In recent years, due to the progress of imaging, radiotherapy, research on drug treatment of pituitary adenoma, the maturation of transsphenoidal microsurgery and the application of neuroendoscopy, the choice of pituitary adenoma treatment methods tends to be diversified and the concept of individualized and comprehensive treatment is applied in clinical practice, which has significantly improved the treatment effect of pituitary adenoma. At present, the standardization of domestic treatment needs special emphasis.
1. Early diagnosis of pituitary adenoma
Popularizing the knowledge of pituitary adenoma among doctors and patients is still one of the keys to early diagnosis. MRI dynamic enhancement scan of the saddle area combined with clinical manifestations and endocrinological examination has significantly improved the detection rate and early diagnosis of microadenoma, which is especially valuable for the diagnosis of Cushing’s disease with microadenoma as the main cause.
2.The choice of treatment for pituitary prolactin adenoma
The application of dopamine agonists has had a revolutionary impact. Drug therapy represented by bromocriptine can be preferred in most cases. It can normalize blood PRL in 70%-80% of cases, restore menstruation in 80%-90% of patients, and reduce the size of the tumor by more than 25% within 3 months after the use of the drug. Therefore, large adenomas with visual impairment can also be treated with drugs, which can improve the vision of 80-90% of patients. Current second-generation drugs, such as long-acting carte blanche, require only 1-2 doses per week and have fewer side effects and better efficacy. However, there is no sufficient evidence to date to prove that it can cure pituitary adenoma, and long-term medication and regular monitoring are required. About 8% of cases have a poor response to the drug, and 10% of patients cannot tolerate its side effects, and these patients need surgery. Removal of pituitary microadenomas by experienced neurosurgeons via butterfly surgery can achieve essentially the same efficacy as drug therapy, and the view that surgery will result in loss of fertility is one-sided. Therefore, according to the national situation, transsphenoidal surgery is preferred for female patients who do not have fertility requirements, patients who do not want to take long-term medication or have financial difficulties, and patients who have concerns about living with tumors and actively request surgery. For patients with significant visual impairment, there is still disagreement as to whether drug or surgical treatment is preferred. In principle, medication can be used first, and if the improvement of visual function is not obvious, early surgery should be performed. We prefer to operate first to rapidly decompress the optic nerve and improve visual acuity, and then treat with medication if the tumor remains after surgery and the blood PRL is still high. For microadenomas without amenorrhea and breast overflow, their chances of continued growth are low, so they only need to be observed during follow-up and no treatment is necessary.
3.Treatment of acromegaly
At present, transsphenoidal surgery is still preferred. In terms of efficacy assessment, the criteria for cure should be that the blood GH level, GH glucose suppression test and IGF-1 are normalized. Octreotide (Sunnin and Sunlon, etc.) and lanotide have been widely used abroad, and blood GH and IGF-1 are normalized in 50%-70% of patients after treatment, and pituitary adenomas are small in 30% of cases, but long-term medication is required. This drug is expensive and difficult to be used in China. At present, it is advocated that patients with obvious respiratory and cardiac dysfunction can be treated with 3 months of Zanlon therapy if available to improve cardiopulmonary function to reduce the risk of anesthesia and surgery. For those whose endocrine indexes do not reach the standard of cure or tumor recurrence after surgery, drug treatment can be considered if conditions allow.
4.Management of large and giant pituitary adenoma
At present, 96% of pituitary adenomas can be operated via butterfly. Except for the obvious dumbbell type and the inverted gourd type where the inner part of the saddle is very small and the upper part of the saddle is large, transsphenoidal surgery is preferred. Postoperative MRI and endocrinological examination should be reviewed regularly. In case of large residual tumor, transsphenoidal or transcranial surgery or supplemental drug and radiation therapy (including γ-knife) can be performed as appropriate. For invasive adenoma, a combination of surgery, drug and radiation therapy is generally required. For invasive adenoma, a combination of surgery, drugs and radiotherapy is generally required. After surgery, we should strive to achieve normal hormone levels.
5.New progress of transsphenoidal microsurgery
Based on the transoral nasal butterfly surgery, expanding the scope of exposure (expanding the transsphenoidal approach) in order to remove the tumors developing anteriorly, posteriorly and laterally is a surgical technique with potential development. The following two points should be considered in its application.
