Barrande G, Pittino-Lungo M, Coste J, Ponvert D, Bertagna X, Luton J P, Bertherat J
Service des Maladies Endocriniennes et Métaboliques, Hôpital Cochin, Paris, France.
J Clin Endocrinol Metab. 2000 Oct;85(10):3779-85. doi: 10.1210/jcem.85.10.6870.
Conventional radiotherapy is usually indicated in acromegaly when surgery fails to normalize GH secretion. However, the benefits of radiotherapy are delayed. This has raised questions about the potency of this treatment for reaching the safe GH level of 2.5 microg/L and for normalizing insulin-like growth factor I (IGF-I) levels, both of which are currently recommended as the therapeutic goal. To evaluate the long-term hormonal and metabolic effects of radiotherapy in acromegaly, a retrospective analysis was undertaken studying 128 patients followed for 11.5+/-8.5 yr (mean +/- SD) in a single center. The preradiation GH levels decreased as a function of time to 50% at 2 yr, 20% at 5 yr, and 10% at 10 yr. Basal GH levels below 2.5 microg/L were obtained in 7% of the patients at 2 yr, 35% at 5 yr, 53% at 10 yr, and 66% at 15 yr. A basal GH level below 2.5 microg/L was associated with suppression of GH below 2 microg/L during an oral glucose tolerance test and normalization of IGF-I levels in 9 of 10 patients. Preradiation GH levels was the sole factor that could predict the delay in GH fall to below 2.5 microg/L (P = 0.008). At the last follow-up, IGF-I levels were normalized in 79% of the patients (37 of 47; mean follow-up, 15.0+/-11.3 yr). In the 32 patients presenting with diabetes mellitus, improvement of glucose tolerance was associated with lower GH levels after treatment (35+/-78 microg/L in the group of 13 patients still presenting diabetes; 9+/-12 microg/L in the group of 4 patients with glucose intolerance; 5+/-8 microg/L in the 14 patients with normal glucose tolerance; P = 0.04). Ten years after termination of radiotherapy gonadotroph, thyreotroph and corticotroph deficiencies were observed in 80%, 78%, and 82% of the patients, respectively. In conclusion, conventional radiotherapy can reduce GH levels below the optimal level of 2.5 microg/L and normalize IGF-I levels in acromegaly. However, the incidence of late hypopituitarism is high, and the delay to obtain this safe GH secretory status can be long, depending on the preradiation GH level. These parameters should be considered when adjuvant therapy is needed after surgery.
当手术未能使生长激素（GH）分泌恢复正常时，传统放疗通常用于肢端肥大症的治疗。然而，放疗的益处出现较迟。这引发了关于这种治疗方法在达到2.5微克/升的安全GH水平以及使胰岛素样生长因子I（IGF-I）水平恢复正常方面效果的疑问，目前这两个指标均被推荐作为治疗目标。为了评估放疗对肢端肥大症患者的长期激素和代谢影响，我们进行了一项回顾性分析，研究了在单一中心随访11.5±8.5年（均值±标准差）的128例患者。放疗前的GH水平随时间下降，2年时降至50%，5年时降至20%，10年时降至10%。2年时7%的患者基础GH水平低于2.5微克/升，5年时为35%，10年时为53%，15年时为66%。基础GH水平低于2.5微克/升与口服葡萄糖耐量试验期间GH低于2微克/升以及10例患者中有9例IGF-I水平恢复正常相关。放疗前的GH水平是预测GH降至2.5微克/升以下延迟时间的唯一因素（P = 0.008）。在最后一次随访时，79%的患者（47例中的37例；平均随访时间15.0±11.3年）IGF-I水平恢复正常。在32例患有糖尿病的患者中，葡萄糖耐量的改善与治疗后较低的GH水平相关（13例仍患有糖尿病的患者组中为35±78微克/升；4例葡萄糖不耐受患者组中为9±12微克/升；14例葡萄糖耐量正常患者组中为5±8微克/升；P = 0.04）。放疗结束10年后，分别在80%、78%和82%的患者中观察到促性腺激素、促甲状腺激素和促肾上腺皮质激素缺乏。总之，传统放疗可使肢端肥大症患者的GH水平降至2.5微克/升的最佳水平以下，并使IGF-I水平恢复正常。然而，晚期垂体功能减退的发生率很高，达到这种安全GH分泌状态的延迟时间可能很长，这取决于放疗前的GH水平。在手术后需要辅助治疗时应考虑这些因素。
