Recurrence-related Factors Analysis Of Adrenocorticotropic Pituitary Adenoma After Transsphenoidal Surgery-Clinical Review And Immunohistochemical Study

Objective To investigate the recurrence-related clinical factors in patients with adrenocorticotropic pituitary adenoma-induced Cushing’s disease who underwent transsphenoidal surgery and to find out the most predictive one(s) among them. We compared the expressions of several proliferative and invasive biomarkers by Immunohistochemistry to find out the recurrence-related cellular characteristic and molecular phenotype, which facilitates exploring its underlying mechanism.Method We randomly reviewed60patients with definite-diagnosed Cushing’s disease who had confirmed adrenocorticotropic pituitary adenoma after transsphenoidal surgery from1990to2004in our hospital. All of them didn’t receive any relevant treatment before admission and had long-term follow-up. They were assigned to recurrence or non-recurrence group according to relevant standards. We retrospectively analysed the gender, age, course, mean diameter of tumor, preoperative and postoperative hormone levels and the conditions during surgery. Meanwhile, we mensurated the different expressions of Ki-67, matrix metalloproteinase9, pituitary tumor transforming gene and high mobility group AT-hook2by Immunohistochemistry in two groups.Result Among clinical factors, high-volume blood loss during surgery (generally>400ml) and high postoperative cortisol level were most predictive indices. The postoperative cortisol level over3.65ug/dl predict recurrence with75%sensitivity and66.7%specificity. Moreover, female, mean diameter larger or equal to1cm and ambiguous preoperative MRI also seemed to be related to recurrence. The expression of matrix metalloproteinase9was significantly high in recurrence group (P=0.022) and was strongly related to the interval of recurrence (P=0.007, CC=-0.354). The other three biomarkers showed no statistic difference in two groups.Conclusion The recurrence of adrenocorticotropic pituitary adenoma after transsphenoidal surgery was influenced by multiple factors. Minimize the blood loss during surgery probably prevent recurrence. High postoperative cortisol level probably predicts recurrence. Tumors with high expression of matrix metalloproteinase9were more invasive, which means more difficult to be cut off completely. They were vulnerable to recurrence with shorter disease-free interval. The patients who had related risk factors should be followed-up closely.