Besser G M, Mortimer C H, Carr D, Schally A V, Coy D H, Evered D, Kastin A J, Tunbridge W M, Thorner M O, Hall R
Br Med J. 1974 Mar 2;1(5904):352-5. doi: 10.1136/bmj.1.5904.352.
Growth hormone release inhibiting hormone (GHRIH) was administered by constant infusion over 75 minutes to eight acromegalic patients at different doses. 100 to 1,000 mug were equally effective in reducing circulating growth hormone (GH) levels; 25 mug lowered GH levels in only five patients, and at this dose the extent of the fall was smaller than from doses of 100 mug or more. 10 mug was ineffective. Injection of single doses of 500 mug by intravenous, subcutaneous, and intramuscular routes caused only small and transient reductions in GH levels, though the effect was improved by injecting the hormone intramuscularly in 2 ml of 16% gelatin. Injection of a suspension of 4 mg GHRIH in 1 ml of arachis oil lowered growth hormone levels for between three and four hours.In four acromegalic patients an oral 50-g glucose tolerance test was performed during a continuous infusion of either saline or 1,000 mug GHRIH. The "paradoxical" rise in growth hormone seen in these patients during the saline infusion was suppressed by GHRIH. The blood glucose responses were, moreover, modified by GHRIH in that the peak was delayed and occurred at the end of the infusion in each case. A "normal" glucose tolerance curve was converted to a "diabetic" type of response in two patients. This effect could be accounted for by the inhibition of insulin secretion known to occur with large doses of GHRIH.We speculate that acromegaly may be primarily a hypothalmic disease due to deficiency of GHRIH resulting in excessive secretion of growth hormone from the pituitary and adenoma formation due to inappropriate and prolonged stimulation of the pituitary.
向8例肢端肥大症患者以不同剂量持续输注生长抑素释放抑制激素(GHRIH)75分钟。100至1000微克在降低循环生长激素(GH)水平方面同样有效;25微克仅使5例患者的GH水平降低,且在此剂量下降低幅度小于100微克及以上剂量。10微克无效。静脉、皮下和肌肉注射单剂量500微克仅引起GH水平短暂小幅降低,不过将激素溶于2毫升16%明胶中肌肉注射可增强效果。将4毫克GHRIH悬浮于1毫升花生油中注射可使生长激素水平降低3至4小时。对4例肢端肥大症患者在持续输注生理盐水或1000微克GHRIH期间进行了口服50克葡萄糖耐量试验。这些患者在输注生理盐水期间出现的生长激素“反常”升高被GHRIH抑制。此外,GHRIH改变了血糖反应,使峰值延迟,且在每种情况下均在输注结束时出现。2例患者的“正常”葡萄糖耐量曲线转变为“糖尿病”型反应。这种效应可能是由于大剂量GHRIH已知会抑制胰岛素分泌所致。我们推测肢端肥大症可能主要是一种下丘脑疾病,由于GHRIH缺乏导致垂体生长激素分泌过多,以及垂体因不适当和长期刺激而形成腺瘤。