MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Addenbrookes Treatment Centre, UK.
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
J Clin Endocrinol Metab. 2020 May 1;105(5):1427-34. doi: 10.1210/clinem/dgz277.
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.
To determine the impact of primary adrenal insufficiency (PAI) and glucocorticoid replacement on circulating GDF15 levels.
We measured circulating concentrations of GDF15 in a cohort of healthy volunteers and Addison's disease patients following steroid withdrawal. Significantly higher GDF15 (mean ± standard deviation [SD]) was observed in the Addison's cohort, 739.1 ± 225.8 pg/mL compared to healthy controls, 497.9 ± 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 ± SD) was observed between the groups with values of 491.0 ± 157.7 pg/mL, 427.0 ± 152.1 pg/mL and 360 ± 143.1 pg/mL, in the low, medium and high glucocorticoid replacement groups, respectively, P < .0001.
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.
GDF15 是一种应激诱导激素，作用于后脑，激活与建立厌恶反应和减少动物模型中食物摄入和体重相关的神经回路。厌食、体重减轻、恶心和呕吐是糖皮质激素缺乏的常见表现，我们假设糖皮质激素缺乏可能与 GDF15 水平升高有关。
确定原发性肾上腺功能不全（PAI）和糖皮质激素替代对循环 GDF15 水平的影响。
我们测量了一组健康志愿者和 Addison 病患者在类固醇停药后的循环 GDF15 浓度。Addison 组的 GDF15（平均值±标准偏差[SD]）明显更高，为 739.1±225.8 pg/mL，而健康对照组为 497.9±167.7 pg/mL（P=0.01）。我们在 3 个具有经典先天性肾上腺增生或 Addison 病的 PAI 队列中评估了氢化可的松替代对 GDF15 的影响；静脉内氢化可的松替代在所有组中均降低了 GDF15。我们在具有药理学介导的皮质醇缺乏症的健康志愿者中检查了 GDF15 对增加剂量的糖皮质激素替代的反应。在皮质醇替代剂量低、中、高的组中，GDF15（平均值±SD）分别为 491.0±157.7 pg/mL、427.0±152.1 pg/mL 和 360±143.1 pg/mL，存在剂量依赖性差异，P<0.0001。
GDF15 在糖皮质激素缺乏状态下增加，并通过糖皮质激素替代恢复。鉴于 GDF15 在后脑的作用部位及其对食欲的影响，需要进一步研究以确定 GDF15 在介导糖皮质激素缺乏常见的厌食和恶心中的作用。
