly 11.…”

Section: Discussionsupporting

confidence: 56%

“…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: 97%

“…However, an independent association between RT and mortality in NFPA has not been consistently replicated across studies, and both the Tomlinson study and the Dutch study of van Varsseveld found no increase in mortality between irradiated and nonirradiated patients 16, 17. Further confounders in this area include treatment‐associated effects on mortality; overzealous hydrocortisone (HC) replacement in patients with adrenocorticotropic hormone (ACTH) deficiency has been associated with increased mortality, both in NFPA and acromegaly 11, 18. Growth hormone (GH) and testosterone replacement may reduce mortality in GH and Gn deficiencies, respectively 16, 19.…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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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

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“…TSP1 has been shown to be elevated in patients with peripheral vascular disease (30) and in patients with diabetes and coronary artery disease (18). This raises the question as to whether elevated TSP1 might be a risk factor for cardiovascular disease (31), which is the leading cause of morbidity and mortality in patients with endogenous or exogenous glucocorticoid excess (6,7,32,33,34,35).…”

Section: Discussionmentioning

confidence: 99%

“…Researchers have found a significant increase in the mortality of hypopituitary patients treated with R25-30 mg of hydrocortisone per day (6,7). When used in pharmacological doses (O5 mg/day of prednisolone or equivalent), glucocorticoids are potent anti-inflammatory agents and also have anti-neoplastic and immunosuppressive properties (8).…”

Section: Introductionmentioning

confidence: 99%

Thrombospondin-1 is a glucocorticoid responsive protein in humans

Barclay

Petersons

Keshvari

et al. 2016

European Journal of Endocrinology

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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.

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The Perioperative and Postoperative Care for Pituitary Patients

Khan

Salvatori

2017

Transsphenoidal Surgery

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Glucocorticoid Replacement and Mortality in Patients with Nonfunctioning Pituitary Adenoma

Abstract: Higher glucocorticoid replacement doses are associated with increased overall mortality in patients with NFPA and insufficiency of HPA axis. This further substantiates the importance of a balanced and adjusted glucocorticoid replacement therapy in these patients.

Cited by 84 publications

References 11 publications

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

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

The Perioperative and Postoperative Care for Pituitary Patients

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