Gutt B, Hatzack C, Morrison K, Pöllinger B, Schopohl J
Department of Internal Medicine, Medizinische Klinik Innenstadt, University of Munich, Ziemssenstrasse 1, D-80336 Munich, Germany.
Eur J Endocrinol. 2001 Feb;144(2):109-16. doi: 10.1530/eje.0.1440109.
For patients in whom acromegaly persists despite pituitary surgery, conventional pituitary irradiation represents an additional treatment option. A 30-60% cure rate is described in the literature, but these studies did not utilise strict rules of remission, such as "safe" GH levels <2.5 microg/l, and age-adjusted normal IGF-I levels.
We report the outcome of 41 patients with acromegaly who received pituitary conventional external irradiation. The median follow-up time was 12.8 years (3.7-43.4 years) post-radiotherapy.
The median pre-irradiation GH level was 31.0 microg/l (7.0-210 microg/l). Information on IGF-I levels was only available for 6 patients prior to therapy. Utilising strict rules of remission, one-third (14/41) of our patients had normal biochemical parameters, i.e. "safe" GH (0.5 microg/l (range 0.2-1.6 microg/l)) and normal age-adjusted IGF-I levels (multiple of upper limit of normal range (xULN); 0.45 (0.2-1.0)) at the end of the follow-up period. An additional 9 patients achieved normal levels with adjunctive drug therapy. Furthermore, disease activity was reduced in a considerable proportion of the 18 patients who did not achieve normal biochemical levels (GH: 3.6 microg/l (1.9-15.7 microg/l); xULN of IGF-I: 1.6 (0.9-2.6)). In retrospect, remission is unlikely in patients who had a GH level greater than 52 microg/l (mean+2 s.d. of cured patients) prior to radiotherapy. In addition to the 12 patients with pre-irradiation pituitary functional deficiency, another 11 patients developed symptoms of panhypopituitarism during the 3-year period following irradiation. Within a 6-year period, partial pituitary insufficiency was observed in a further 7 patients, thus necessitating hormone substitution treatment.
Using strict rules of remission, in our cohort we found both a normalisation of IGF-I and safe GH levels in 34% of patients treated for acromegaly with conventional irradiation therapy.
对于垂体手术后仍存在肢端肥大症的患者,传统垂体放疗是一种额外的治疗选择。文献报道的治愈率为30%-60%,但这些研究未采用严格的缓解标准,如“安全”的生长激素(GH)水平<2.5μg/L以及根据年龄调整的正常胰岛素样生长因子-I(IGF-I)水平。
我们报告了41例接受垂体传统外照射的肢端肥大症患者的治疗结果。放疗后的中位随访时间为12.8年(3.7-43.4年)。
放疗前GH水平的中位数为31.0μg/L(7.0-210μg/L)。治疗前仅6例患者有IGF-I水平信息。采用严格的缓解标准,随访期末三分之一(14/41)的患者生化指标正常,即“安全”的GH水平为0.5μg/L(范围0.2-1.6μg/L)且根据年龄调整的IGF-I水平正常(正常范围上限的倍数(xULN);0.45(0.2-1.0))。另有9例患者通过辅助药物治疗达到正常水平。此外,在未达到生化指标正常的18例患者中,相当一部分患者的疾病活动度降低(GH:3.6μg/L(1.9-15.7μg/L);IGF-I的xULN:1.6(0.9-2.6))。回顾性分析发现,放疗前GH水平大于52μg/L(治愈患者的均值+2标准差)的患者不太可能缓解。除放疗前有垂体功能减退的12例患者外,另有11例患者在放疗后的3年期间出现全垂体功能减退症状。在6年期间,又有7例患者出现部分垂体功能不全,因此需要进行激素替代治疗。
采用严格的缓解标准,在我们的队列中,我们发现接受传统放疗治疗的肢端肥大症患者中有34%的患者IGF-I水平和安全的GH水平恢复正常。