Avgerinos P C, Chrousos G P, Nieman L K, Oldfield E H, Loriaux D L, Cutler G B
Developmental Endocrinology, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Endocrinol Metab. 1987 Nov;65(5):906-13. doi: 10.1210/jcem-65-5-906.
After surgical cure of Cushing's syndrome most patients develop transient secondary adrenal insufficiency that lasts for approximately 1 yr. Since ACTH-secreting pituitary adenomas generally respond to ovine CRH (oCRH), we tested the hypothesis that an early postoperative response to oCRH may indicate the presence of residual pituitary tumor and, therefore, predict recurrence. We also assessed the usefulness of oCRH for monitoring the recovery of the hypothalamic-pituitary-adrenal axis and for clarifying the pathophysiology of this condition. Thirty-four patients cured of Cushing's syndrome (29 with Cushing's disease, 3 with adrenal adenomas, and 2 with the ectopic ACTH syndrome) had an evening oCRH test 1-2 weeks after surgery. Nine patients (6 with Cushing's disease, 2 with adrenal adenomas, and 1 with the ectopic ACTH syndrome) participated in a longitudinal evaluation and had repeated oCRH and 1-h ACTH tests at 2-month intervals for a year after surgery. Patients were considered to be cured on the basis of at least 3 subnormal urinary [less than 20 micrograms/24 h (less than 55 nmol/day)] or morning plasma cortisol levels [0600-0900 h; less than 6 micrograms/dL (less than 170 nmol/L)] in the first 2 weeks after surgery. The plasma ACTH and cortisol responses to oCRH in the early postoperative period were subnormal in 23 and normal in 6 patients with Cushing's disease. Three patients developed recurrent Cushing's disease (3, 3, and 23 months after transphenoidal surgery). All 3 were among the 6 who had a normal early postoperative response to oCRH. All of the 23 patients who had a subnormal response to oCRH in the early postoperative period have remained in remission for an average follow-up period of 14 months (6-42 months). Thus, the recurrence rate was significantly greater in patients with normal oCRH tests in the early postoperative period (P less than 0.001, by chi 2 analysis). Surgically cured patients with adrenal adenomas or ectopic ACTH secretion also had subnormal plasma ACTH and cortisol responses to oCRH during the early postoperative period. During longitudinal evaluation for 12 months after surgery, the ACTH and cortisol responses to oCRH increased progressively (regardless of the cause of Cushing's syndrome). Cortisol responses to oCRH correlated significantly with the cortisol responses to exogenous ACTH (r = 0.89; P less than 0.00001). We conclude that most patients with Cushing's syndrome have suppressed responses to oCRH during the early postoperative period.(ABSTRACT TRUNCATED AT 400 WORDS)
库欣综合征手术治愈后,大多数患者会出现持续约1年的短暂性继发性肾上腺功能不全。由于分泌促肾上腺皮质激素(ACTH)的垂体腺瘤通常对羊促肾上腺皮质激素释放激素(oCRH)有反应,我们检验了这样一个假设:术后早期对oCRH的反应可能表明存在残留垂体肿瘤,因此可预测复发。我们还评估了oCRH在监测下丘脑 - 垂体 - 肾上腺轴恢复以及阐明该病症病理生理学方面的作用。34例库欣综合征治愈患者(29例库欣病、3例肾上腺腺瘤、2例异位ACTH综合征)术后1 - 2周进行了夜间oCRH试验。9例患者(6例库欣病、2例肾上腺腺瘤、1例异位ACTH综合征)参与了纵向评估,术后1年内每隔2个月重复进行oCRH和1小时ACTH试验。根据术后前2周至少3次尿[低于20微克/24小时(低于55纳摩尔/天)]或早晨血浆皮质醇水平[0600 - 0900时;低于6微克/分升(低于170纳摩尔/升)]判定患者已治愈。23例库欣病患者术后早期对oCRH的血浆ACTH和皮质醇反应低于正常,6例正常。3例患者(经蝶窦手术后3、3和23个月)出现复发性库欣病。这3例均在术后早期对oCRH反应正常的6例患者之中。术后早期对oCRH反应低于正常的23例患者平均随访14个月(6 - 42个月)均保持缓解状态。因此,术后早期oCRH试验正常的患者复发率显著更高(经卡方分析,P小于0.001)。肾上腺腺瘤或异位ACTH分泌所致库欣综合征手术治愈患者术后早期对oCRH的血浆ACTH和皮质醇反应也低于正常。术后12个月的纵向评估期间,对oCRH的ACTH和皮质醇反应逐渐增加(无论库欣综合征病因如何)。对oCRH的皮质醇反应与对外源性ACTH的皮质醇反应显著相关(r = 0.89;P小于0.00001)。我们得出结论,大多数库欣综合征患者术后早期对oCRH的反应受到抑制。(摘要截短至400字)