Li et al. Chinese Neurosurgical Journal (2020) 6:20 https://doi.org/10.1186/s41016-020-00202-4 中华医学会神经外科学分会 CHINESE MEDICAL ASSOCIATION CHINESE NEUROSURGICAL SOCIETY RESEARCH Open Access Risk factors for the incidence of apoplexy in pituitary adenoma: a single-center study from southwestern China Yao Li1, Yuan Qian2,3, Yisheng Qiao1, Xiaoxiang Chen1, Jiaotian Xu1, Chao Zhang1, Wei Wang1, Junjun Li1 and Xingli Deng1* Abstract Background: Although the incidence and clinical manifestations of pituitary apoplexy were reported by a few researches, the results are not consistent. This study aimed to explore the risk factors associated with an incidence of apoplexy in pituitary adenomas. Methods: The clinical information of 843 patients with pituitary adenoma from the Department of Neurological Surgery, 1st Affiliated Hospital of Kunming Medical University, was reviewed. The incidence, clinical manifestation, and potential risk factors for pituitary apoplexy were analyzed by a case-control study. Results: In total, 121 patients (14.4%) with macroadenoma were suffered from pituitary apoplexy. Headache, vomiting, and visual impairment are the top 3 symptoms for the pituitary apoplexy. Logistic regression results showed that the hypertension(hypertension vs non-hypertension OR = 2.765, 95%CI: 1.41~5.416), tumor type (negative staining vs. positive staining, OR = 1.501, 95%CI:1.248~5.235), and tumor size (diameter > 2 cm vs. diameter ≤ 2 cm, OR = 3.952, 95%CI:2.211~7.053) are independent factors associated with pituitary apoplexy. Conclusion: Our results indicate that the risk factors for the incidence of pituitary apoplexy depend mainly on properties of the tumor itself (tumor size and pathologic type) and the blood pressure of patients. Keywords: Pituitary adenoma, Pituitary apoplexy, Risk factors Background are observed in health centers: patients suspected with In 1950, the term “pituitary apoplexy” was first formally pituitary apoplexy may recover immediately without used to describe a fatal case of pituitary tumor- neurological and endocrinological deficiency or deterior- associated hemorrhage or infarction [1]. Patients suffer- ate intensely owing to mass effects and the secondary ing from pituitary apoplexy usually complain about an subarachnoid hemorrhage (SAH) [5]. Moreover, in some unexpected severe headache, sometimes visual deterior- cases, the tumor may be completely controlled after apo- ation [2, 3]. plexy while the remnants may continue to grow in other Acute apoplexy is unpredictable and complicated [4]. cases [6, 7]. Two distinct extreme manifestations of acute apoplexy Doctors including emergency physicians, ophthalmolo- gists, endocrinologists, and neurosurgeons are facing critical issues raised by the management of pituitary * Correspondence: [email protected] 1Department of Neurological Surgery, 1st Affiliated Hospital of Kunming apoplexy. However, rare studies about pituitary apoplexy Medical University, Kunming, China have been reported, and there is few evidence-based Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. Chinese Neurosurgical Journal (2020) 6:20 Page 2 of 6 strategies to manage these patients [8]. In the past, pitu- Hypertension is defined as taking hypertensive drugs itary apoplexy was treated as an emergence situation and or systolic blood pressure (≥ 140 mmHg) or diastolic immediate surgical intervention was preferable. Never- blood pressure (≥ 90 mmHg) [10]. Diabetes mellitus theless, conservative treatment is also desirable now- (DM) was diagnosed according to WHO diagnostic cri- adays [9]. Thus, the optimal management of pituitary teria in 1999 [11]. apoplexy remains a controversy. Identifying risk factors of pituitary apoplexy would do Imaging examination a favor for the management of pituitary apoplexy. To ex- All patients received a computed tomography (CT) and/ plore the risk factors associated with the incidence of pi- or magnetic resonance imaging (MRI) scan. Three- tuitary apoplexy, we reviewed and analyzed the clinical dimensional imaging provided by MRI shows the loca- information of 843 patients with pituitary adenomas tion and the degree of hemorrhage. (PA) from the Department of Neurological Surgery, 1st Affiliated