(1) Weighing the advantages and disadvantages. That is, depending on the size of the tumor and the degree of invasion of adjacent structures, especially if it is clearly growing toward the cavernous sinus, whether it is worth risking damage to adjacent important nerves, blood vessels and brain structures to remove a tumor that is unlikely to be completely excised. In other words, the residual tumor can still be treated by other treatments, such as radiotherapy; whereas once neurological dysfunction occurs, it is irreversible, so the pros and cons need to be weighed.
(2) The experience of the operator and the condition of the equipment, do not do it rashly without great certainty.
6. About endoscopic resection of pituitary adenoma
Over the years, more experience has been accumulated. It can be used to see and remove the tumor in the dead corner of the surgical microscope and improve the surgical effect. The disadvantage is that it is a two-dimensional image, which requires longer training and practice to adapt and master; it is more difficult to stop bleeding when encountering obvious bleeding during surgery. Endoscopic surgery alone is not recommended for those with poor pneumatization of the pterygoid sinus. The surgical instruments currently used need further development and improvement. Personally, by comparing the technical operation and post-operative efficacy of endoscopic surgery alone and microscopic surgery alone, the authors believe that microscopic surgery currently has more advantages, and this advantage is mainly manifested in several aspects.
1. It is easier to distinguish pituitary adenoma tissue from normal pituitary tissue under direct vision, and it is easier to completely remove the tumor.
2. The operator can use both hands to operate the surgical instruments during the microscopic surgery, and the operation can be completed by a single person under normal circumstances, while most of the endoscopic surgery requires one hand to hold the endoscope, and only the other hand can be used to operate the surgical instruments, and the assistant is needed to help with other surgical instruments such as the suction device, so one hand is definitely not as dexterous as two hands. It is easier and more thorough to stop bleeding under direct vision.
3, from the perspective of minimally invasive, microscopic surgery can better protect the mucosa of the nasal cavity and the mucosa of the ventral wall of the pterygoid sinus, which can be anatomically reset, while endoscopic surgery is difficult to do.
However, the combined endoscopic and microscopic transsphenoidal pituitary adenoma resection can complement each other’s strengths and weaknesses, as it can be operated under direct vision on the one hand, and can be used to view dead corners that are difficult to see under the microscope on the other hand. However, this procedure can only be called “endoscopy-assisted transsphenoidal pituitary adenomectomy”, but not “complete endoscopic transsphenoidal pituitary adenomectomy.
7.Radiation therapy (including gamma knife)
At present, due to the progress of surgery and drug treatment and the application of γ-knife, the traditional external radiotherapy as adjuvant treatment needs to be strictly controlled to avoid radiation damage, aggravation of visual impairment and pituitary hypoplasia. γ-knife treatment has been developed, which can control tumor growth and reduce the hormone level of secretory pituitary adenoma. At present, it is mainly used as postoperative adjuvant therapy. At present, it is mainly used as postoperative adjuvant therapy.
8. Outlook
Large and giant invasive pituitary adenomas, especially non-functional adenomas, are still one of the problems in neurosurgery because of the difficulty of total excision, high recurrence rate and lack of effective drug treatment. Future research will focus on further improvement of transsphenoidal microsurgery techniques, such as the use of expanded transsphenoidal surgical access, promotion of navigation systems, intraoperative MRI and endoscopic techniques in transsphenoidal microsurgery, and improvement of transsphenoidal endoscopic surgical resection results through equipment and instrumentation. Given that there are still no effective drug treatments for non-functioning pituitary adenomas and ACTH adenomas, the development of drugs for these adenomas will be of great importance. gamma knife has definite efficacy and needs to be evaluated according to the requirements of evidence-based medicine. The future treatment of pituitary adenoma will be a combination of surgery, drugs and stereotactic radiosurgery based on the various treatment methods mentioned above, with surgery as the main treatment, according to the individualized requirements. In recent years, basic research on gene therapy for pituitary adenoma has made some progress, and with the in-depth research on the pathogenesis of pituitary adenoma and new molecular therapeutic targets, it is expected that gene therapy will become one of the important treatment methods for pituitary adenoma, but it will go through a long process to be really applied in the clinic.