The classical term “pituitary apoplexy”  refers to a clinical syndrome characterized by abrupt onset of headache accompanied by neurologic or endocrinologic deterioration due to a sudden expansion of a mass within the sella turcica as a result of hemorrhage, infarction, or necrosis within a pituitary tumor and adjacent pituitary gland .
The incidence of pituitary apoplexy varies from 0.6 to 22% with different diagnostic criteria. Our study shows that 14.4% PA patients suffered from pituitary apoplexy, which is a little higher than some previous studies and may be related to the disparity in diagnosis. The diagnosis of pituitary apoplexy mainly bases on clinical presentations and imaging results. In this study, however, pituitary apoplexy was diagnosed on the basis of clinical signs couple with imaging, intra-operative, or histopathological findings [12,13,14,15,16].
The clinical presentation of pituitary apoplexy could be acute or subacute, depending on the amount of hemorrhage and its incidence speed. Usually, headache is the most frequent and earliest symptom of pituitary apoplexy, which is caused by the stimulation and stretching of the hypophyseal capsule or/and hemorrhage into subarachnoid space [17, 18]. Our study confirmed that 71.9% pituitary apoplexy patients present with a headache, which is consistent with previous studies. Besides, our study showed visual impairment was the second most common symptom of pituitary apoplexy, which is consistent with the previous report .
The risk factors for pituitary apoplexy are inconsistent between studies. The reported risk factors can be sort into categories: (1) reduced blood flow for the tumor, such as large tumor size; (2) acute increase in hypophyseal blood flow, including hypertension, diabetes, trauma, and increased intracranial pressure; (3) hormonal stimulation of the pituitary gland and tumor, for instance, endocrine stimulation tests, pregnancy, and exogenous estrogen therapy; (4) anticoagulated state, for example, anticoagulation, thrombolytic, and antiplatelet therapy [2, 16, 20,21,22]. Zhu et al. analyzed the incidence of pituitary apoplexy in 2021 PA cases and recognized male sex, non-function adenomas along with macroadenomas as risk factors for pituitary apoplexy .
Similar to the results of previous studies , our results show that the incidence of pituitary apoplexy in males(6.52%)is similar to females and is also very close between different age groups (Table 2), which means that sex and age are not independent risk factors for pituitary apoplexy.
Consistent with findings of previous studies [16, 20, 21, 23], the incidence of pituitary apoplexy is correlated with tumor size in our results. Pituitary apoplexy occurred near 4 times more often in large-sized tumors (diameter more than 2 cm) than small ones (diameter equal/less than 2 cm) (P = 0.000 < 0.05 OR:3.952, 95%CI:2.211~7.053). Therefore, we believe that tumor size is a risk factor for pituitary apoplexy.
It remains controversial whether the subtypes of PAs are a risk factor for the development of apoplexy. Previous studies reported that up to 45% of pituitary apoplexy were developed from non-function adenomas [2, 25]. However, a study demonstrated that secreting pituitary adenomas had a higher incidence of apoplexy . Similar to results by Zhu’s works , our study showed that the incidence of pituitary apoplexy is more common in pathological negative staining PA patients. The incidence of pituitary apoplexy in pathological negative staining adenoma is approximately 1.248~5.235 times higher than pathological positive staining adenomas, which means that the pathological negative staining of a tumor is an independent risk factor for pituitary apoplexy.
As it is thought, diabetes mellitus(DM)and arterial hypertension could affect the perfusion of microvasculature in the pituitary gland and pituitary adenoma [2, 27,28,29]. In our study, 2.61% and 0.59% of patients with pituitary apoplexy suffered from hypertension and DM, respectively. We found that hypertension is an independent risk factor for pituitary apoplexy through multivariate regression analysis with an OR of 2.765 (95%CI:1.411–2.231). However, it has not been proved that DM is associated with pituitary apoplexy.