PDF(Pubmed)
Abstract：
In a small number of cases, the development of ectopic residual adrenal lesions during embryogenesis causing Cushing\'s syndrome due to the production of excess cortisol has been reported. A 29-year-old woman was admitted to our hospital for fatigue and recent amenorrhea. Her plasma ACTH was <1.5 pg/mL, and her serum cortisol was 21.4 pg/mL after the 8 mg dexamethasone suppression test, revealing the presence of ACTH-independent Cushing\'s syndrome; however, her bilateral adrenal glands were atrophied. Abdominal CT revealed a 40-mm round tumor on the right renal hilum and remarkably accumulated 131I-labelled adosterol. CT and bone scintigraphy showed that 99mTc-methylene diphosphonate had accumulated in her dissymmetric skull at the right-frontoparietal region. The tumor on the right renal hilum was laparoscopically removed. Her cortisol levels rapidly decreased to below the normal range, and glucocorticoids were administered to rescue adrenal insufficiency. The resected tumor was yellowish in appearance and 4.5×3.0×2.8 cm in size. Immunohistochemical staining for SF-1, P450scc, CYP17A, CYP21A, and CYP11B1 indicated that this tumor produced cortisol. Exome sequencing analysis revealed that the GNAS heterozygous mutation (c.601C>T, p. Arg201Cys; accession number, NM_000516.5) was found in approximately 20% of the adrenal tumor sample. A mutation of GNAS, encoding the Gsα subunit that mediates GPCR signaling, causes the constitutive activation of adenylyl cyclase, resulting in hypersecretion of hormones regulated by the GPCR. GNAS mutation is one of the major genetic causes of cortisol-producing adrenal tumors independent of ACTH secretion. Considering the combination of GNAS mutation with one of the typical clinical triad characteristics, fibrous dysplasia of bone, we diagnosed this patient with McCune-Albright syndrome accompanied by ACTH-independent Cushing\'s syndrome caused by an ectopic residual adrenal tumor due to GNAS mutation. This case highlights that GNAS involves a previously unknown pathological mechanism in which inhibition of the natural elimination of remnant tissue leads to ectopic endocrine hypersecretion.
摘要：
在少数情况下，在胚胎发育过程中由于产生过量皮质醇而导致库欣综合征的异位残余肾上腺病变的发展已有报道。一名29岁的妇女因疲劳和近期闭经入院。她的血浆ACTH<1.5pg/mL，8mg地塞米松抑制试验后，她的血清皮质醇为21.4pg/mL，揭示了ACTH非依赖性库欣综合征的存在；然而，她的双侧肾上腺萎缩。腹部CT显示右肾门有一个40毫米的圆形肿瘤，并明显积累了131I标记的多甾醇。CT和骨闪烁显像显示99mTc-亚甲基二膦酸盐积聚在她的右额顶区域的不对称头骨中。腹腔镜下切除右肾门肿瘤。她的皮质醇水平迅速下降到低于正常范围，并给予糖皮质激素以挽救肾上腺功能不全。切除肿瘤外观微黄色，大小4.5×3.0×2.8cm。免疫组织化学染色SF-1，P450scc，CYP17A,CYP21A,CYP11B1表明该肿瘤产生皮质醇。外显子组测序分析显示GNAS杂合突变(c.601C>T，p.Arg201Cys；登录号，在大约20％的肾上腺肿瘤样品中发现了NM_000516.5）。GNAS的突变,编码介导GPCR信号传导的Gsα亚基，导致腺苷酸环化酶的组成型激活，导致GPCR调节的激素分泌过多。GNAS突变是产生皮质醇的肾上腺肿瘤的主要遗传原因之一，与ACTH分泌无关。考虑到GNAS突变与典型临床三联征之一的结合,骨纤维发育不良，我们诊断该患者患有McCune-Albright综合征，伴有ACTH非依赖性库欣综合征，这是由于GNAS突变导致的异位残留肾上腺肿瘤。这种情况突出表明，GNAS涉及先前未知的病理机制，其中抑制残留组织的自然消除导致异位内分泌分泌过多。
