背景：肢端肥大症是一种因血液中生长激素（Growth hormone, GH）及胰岛素样生长因子 1（Insulin like growth factor 1, IGF-1）浓度升高而出现的罕见进行性慢性疾病。该病最突出的临床表现除了手足四肢关节的增大和面容上的变化，还常合并代谢异常、呼吸系统疾病以及多系统功能紊乱。本病的治疗目标是降低血清中GH/IGF-1 水平，目前手术切除垂体肿瘤是该病的首选治疗方式，根据术后激素水平是否达标可辅以药物或放射等其它治疗。关于肢端肥大症患者手术前后体内高GH 水平和瘤体的占位效应对其它垂体前叶激素释放及垂体-靶腺轴影响的临床研究目前较少。目的：本研究通过分析肢端肥大症患者临床特征与垂体-靶器官轴线的关系，探讨经蝶入路垂体肿瘤切除术（Transsphenoidal surgery, TSS）前后垂体前叶激素水平与垂体-靶器官轴功能之间的关系。方法： 本研究为单中心、回顾性、观察性队列研究。 收集并统计了 2015.01-2018.12 北京协和医院神经外科收治的 652 例垂体生长激素腺瘤患者临床资料和随访至今的随访记录。使用 Excel、SPSS 及 Origin 软件对采集到的数据进行归类分析总结，进行包括非参数检验、独立危险因素分析、ROC 曲线绘制等分析。随访时间中位数为 51（3，98）月。结果：本研究中男性患者 290 例（44%），女性 362 例（55%）；确诊平均年龄 41.7 12.1 岁，病程平均 76  68 月；微腺瘤 114 例（17%），大腺瘤 538 例（83%） ；侵袭性（Knosp 分级为 III, IV）218 例（ 33%），非侵袭性（Knosp 分级为 I, II）434 例（67%）；术前 GH 随机值 34.8  74.9 ng/mL 血清 IGF-1 为 852  262ng/mL。本组男性患者术前垂体-性腺轴功能减退率为 40.1%（101/252），术后为 15.1%（包括新增2.0%（4/199）和术后未恢复 13.1%（26/199） ）；女性患者术前垂体-性腺轴功能减退率为 49.2%（90/183） ，术后为 34.0%（包括新增 3.8%（4/106）和术后未恢复32.0%（32/106） ）；术前垂体-甲状腺轴功能减退率为 6.1%（39/636） ，术后为 5.3%（包括新增 3.3%（17/509）和术后未恢复 2.0%（10/509） ）；术前垂体-肾上腺轴术前功能减退率为 5.2%（33/634），术后为 4.5%（包括新增 3.1%（15/489）和术后未恢复 1.4%（7/489） ） 。肿瘤侵袭海绵窦（p = 0.000）和术前血泌乳素值（p = 0.001）是术前肢端肥大症男性患者雄激素低下的独立危险因素，肿瘤是否侵袭海绵窦是术前预测肢端肥大症男性患者患垂体-性腺轴功能减退的最适单一因素，组织学染色/免疫组化泌乳素瘤阳性（p = 0.001）以及肢端肥大症缓解率（p = 0.006）是术后随访时肢端肥大症男性患者雄激素低下的独立危险因素，最适合预测术后男性肢端肥大症患者术后随访时雄激素是否低下状态的单一危险因素是患者的肢端肥大症管理状况；诊断年龄（p < 0.001） 、术前 GH 随机值（p = 0.005）和术前 GH 谷值（p = 0.022）是术前女性月经紊乱的独立危险因素，育龄期女性患者在确诊肢端肥大症时的年龄在协助诊断术前女性垂体-性腺轴功能减退方面是最适单一因素，术后肢端肥大症治疗状态与女性垂体-性腺轴、垂体-甲状腺轴和垂体-肾上腺轴无相关关系。患者的 BMI（p = 0.045） 、肿瘤侵袭海绵窦（p = 0.028） 、压迫视交叉（p = 0.001）和术前 IGF-1 水平（p < 0.001）是肢端肥大症患者术前甲状腺功能减退的独立危险因素。肿瘤压迫视交叉在协助诊断肢端肥大症患者术前垂体-甲状腺轴功能减退方面是最适单一因素。结论：垂体生长激素腺瘤导致的垂体-靶腺轴功能减退，其发生率依次为：女性垂体-性腺轴 > 男性垂体-性腺轴 > 垂体-甲状腺轴 > 垂体-肾上腺轴。TSS 有助于垂体-靶腺轴功能的恢复，其改善程度依次为：男性垂体-性腺轴 > 女性垂体-性腺轴 > 垂体-甲状腺轴 > 垂体-肾上腺轴。

Background: Acromegaly is a rare progressive chronic disease that occurs due to elevated concentrations of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in the blood. The most prominent clinical manifestations of acromegaly are enlargement of the joints in the hands, feet, and limbs, as well as changes in facial appearance. In addition, patients with acromegaly often have metabolic abnormalities, cardiovascular and respiratory and endocrine system disorders. The treatment goal of patients is to reduce excessive levels of GH and IGF-1 in the blood, mainly through surgical removal of pituitary tumors, supplemented by other treatment methods such as medical therapy or radiotherapy due to different patient requirements. There are currently few clinical studies on the effects of high GH levels in patients with acromegaly before and after surgery, as well as the space occupying effect of tumors, on the release of other anterior pituitary hormones and the pituitary target axis. Purpose: This large-sampled retrospective study focused on patients of Peking Union Medical College Hospital was designed to evaluate the relationship between characteristics of acromegaly and pituitary-organ axis both before and after transsphenoidal surgery .Methods: This