| 1.ObjectiveGrowth hormone pituitary adenoma is the most common cause of acromegaly and is a chronic progressive disease.Due to the hidden nature and complexity of the disease,patients often have systemic complications at the time of diagnosis leading to increased mortality.The mainstream treatment includes surgery,drug therapy and radiation therapy.Transsphenoidal resection of pituitary adenoma is the preferred treatment at present.Although current guidelines clarify the selection and effects of various treatment options,there is no consensus on how to combine surgery with drug or radiation therapy.The AACE Acromegaly Guidelines recommend early prediction of disease activity,pointing out that Postoperative Day 1 Growth Hormone(POD1 GH)is used as an early predictive marker,and the critical point of POD1 GH is 2 ng/mL.Domestic guidelines do not specify which predictive markers are used for clinical reference.Previous experience suggested that POD1 GH<1 ng/mL was a preliminary marker of surgical remission,and patients with high growth hormone level and invasive imaging manifestations had poor surgical effect.At present,a large number of studies have shown that preoperative drug therapy can improve the prognosis of patients with high GH,and early drug or radiotherapy can significantly control the symptoms and improve the prognosis of patients with poor surgical results.We hope to explore the factors that may affect the surgical effect of GH adenoma through retrospective analysis,observe the critical point of Preoperative GH and POD1 GH,and provide help for patients with poor surgical effect to choose adjuvant therapy before and after surgery.2.MethodsA retrospective analysis was performed on 70 patients with growth hormone pituitary tumors admitted to the Department of Neurosurgery,Qilu Hospital of Shandong University from January 2017 to December 2019.All patients were treated with endoscopic transsphenoidal pituitary adenoma resection.None of the patients received radiotherapy or drug therapy before surgery or within 12 weeks after surgery.The diagnosis of growth hormone pituitary adenoma was made according to preoperative clinical symptoms,pituitary hormone test and imaging examination.The general data,complications,imaging features,pathological features,preoperative hormone levels,postoperative hormone levels and postoperative follow-up results were summarized.The relationship between various factors and patient prognosis was analyzed.3.ResultsThe case data of 70 patients were collected,including 34 patients in the biochemical remission group and 36 patients in the non-biochemical remission group,with a postoperative biochemical remission rate of 48.6%.3.1 Baseline FeaturesThere were 32 males and 38 females,with an average age of 45.73±10.14 years.The mean BMI was 26.76±3.74.27 patients with hypertension,20 patients with type 2 diabetes,and 7 patients with sleep apnea syndrome.There were 65 large adenomas(diameter>10 mm)and 5 microadenomas(diameter<10 mm).The mean maximum diameter and volume of tumor were 1.94±0.90 cm and 3.61±9.94 cm3 respectively.12 Knosp grade 0,20 Knosp grade 1,10 Knosp grade 2,26 Knosp grade 3,and 2 Knosp grade 4.Tumor invasion of cavernous sinus in 33 patients,tumor compression of optic chiasma in 23 patients.Ki-67 index of 70 patients was 2.26±1.37%.Mean preoperative growth hormone level was 22.42 ±26.07 ng/mL,mean IGF-1 index(IGF-1 level/upper normal limit)was 1.63 ± 0.49.The average prolactin level was 30.15±56.99 ng/mL.3.2 Correlation data in variable analysisThe mean maximum tumor diameter of the biochemical remission group was 1.60±0.78 cm,and that of the non-biochemical remission group was 2.21±0.93 cm.The correlation between the maximum tumor diameter and biochemical remission was statistically significant(P<0.001).The mean tumor volume was 2.03±3.03 cm3 in the biochemical remission group and 5.05±13.42 cm3 in the non-biochemical remission group.The correlation between tumor volume and biochemical remission was statistically significant(P<0.001).According