학술논문
GDF15 Is Elevated in Conditions of Glucocorticoid Deficiency and Is Modulated by Glucocorticoid Replacement
CLINICAL RESEARCH ARTICLE
CLINICAL RESEARCH ARTICLE
Document Type
Report
Author
Source
Journal of Clinical Endocrinology & Metabolism. May 2020, Vol. 105 Issue 5, p1427, 8 p.
Subject
Language
English
ISSN
0021-972X
Abstract
GDF15 (then called MIC-1) was first identified in 1997 as a novel transcript from a macrophage cell line and classified as a member of the transforming growth factor beta (TGF-[beta]) [...]
Context: GDF15 is a stress-induced hormone acting in the hindbrain that activates neural circuitry involved in establishing aversive responses and reducing food intake and body weight in animal models. Anorexia, weight loss, nausea and vomiting are common manifestations of glucocorticoid deficiency, and we hypothesized that glucocorticoid deficiency may be associated with elevated levels of GDF15. Objective: To determine the impact of primary adrenal insufficiency (PAI) and glucocorticoid replacement on circulating GDF15 levels. Methods and Results: We measured circulating concentrations of GDF15 in a cohort of healthy volunteers and Addison's disease patients following steroid withdrawal. Significantly higher GDF15 (mean [+ or -] standard deviation [SD]) was observed in the Addison's cohort, 739.1 [+ or -] 225.8 pg/mL compared to healthy controls, 497.9 [+ or -] 167.7 pg/mL (P = 0.01). The effect of hydrocortisone replacement on GDF15 was assessed in 3 independent PAI cohorts with classical congenital adrenal hyperplasia or Addison's disease; intravenous hydrocortisone replacement reduced GDF15 in all groups. We examined the response of GDF15 to increasing doses of glucocorticoid replacement in healthy volunteers with pharmacologically mediated cortisol deficiency. A dose-dependent difference in GDF15 (mean [+ or -] SD) was observed between the groups with values of 491.0 [+ or -] 157.7 pg/mL, 427.0 [+ or -] 152.1 pg/mL and 360 [+ or -] 143.1 pg/mL, in the low, medium and high glucocorticoid replacement groups, respectively, P < .0001. Conclusions: GDF15 is increased in states of glucocorticoid deficiency and restored by glucocorticoid replacement. Given the site of action of GDF15 in the hindbrain and its effects on appetite, further study is required to determine the effect of GDF15 in mediating the anorexia and nausea that is a common feature of glucocorticoid deficiency. (J Clin EndocrinolMetab 105: 1427-1434, 2020) Key Words: glucocorticoids, adrenal insufficiency, GDF15
Context: GDF15 is a stress-induced hormone acting in the hindbrain that activates neural circuitry involved in establishing aversive responses and reducing food intake and body weight in animal models. Anorexia, weight loss, nausea and vomiting are common manifestations of glucocorticoid deficiency, and we hypothesized that glucocorticoid deficiency may be associated with elevated levels of GDF15. Objective: To determine the impact of primary adrenal insufficiency (PAI) and glucocorticoid replacement on circulating GDF15 levels. Methods and Results: We measured circulating concentrations of GDF15 in a cohort of healthy volunteers and Addison's disease patients following steroid withdrawal. Significantly higher GDF15 (mean [+ or -] standard deviation [SD]) was observed in the Addison's cohort, 739.1 [+ or -] 225.8 pg/mL compared to healthy controls, 497.9 [+ or -] 167.7 pg/mL (P = 0.01). The effect of hydrocortisone replacement on GDF15 was assessed in 3 independent PAI cohorts with classical congenital adrenal hyperplasia or Addison's disease; intravenous hydrocortisone replacement reduced GDF15 in all groups. We examined the response of GDF15 to increasing doses of glucocorticoid replacement in healthy volunteers with pharmacologically mediated cortisol deficiency. A dose-dependent difference in GDF15 (mean [+ or -] SD) was observed between the groups with values of 491.0 [+ or -] 157.7 pg/mL, 427.0 [+ or -] 152.1 pg/mL and 360 [+ or -] 143.1 pg/mL, in the low, medium and high glucocorticoid replacement groups, respectively, P < .0001. Conclusions: GDF15 is increased in states of glucocorticoid deficiency and restored by glucocorticoid replacement. Given the site of action of GDF15 in the hindbrain and its effects on appetite, further study is required to determine the effect of GDF15 in mediating the anorexia and nausea that is a common feature of glucocorticoid deficiency. (J Clin EndocrinolMetab 105: 1427-1434, 2020) Key Words: glucocorticoids, adrenal insufficiency, GDF15