Ezzat S, Ezrin C, Yamashita S, Melmed S
Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center-University of California, School of Medicine, Los Angeles 90048.
Cancer. 1993 Jan 1;71(1):66-70. doi: 10.1002/1097-0142(19930101)71:1<66::aid-cncr2820710112>3.0.co;2-u.
Acromegaly is usually the result of a pituitary growth hormone (GH)-cell adenoma or is more rarely due to ectopic secretion of GH-releasing hormone (GHRH). The authors previously described a more unusual form of acromegaly secondary to ectopic GH synthesis by a pancreatic islet cell tumor.
One year after tumor resection and transient disease remission, multiple abdominal metastases were identified with accompanying elevated levels of circulating GH and insulin-like growth factor-1 (IGF-1). Serial 24-hour GH sampling was performed before and after intravenous GHRH or thyrotropin releasing hormone (TRH) administration during treatment with bromocriptine; treatment with the somatostatin (SRIF) analogue octreotide; or no treatment. RNA from abdominal tumor tissue was extracted and subjected to Northern gel electrophoresis and GH hybridization analysis.
Neither GHRH nor TRH resulted in stimulation of the elevated GH levels. Bromocriptine and octreotide did not suppress GH secretion but attenuated the thyroid stimulating hormone (TSH) response to TRH administration. Octreotide (as much as 1500 micrograms/d) was clinically, biochemically, and radiographically ineffective. GH-secreting abdominal tumor tissue expressed a 0.9-kb mRNA transcript consistent with the size of authentic human GH mRNA.
The natural history and ectopic nature of a GH-producing pancreatic carcinoma has been documented, with biochemical remission occurring after initial tumor resection, with autonomous GH hypersecretion after tumor recurrence, and with RNA analysis demonstrating ectopic activation of GH gene transcription.
肢端肥大症通常是由垂体生长激素（GH）细胞腺瘤引起的，或更罕见地是由于生长激素释放激素（GHRH）的异位分泌。作者之前描述了一种更不寻常的肢端肥大症形式，继发于胰岛细胞瘤异位合成GH。
肿瘤切除和疾病短暂缓解一年后，发现多处腹部转移，伴有循环GH和胰岛素样生长因子-1（IGF-1）水平升高。在使用溴隐亭治疗期间，静脉注射GHRH或促甲状腺激素释放激素（TRH）前后进行连续24小时GH采样；使用生长抑素（SRIF）类似物奥曲肽治疗；或不进行治疗。从腹部肿瘤组织中提取RNA，进行Northern凝胶电泳和GH杂交分析。
GHRH和TRH均未刺激升高的GH水平。溴隐亭和奥曲肽未抑制GH分泌，但减弱了TRH给药后促甲状腺激素（TSH）的反应。奥曲肽（高达1500微克/天）在临床、生化和影像学上均无效。分泌GH的腹部肿瘤组织表达了一种0.9kb的mRNA转录本，与真实人类GH mRNA的大小一致。
已记录了产生GH的胰腺癌的自然病史和异位性质，初始肿瘤切除后出现生化缓解，肿瘤复发后出现自主性GH分泌过多，RNA分析显示GH基因转录的异位激活。
