Evaluation Of The Effects Of Pituitary Adenomas On Hormone Secretion In The Gonadal Axis And The Relevance Of Therapeutic Intervention

Objective: Normal gonadal axis hormone levels must be maintained to improve symptoms associated with male patients with pituitary adenoma.We evaluated the factors affecting testosterone in men with pituitary adenoma by surgical and pharmacological interventions to provide a basis for the optimization of treatment protocols.Methods: This was a single-center study that included a total of 423 male patients with nonfunctioning adenoma and prolactinoma diagnosed in our center between 2019 and 2021.Of these,90 patients were treated medically and 333 patients underwent surgery,17 of whom had combined coagulative necrotizing pituitary apoplexy.of the 316 patients without combined apoplexy,276 were patients with non-functioning adenomas and 40 were patients with prolactinomas.All patients were diagnosed and admitted for follow-up by the same experienced surgeon.Clinical data of the patients were collected for retrospective analysis.Results: A total of 91 of patients undergoing surgery without pituitary apoplexy had improved testosterone levels at the 3-month follow-up.In addition,tumor size was positively associated with low preoperative testosterone levels in patients with nonfunctioning pituitary adenomas(P< 0.05);hyperprolactinemia was associated with preoperative testosterone suppression(P < 0.05)."++++" grade invasion had a significant effect on the efficiency of testosterone recovery(P < 0.05).The 17 patients with combined coagulative necrotic pituitary apoplexy had worse recovery than other nonfunctioning adenomas at follow-up(P < 0.05).In addition,among the 90 patients taking bromocriptine,the rate of testosterone improvement was significantly higher in the drug-sensitive group after 6 months of treatment(P < 0.05).There may be a trend toward an increased rate of testosterone improvement in the drug-sensitive group compared with patients with poor prolactin recovery.Conclusions: The transsphenoidal pseudocapsule technique can achieve the desired rate of testosterone improvement while allowing a high retention of anterior pituitary function.Reduction in tumor size,normalization of prolactin,and excision of CNPA can improve testosterone levels separately or in combination.PART 1:Evaluation of intervention of pituitary-gonadal axis hormones in male pituitary adenoma patients by extra-pseudocapsule transsphenoidal surgery Objective: Maintenance of normal gonadal axis hormone levels is important to improve symptoms associated with male pituitary adenoma patients.The current literature contains mixed evaluations of gonadal axis function after surgical treatment of pituitary adenomas and few studies on the effects of extra-pseudocapsule resection technique on gonadal hormone intervention.In this study,we hope to evaluate the mechanism of the effect of pituitary adenoma on gonadotrophic hormones and the efficacy of surgery on male gonadotrophic hormones based on the clinical data from our center,and to elucidate the effectiveness and safety of the extra-pseudocapsule transsphenoidal technique on gonadotrophic hormone therapy in male patients.This will provide a basis for further optimization of the surgical treatment plan for pituitary adenoma.Methods: A total of 316 patients who underwent initial transsphenoidal surgery in the Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,between September 2019 and December 2021 were selected,and the tumor types included non-functional pituitary adenoma(276 cases)and prolactin adenoma(40 cases).All patients underwent resection of pituitary adenomas by the same experienced surgeon using a extra-pseudocapsule technique.The clinical data of the patients were collected for retrospective analysis to compare various indicators such as changes in hormone levels of the patients.Results: At 3-month follow-up after surgical treatment,testosterone levels improved in 91(28.8%),remained at preoperative levels in 222(70.3%),and deteriorated in 3(0.9%)compared to preoperative levels.Tumor size was positively correlated with preoperative testosterone levels in patients with non-functioning pituitary adenomas.74(26.81%)had improved testosterone levels after transsphenoidal surgery,and the vast majority of patients maintained normal other anterior pituitary functions.hyperprolactinemia was associated with preoperative testosterone suppression,and 17 patients(42.50%)had improved testosterone level after surgical treatment of patients with prolactin adenoma,among which the PRL returned to normal.The rate of testosterone improvement was significantly higher in patients with normalized PRL(66.67% vs.22.73%,P=0.02).On the other hand,the rate of testosterone improvement in tumors with high invasive rating,especially in "+++" grade tumors,decreased significantly in both NFPAs and prolactinomas.Conclusion: Removal of pituitary adenomas using the extra-pseudocapsule technique not only preserves normal pituitary structure and function,but also improves the hormonal abnormalities of the gonadal axis in men with pituitary adenomas by relieving the effects of compression;the more desirable the decrease in