to Knosp grade,the number of grade 0,1,2,3 and 4 in the biochemical remission group was 11,13,5,5 and 0,the number of grade 0,1,2,3 and 4 in the biochemical non-remission group was 1,7,5,21 and 2.Knosp grade and biochemical remission were statistically significant(P<0.001).Knosp grade 0-2 is low invasiveness,and Knosp grade 3-4 is high invasiveness.In the biochemical remission group,29 cases and 5 cases in grade 0-2 and grade 3-4,respectively.In the non-biochemical remission group,13 cases and 23 cases in grade 0-2 and grade 3-4,respectively.There was statistical significance between the level of tumor invasiveness and biochemical remission(P<0.001).There were 12 cases of tumor invasion of cavernous sinus in the biochemical remission group and 21 cases in the non-biochemical remission group.There was a certain correlation between tumor invasion of cavernous sinus and biochemical remission(0.001<P=0.046<0.05).The mean preoperative level of GH was 11.49±15.12 ng/mL in the biochemical remission group and 33.79±29.62 ng/mL in the non-biochemical remission group,indicating a statistically significant difference between preoperative GH and biochemical remission(P<0.001).The average GH level in POD1 was 1.10±1.89 ng/mL in the biochemical remission group and 3.87±6.25 ng/mL in the non-remission group.There was statistical significance between POD1 GH and biochemical remission(P<0.001).3.3 Correlation data of univariate Logistic regression analysisMaximum tumor diameter(OR,0.341,95%CI,0.154-0.666,P=0.004),tumor invasion of cavernous sinus(OR,0.362,95%CI,0.143-0.885,P=0.028),tumor invasiveness(Knosp 0-2 vs 3-4)(OR,0.104,95%CI,0.033-0.290,P<0.001),preoperative GH(OR,0.941,95%CI,0.905-0.971,P<0.001),POD1 GH(OR,0.598,95%CI,0.385,0.834,P=0.009).Tumor maximum diameter,tumor invasivity(Knosp 0-2 vs 3-4),tumor invasion of cavernous sinus,and preoperative GH level were correlated with preoperative predicted biochemical response.POD1 GH was associated with postoperative prediction of biochemical remission.3.4 Correlation data of multi-factor Logistic regression analysisPreoperative GH(OR,0.950,95%CI,0.907-0.986,P=0.016),POD1 GH(OR,0.550,95%CI,0.339-0.795,P=0.006).GH can be used as a preoperative predictor of biochemical remission.POD1 GH can be used as a postoperative predictor of biochemical remission.3.5 ROC curve and AUC valuePreoperative GH was used to predict the ROC curve and AUC value of postoperative biochemical remission of GH adenoma.Preoperative GH:AUC was 0.821,95%confidence interval of AUC was(0.726-0.917),sensitivity was 86.8%,specificity was 73.8%,PPV was 75.0%,and NPV was 86.1%.The preoperative critical value of GH was 15.264 ng/mL.POD1 GH was used to predict the ROC curve and AUC value of postoperative biochemical remssion of GH adenoma.POD1 GH:AUC is 0.780,95%confidence interval of AUC is(0.677-0.884),sensitivity is 86.8%,specificity is 69.0%,PPV is 71.7%,NPV is 85.3%.The critical value of GH was 1.289 ng/mL.Conclusion1.The critical point of POD1 GH as an early predictive marker of postoperative biochemical remission of GH adenoma was 1.289 ng/mL.When POD1 GH<1.289 ng/mL,69.8%of patients achieved postoperative biochemical remission.A total of 7 patients with POD1 GH level in the range of 1 ng/ml-1.289 ng/mL,finally 12 weeks of retesting GH and IGF-1 reached the standard of biochemical remission.Patients with POD1 GH<1.289 ng/mL need not be rushed for drug or radiotherapy,and clinical symptoms and biochemical indicators can be observed for 2-3 months.2.Preoperative GH as a predictor of biochemical remission after surgical treatment,and the critical value was 15.264 ng/mL.When preoperative GH was less than 15.264 ng/mL,76.7%of patients achieved biochemical remission after surgery.Patients with preoperative GH>15.264 ng/mL have a low probability of achieving biochemical remission by surgery alone.So preoperative drug adjuvant therapy or early postoperative drug or radiation therapy can be considered to improve the prognosis. |
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