Shi Y F, Harris A G, Zhu X F, Deng J Y
Department of Endocrinology, Peking Union Medical College Hospital, PR China.
Clin Endocrinol (Oxf). 1990 Jun;32(6):695-705. doi: 10.1111/j.1365-2265.1990.tb00916.x.
Ten patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open-label prospective trial of 3 daily subcutaneous injections of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201-995 doses were increased in a stepwise fashion from 100 micrograms every 8 h (three times daily) to 200, 300 and finally 500 micrograms three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12-h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 micrograms t.i.d. in 7/10 patients. Somatomedin-C (SM-C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201-995 up to 500 micrograms three times daily did not produce further clinically relevant GH or SM-C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side-effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 micrograms/day and one patient on 600 micrograms/day after 6-12 months treatment. This dose-finding study shows that 100 micrograms three times daily SMS 201-995 is an effective therapy for most of the acromegalic patients we treated.
10例活动性肢端肥大症患者（7例女性，3例男性）被纳入一项开放标签的前瞻性试验，其中5例曾接受过治疗，5例为新诊断患者。该试验为每日皮下注射3次长效生长抑素类似物SMS 201-995（善得定），剂量递增，以实现最大程度的生长激素（GH）抑制。4例患者曾接受过手术、放疗或溴隐亭治疗。若平均血清GH值在超过75%的样本中未能降至检测不到的水平，则SMS 201-995的剂量以逐步方式从每8小时100微克（每日3次）增至200、300微克，最终每月间隔增至每日3次500微克。最佳剂量维持长达28个月。所有患者的头痛、软组织肿胀、面部特征、多汗和感觉异常均有显著临床改善。4例患者的平均12小时GH水平显著受到抑制，4例降至正常水平。2例患者未实现GH水平的抑制。个体间平均GH值的比较表明，7/10的患者最佳有效剂量为每日3次100微克。在9例接受检测的患者中，生长调节素-C（SM-C）也显著降至治疗前水平的50%以下。随后将SMS 201-995增至每日3次500微克并未产生进一步的临床相关GH或SM-C抑制。5例患者出现垂体肿瘤缩小。甲状腺功能保持正常。4例患者出现糖耐量受损。副作用（腹泻、腹部不适）轻微且短暂。6至12个月治疗后，3例每日服用1500微克的患者和1例每日服用600微克的患者出现无症状胆结石。这项剂量探索研究表明，每日3次100微克的SMS 201-995对我们治疗的大多数肢端肥大症患者是一种有效的治疗方法。
