Melmed S, Ziel F H, Braunstein G D, Downs T, Frohman L A
Department of Medicine, Cedars-Sinai Medical Center, University of California School of Medicine, Los Angeles 90048.
J Clin Endocrinol Metab. 1988 Aug;67(2):395-9. doi: 10.1210/jcem-67-2-395.
A 59-yr-old woman with a disseminated carcinoid tumor was evaluated for acromegaly. She had previously undergone a hypophysectomy for acromegaly and an enlarged pituitary, with a reduction in her serum GH levels from 100 to 4 micrograms/L. Recurrence of acromegalic symptoms 2 yr later was accompanied by elevated serum GH (16 micrograms/L) and insulin-like growth factor I (IGF-I; 528 micrograms/L) and plasma GHRH levels (12 micrograms/L; normal, less than 30 ng/L). Computed tomographic scan did not reveal pituitary enlargement. Metastatic carcinoid tissue in bone removed at biopsy contained GHRH (100 pg/mg tissue). High performance liquid chromatography of plasma GHRH revealed predominantly GHRH-(3-40)-OH, a biologically inactive GHRH metabolite, along with mature GHRH forms, while carcinoid tissue contained both GHRH-(1-40)-OH and GHRH-(1-44)-NH2. Treatment with pergolide initially resulted in reduction in serum GH and IGF-I levels and amelioration of symptoms of acromegaly. However, after 14 months of pergolide therapy, serum GH levels increased despite administration of up to 1000 micrograms pergolide/day. Plasma GHRH levels remained elevated throughout the treatment period. Subsequent treatment with SMS 201-995, a long-acting somatostatin analog, for over 1 yr resulted in sustained reductions of ectopic GHRH secretion, GH hypersecretion, and IGF-I levels. Plasma GHRH levels correlated with simultaneously measured serum GH levels in response to acute SMS 201-995 administration. SMS 201-995 was an effective medical treatment for acromegaly caused by ectopic GHRH production in this patient.
一名患有播散性类癌瘤的59岁女性接受了肢端肥大症评估。她之前因肢端肥大症和垂体增大接受过垂体切除术，血清GH水平从100微克/升降至4微克/升。2年后肢端肥大症症状复发，同时血清GH（16微克/升）、胰岛素样生长因子I（IGF-I；528微克/升）和血浆GHRH水平（12微克/升；正常，低于30纳克/升）升高。计算机断层扫描未显示垂体增大。活检时切除的骨转移类癌组织含有GHRH（100皮克/毫克组织）。血浆GHRH的高效液相色谱分析显示，主要为生物活性不高的GHRH-(3-40)-OH代谢物以及成熟的GHRH形式，而类癌组织同时含有GHRH-(1-40)-OH和GHRH-(1-44)-NH2。培高利特治疗最初导致血清GH和IGF-I水平降低，肢端肥大症症状改善。然而，培高利特治疗14个月后，尽管每天给予高达1000微克培高利特，血清GH水平仍升高。整个治疗期间血浆GHRH水平一直升高。随后使用长效生长抑素类似物SMS 201-995治疗1年多，导致异位GHRH分泌、GH分泌过多和IGF-I水平持续降低。急性给予SMS 201-995后，血浆GHRH水平与同时测量的血清GH水平相关。SMS 201-995是治疗该患者由异位GHRH分泌引起的肢端肥大症的有效药物。
