Imaki T, Tsushima T, Hizuka N, Odagiri E, Murata Y, Suda T, Takano K
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Japan.
Endocr J. 2001 Feb;48(1):53-62. doi: 10.1507/endocrj.48.53.
Transsphenoidal surgery is the treatment of choice for ACTH-producing pituitary adenoma (Cushing's disease) and pituitary irradiation is widely considered the most appropriate treatment for patients with Cushing's disease for whom transsphenoidal surgery has been unsuccessful. We studied 49 consecutive patients who underwent transsphenoidal surgery for the treatment of Cushing's disease at Tokyo Women's Medical University from 1977-1997 with a mean follow-up duration of 87.6 months (range, 24-253 months). We examined the relationship between postoperative endocrinological data, assessed between 3 and 8 weeks after surgery, and long-term outcome and efficacy of pituitary irradiation after surgery. Long-term remission was defined as the regression of the symptom and signs of Cushing's syndrome, and restoration of normal levels of plasma ACTH, cortisol and urinary free cortisol, together with adequate suppression of morning plasma cortisol levels following the administration of low dose (1 mg) of dexamethasone. Thirty patients had no additional treatment after pituitary surgery. Only 1 of 25 patients (4%) whose postoperative plasma cortisol level was less than 2 microg/dl developed recurrent disease whereas 3 out of 5 patients with postoperative plasma cortisol levels higher than 2 microg/dl relapsed. Postoperative external pituitary radiation was used to treat the remaining 19 patients. Four patients who received radiation therapy had a low or undetectable postoperative plasma cortisol level (<2 microg/dl, 56 nmol/L) and all of these patients developed hypopituitarism whereas 5 patients with subnormal plasma cortisol levels (2.0-10.0 microg/dl) remained in remission. Among 10 patients with persistent disease after surgery, 6 entered remission 6-47 months after irradiation but one of them subsequently relapsed after 108 months. These results suggest that 1) additional therapy should be avoided in patients with a postoperative plasma cortisol less than 2 microg/dl because relapse is very rare and radiotherapy will frequently induce hypopituitarism, 2) patients with a subnormal cortisol level following surgery should be treated with pituitary irradiation, because the relapse rate is reportedly high and radiotherapy is effective in preventing relapse, 3) radiotherapy in patients with persistent disease after surgery is effective only in 50% (5/10) of the patients.
经蝶窦手术是分泌促肾上腺皮质激素垂体腺瘤（库欣病）的首选治疗方法，而垂体放疗被广泛认为是经蝶窦手术失败的库欣病患者最适宜的治疗方法。我们研究了1977年至1997年在东京女子医科大学接受经蝶窦手术治疗库欣病的49例连续患者，平均随访时间为87.6个月（范围24至253个月）。我们检查了术后3至8周评估的内分泌学数据与术后垂体放疗的长期结局和疗效之间的关系。长期缓解定义为库欣综合征的症状和体征消退，血浆促肾上腺皮质激素、皮质醇和尿游离皮质醇水平恢复正常，以及给予低剂量（1毫克）地塞米松后早晨血浆皮质醇水平得到充分抑制。30例患者垂体手术后未接受其他治疗。术后血浆皮质醇水平低于2微克/分升的25例患者中只有1例（4%）复发，而术后血浆皮质醇水平高于2微克/分升的5例患者中有3例复发。其余19例患者接受了术后垂体外部放疗。4例接受放疗的患者术后血浆皮质醇水平低或检测不到（<2微克/分升，56纳摩尔/升），所有这些患者均出现垂体功能减退，而5例血浆皮质醇水平低于正常（2.0至10.0微克/分升）的患者仍处于缓解状态。在10例术后持续存在疾病的患者中，6例在放疗后6至47个月进入缓解期，但其中1例在108个月后复发。这些结果表明：1）术后血浆皮质醇低于2微克/分升的患者应避免额外治疗，因为复发非常罕见，放疗经常会诱发垂体功能减退；2）术后皮质醇水平低于正常的患者应接受垂体放疗，因为据报道复发率高，放疗对预防复发有效；3）术后持续存在疾病的患者放疗仅对50%（5/10）的患者有效。