prolactin levels,the higher the testosterone improvement rate,provided that surgical decompression is adequate.In addition,increased tumor aggressiveness also leads to lower postoperative testosterone improvement rates.PART 2:Assessment of the effect of coagulative necrotic pituitary apoplexy on gonadal hormones in male patients with non-functioning adenomas before and after transsphenoidal surgery Objective: pituitary apoplexy is a rare and potentially life-threatening clinical syndrome.Coagulative necrotic pituitary apoplexy(CNPA)is generally considered a clinical subtype of ischemic pituitary stroke.In clinical practice,we have found that patients with CNPA may have more difficulty in recovering gonadotropic hormones than patients with pituitary adenomas in general,and the effect of CNPA on gonadotropic hormones in male patients before and after surgery is currently controversial This part of the study was designed to evaluate the effect of CNPA on the outcome of surgical treatment in male pituitary adenoma patients.Methods: A total of 293 male patients with non-functional adenoma who underwent initial transsphenoidal pituitary adenoma resection in the Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,between September 2019 and December 2021,of whom 17 were patients with combined CNPA and 276 were non-CNPA patients,were selected.The clinical data of the patients were collected to study the clinical characteristics of CNPA and its effects on the patients’ gonadal hormones,as well as to compare and analyze the gonadal regression with that of other patients with non-functional adenoma by propensity score matching.Results: Preoperative testosterone levels were low in 14 of 17 patients(82.35%)with nonfunctioning pituitary adenomas in men with CNPA,which was significantly lower than the proportion of low levels in general nonfunctioning adenomas(41.67%).Mean testosterone levels were also significantly worse(0.96 vs 2.22 ng/m L,P=0.001).at 3-month follow-up,there was no significant difference between follow-up testosterone levels and preoperative levels(1.10 vs 0.96 ng/m L,P=0.05),but CNPA patients had a significantly lower rate of testosterone improvement compared with the general population(5.88% vs32.35%,P< 0.05)and a significantly higher rate of worsening(17.65% vs 0.00%,P < 0.05).Conclusion: In male patients with non-functioning adenomas,the effects of CNPA on gonadal hormones are more severe than those of pituitary adenomas in general.After surgical treatment,patients with CNPA have a lower rate of improvement in testosterone levels and a higher rate of deterioration,and the overall treatment effect on gonadal hormones is significantly worse than in patients with general pituitary adenomas for 3months after surgery,and may show better results with longer follow-up.PART 3:Evaluation of the effect of bromocriptine intervention on gonadal hormones in male patients with prolactinoma Objective: Prolactinomas are the most common functional pituitary adenoma.About half of male patients with prolactinomas present to the clinic with symptoms of hypogonadism,and drug therapy is the first-line treatment for pituitary prolactinomas.This part of the study hopes to compare testosterone recovery in prolactinoma with different drug sensitivities by standardizing the follow-up time and evaluation criteria for testosterone regression,as well as to further explore the intervention effect of decreased prolactin on testosterone recovery.Methods: A total of 90 male patients with prolactinoma who attended the neurosurgery outpatient clinic and maintained follow-up at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,from September 2019 to December 2021 were retrospectively analyzed.The clinical data of the patients,including age,disease duration,hormones before and after treatment,and magnetic resonance imaging,were collected for statistical analysis.Results: Of the 90 patients with male prolactinoma,57(63.33%)were in the drug-sensitive group,of whom 40(70.18%)had low testosterone levels,and 33(36.67%)were in the druginsensitive group,of whom 26(78.79%)had low testosterone levels.After 6 months of bromocriptine treatment,32 patients(35.56%)with low testosterone levels remained,and the rate of testosterone improvement was significantly higher in the drug-sensitive group than in the drug-insensitive group(54.39% vs.13.93%).In the drug-insensitive group,there was no statistical difference in the testosterone improvement rate between patients with suboptimal PRL decline and those with suboptimal tumor shrinkage,and there was a trend of higher testosterone improvement rate in the drug-sensitive group compared with the PRLinsensitive group when tumor shrinkage was ideal(54.39% vs 42.86%).Conclusion: Drug therapy has a satisfactory intervention effect on testosterone outcomes.Different drug sensitivities resulted in different testosterone treatment outcomes,with significantly higher rates of testosterone improvement in drug-sensitive men with prolactinomas.Both PRL and tumor size changes can influence testosterone changes,and the decrease in PRL tends to increase the rate of testosterone improvement before and after drug treatment with a significant decrease in tumor size.