Meyer Emily Jane, Spangenberg Lucía, Ramírez Maria José, De Sousa Sunita Maria Christina, Raggio Victor, Torpy David James
Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
Endocrine and Diabetes Services, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia.
J Endocr Soc. 2021 Jun 22;5(9):bvab115. doi: 10.1210/jendso/bvab115. eCollection 2021 Sep 1.
Corticosteroid-binding globulin (CBG) is the main transport protein for cortisol, binding up to 90% in a 1:1 ratio. CBG provides transport of cortisol within the circulation and targeted cortisol tissue delivery. Here, we describe the clinically novel "CBG Montevideo" a pathogenic variant that results in a 50% reduction in plasma CBG levels. This was associated with low serum total cortisol and clinical features of hypoglycemia, exercise intolerance, chronic fatigue, and hypotension in the proband, a 7-year-old boy, and his affected mother. Previous reports of 9 human CBG genetic variants affecting either CBG concentrations or reduced CBG-cortisol binding properties have outlined symptoms consistent with attenuated features of hypocortisolism, fatigue, and hypotension. Here, however, the presence of hypoglycemia, despite normal circulating free cortisol, suggests a specific role for CBG in effecting glucocorticoid function, perhaps involving cortisol-mediated hepatic glucose homeostasis and cortisol-brain communication.
皮质类固醇结合球蛋白（CBG）是皮质醇的主要转运蛋白，以1:1的比例结合高达90%的皮质醇。CBG在循环系统中提供皮质醇的转运，并将皮质醇靶向递送至组织。在此，我们描述了临床上一种新的“CBG蒙得维的亚”致病变体，该变体导致血浆CBG水平降低50%。这与一名7岁男孩先证者及其患病母亲的血清总皮质醇水平低以及低血糖、运动不耐受、慢性疲劳和低血压的临床特征相关。先前关于9种影响CBG浓度或降低CBG-皮质醇结合特性的人类CBG基因变体的报道，概述了与皮质醇减少症、疲劳和低血压的减弱特征一致的症状。然而，在此病例中，尽管循环游离皮质醇正常，但低血糖的存在表明CBG在影响糖皮质激素功能方面具有特定作用，可能涉及皮质醇介导的肝脏葡萄糖稳态和皮质醇与大脑的通讯。