was a single center, retrospective study. The relevant information and follow-up records of 652 patients with pituitary growth hormone adenoma admitted to neurosurgery department of Peking Union Medical College Hospital from January 2015 to December 2018 were collected and counted. Excel, SPSS, and Origin were used to analyze the collected data. Non-parametric tests, independent risk factor analysis, and ROC curve plotting were used to visualize and analyze data. Results: Mean diagnosed age (male 290, 44%; female 362, 55%): 41.7 12.1 years, disease duration: 76  68 months; microadenomas 114 cases (17%), macroadenomas 538 cases (83%).Invasion of cavernous sinus (Knosp grade III and IV) 218 cases (33%) and non-invasive (Knosp grade I and II) 434 cases (67%). Mean random GH: 34.8 74.9 ng/mL, mean serum IGF-1: 852 262ng/mL.Percentage of pituitary-gonadal axis hypofunction in male patients preoperatively was 40.1% (101/252) and 15.1% postoperative (new onset: 2.0% (4/199), remaining cases: 13.1% (26/199)). Percentage of pituitary-gonadal axis hypofunction in female patients preoperatively was 49.2% (90/183) and 34.0% postoperatively (new onset: 3.8% (4/199), remaining cases: 32.0% (32/106)).Percentage of pituitary-thyroid axis hypofunction preoperatively was 6.1% (39/636) and 5.3% postoperatively (new onset: 3.3% (17/509), remaining cases: 2.0% (26/509)). Percentage of pituitary-adrenal axis hypofunction preoperatively was 5.2% (33/634) and 4.5% postoperatively (new onset: 3.1% (15/489), remaining cases: 1.4% (7/489)). Invasion of cavernous sinus (p = 0.000) and preoperative PRL (p = 0.001) were independent risk factors of androgen deficiency in male patients. Invasion of cavernous sinus was the best single factor to predict pituitary-gonadal axis hypofunction in male patients preoperatively . histological staining for prolactinoma (+) (p = 0.001) and remission of acromegaly (p = 0.022) were independent risk factors for low androgen levels in male patients duringfollow-up. Remission of acromegaly was the best single factor for pituitary-gonadal axis hypofunction in male patients postoperatively. The age of diagnosis (p < 0.001), preoperative random GH (p = 0.005) and preoperative nadir GH (p = 0.022) were independent risk factors for menstrual disorders in women preoperatively . Age of diagnosis was the best single factor to predict pituitary-gonadal axis hypofunction in female patients preoperatively . BMI (p = 0.045), Invasion of cavernous sinus invasion (p = 0.028), compression of optic chiasm (p = 0.001) and preoperative IGF-1 (p < 0.001) were independent risk factors for preoperative hypothyroidism. Compressions of optic chiasm was the best single factor to predict pituitary-thyroid axis hypofunction preoperatively .Conclusions: Percentage of preoperative hypofunction: female pituitary-gonadal axis > male pituitary-gonadal axis > pituitary-thyroid axis > pituitary-adrenal axis. Remission rate after TSS: male pituitary-gonadal axis > female pituitary-gonadal axis > pituitarythyroid axis > pituitary-adrenal axis.