Hospital of Kunming Medical University. Pathology examination Standard immunohistochemical staining was used to de- termine tumor types at the Department of Pathology, Methods The First Affiliated Hospital of Kunming Medical Patients attended at the Department of Neurological University. Surgery, 1st Affiliated Hospital of Kunming Medical University, and diagnosed with PA from 2013 to 2017 Statistical methods were included in our study. All patients had operations All quantity datas were analyzed by SPSS software either trans-sphenoidal microsurgery or craniotomy. (version 24.0). The main method is to compare the fre- Eight hundred forty-three patients aged from 15 to 82 quency distribution of each group by general statistical (mean, 45.0 ± 13.4 years) were recruited. The research description, Pearson’s chi-squared test, and Pearson’s had achieved authorization from the Ethics Committee statistic with a continuity correction. In order to evaluate of the First Affiliated Hospital of Kunming Medical the risk factors of pituitary apoplexy, logistic regression University. analysis was carried out to adjust the confounding fac- tors in the whole group of patients; Calculation sheet Data collection variables and the adjusted odds ratio (OR) and corre- Data on clinical features including sex, age, main com- sponding 95% confidence interval (CI). Two-tailed P plaint, clinical manifestation, results of imaging examin- values less than 0.05 were considered statistically ation, endocrine function tests, pathological results, and significant. medical history were obtained from the medical record database. Results Eight hundred forty-three patients (mean age: 45.0 ± 13.4 years) with PA were included in this study. Table 1 Cases and controls shows the clinical characteristics of these patients, and The factors influencing the incidence of pituitary apo- the tumor subtypes based on pathological results are plexy were studied by a matched case-control study. Pa- shown in Fig. 1. tients with pituitary apoplexy (case group) were contrasted with surplus PA patients without pituitary Incidence of pituitary apoplexy apoplexy (control group). Patients of the control group One hundred twenty-one (14.4%) PA patients, with a were selected by a computer-generated random selection mean age of 43.5 ± 14.3 years, suffered from pituitary scheme. Control patients were matched to case patients apoplexy, As showed in Table 2, there was no significant by age (cases: controls = 1:2). difference in the incidence of pituitary apoplexy between different ages (P = 0.993, Table 2). And pituitary apo- Diagnostic criteria plexy occurred approximately equal between men Patients with two or three of the following standards (7.82%) and women (6.52%). In addition, there was no were diagnosed with pituitary apoplexy: significant correlation between tumor size and pituitary apoplexy in unmatched patients(P = 0.276). 1. Obvious symptoms of pituitary apoplexy (for instance, sudden headache, or vomiting, or visual Clinical presentation impairment); Table 3 illustrated the comparison of clinical presenta- 2. Radiologic signs of hemorrhage; tion between pituitary apoplexy cases (n = 121) and con- 3. Intraoperative or pathological found hemorrhage; trols (n = 242). The top 3 common symptoms in Li et al. Chinese Neurosurgical Journal (2020) 6:20 Page 3 of 6 Table 1 Characteristics of patients with pituitary tumors (n = Table 2 The incidence of pituitary apoplexy 843, January 2008–December 2018) Characteristics Apoplexy(n = 121) % P Characteristics n % Age Age ≤ 35 33 3.91 0.993* ≤ 35 207 24.6 36~45 31 3.67 36~45 228 27.0 46~55 35 4.15 46~55 224 26.6 ≥ 56 22 2.61 ≥ 56 184 21.8 Gender Gender Female 66 7.82 0.228* Female 401 47.6 Male 55 6.52 Male 442 52.4 Tumor size Tumor size d ≤ 2 cm 38 4.50 0.276 d ≤ 2 cm 267 31.7 d > 2 cm 83 9.84 d > 2 cm 576 68.3 Diabetes mellitus 5 0.59 0.563* Diabetes mellitus 42 5 Hypertension 22 2.61 0.006* Hypertension 125 14.8 Pathological staining Pituitary apoplexy 121 14.4 Null 66 7.8 NA FSH-LH 113 13.4 pituitary apoplexy were headache, visual deterioration, PRL 118 14.0 and visual field defect. These three symptoms were also ACTH 35 4.2 the top 3 in patients without pituitary apoplexy. GH 49 5.8