Several benefits in terms of pharmacological treatment of pituitary prolactin adenoma: 1. The importance of drugs as the treatment of choice for prolactin adenoma: The guidelines (2014 edition) clarify the indications for dopamine agonist (DA) drug therapy, while noting that drugs normalize prolactin levels and significantly reduce tumor size in the vast majority of patients, making drug therapy appropriate for tumors of all sizes, including aggressive large or giant prolactin adenomas [2]. Because drug therapy is usually effective in restoring vision in a short period of time, its results are comparable to those of surgical cross-visual decompression surgery. Therefore, patients with large adenomas with visual field loss are no longer considered neurosurgical emergencies, with the exception of acute stroke of the tumor that results in a dramatic loss of visual acuity, for which emergency decompression surgery is indicated. In particular, it should be noted that pharmacological treatment should be preferred for aggressive giant prolactin adenomas because surgery does not allow total removal of the tumor with high risk and mortality, and postoperative medication is still required to control prolactin levels [3]. Bromocriptine is widely used in China because it has been proven to be safe and effective, and it is relatively inexpensive and available in most medical sectors in the country. Compared to bromocriptine, cabergoline is easy to take (long duration of action, 2 doses in 1 week), has mild side effects and better efficacy (effective in bromocriptine-resistant cases treated with cabergoline [4]). Since there is a lack of cabergoline in mainland China, it is advisable to urge the introduction of cabergoline so that more patients can benefit. 2. Discontinuation issues: Since the drug is used as the treatment of choice, it involves the issue of when to discontinue the drug, and this issue has always troubled our clinicians. In 2003, the New England Journal of Medicine reported 105 cases of microadenoma and 70 cases of macroadenoma treated with cabergoline for more than 2 years, prolactin decreased to normal level, tumor disappeared or shrunk by more than 50% and did not involve the optic cross and cavernous sinus, and 69% of microadenoma and 64% of macroadenoma did not have elevated prolactin after 2~5 years of discontinuation. The remission rate was significantly higher in patients with residual tumor than in those with residual tumor [5]. However, a meta-analysis showed that only 25% of microadenomas and 16% of macroadenomas continued to maintain normal prolactin levels after discontinuation, and the recurrence rate was lower after discontinuation of long treatment duration and after discontinuation of carte blanche [6]. Therefore, it is safe to discontinue DA in patients with long-term normal prolactin (more than 2 years) and no evidence of tumor on MRI [5]. Discontinuation can be considered even after two years of normal prolactin and more than 50% reduction in tumor volume after low-dose DA treatment, if the optic cross and cavernous sinus are not involved [7]. Obviously, bromocriptine discontinuation will face a higher recurrence rate. It is important to note that discontinued patients need to be carefully followed up periodically to detect recurrence of hyperprolactinemia and tumor enlargement for timely re-treatment. 3. Focus on basic research of prolactin adenoma to explore new targets or new drugs: At present, most studies on molecular markers of pituitary adenoma are focused on tumor growth and reproduction, invasion and development, while studies on markers related to drug therapy are rarely updated [8]. The target of the action of cabergoline and bromocriptine is the dopamine type 2 receptor (D2R), and the expression of D2R on the surface of tumor cells determines the effect of drug therapy [9]. Previous studies have shown that inhibition of adenylate cyclase activity by DA agonist Gαi2 leads to a decrease in intracellular cAMP levels, which in turn inhibits gene transcription and prolactin synthesis, resulting in less prolactin secretion; it also causes endoplasmic reticulum and Golgi apparatus convolution, tumor cell crumbling necrosis and volume reduction [10-11]. of the two subtypes of D2R (long-chain D2L and short-chain D2S), their D2S expression plays a more important role in drug treatment [12]. Also, we confirmed this result in a rat model of transplanted tumors [13]. Bromocriptine and cabergoline induce apoptosis via D2S, and this apoptosis is mainly caused by activation of downstream caspases via ERK, JNK, and p38MAPK pathways [14-15]. In addition, nerve growth factor receptors have been shown to be related to drug treatment sensitivity [16], and our study showed that NGF upregulates D2S expression through its receptors, thereby increasing the sensitivity to drug treatment [17]. Recently, Prof. Yazhuo Zhang’s team screened and validated that low expression of PRB3 was associated with drug sensitivity by whole exon sequencing of six sensitive and six resistant prolactin adenomas [18]. Their team also demonstrated that the estrogen antagonist fulvestrant was effective in the treatment of prolactin adenomas at the cellular level and in vivo in animals [19-20]. In recent years, temozolomide trials for the treatment of invasive pituitary tumors, pituitary carcinomas, and drug-resistant prolactin adenomas have been reported in the literature, and the therapeutic efficacy was related to the expression of MGMT [21]. All of the above studies are actively exploring new targets related to the therapeutic sensitivity of prolactin adenoma drugs. For the 10-25% of bromocriptine resistant patients, the subsequent treatment is very tricky. Therefore, in order to further improve the therapeutic effect of bromocriptine and cabergoline, we need to investigate the new mechanisms of drug action; on the other hand, we need to enhance the understanding of prolactin adenoma disease itself and explore the pathogenesis and drug treatment sensitivity mechanisms, so as to find the targets for new drug development. Recently, Ning Guang’s team in Shanghai Key Laboratory of Endocrine Tumors found that the L205R hotspot mutation on PRKACA gene is closely related to adrenocortical adenoma occurrence, thus providing a good target for drug development [22]. This study provides a good reference for seeking new targets for the treatment of prolactin adenoma in the future. It is believed that with such a large platform as the China Pituitary Tumor Collaborative Group, the advantage of a large sample patient population in China, and the good opportunity of the issuance of this guideline, we will actively carry out multicenter cooperative research with the aim of making breakthroughs in both clinical and basic research of pituitary tumors. We believe that one day, not only prolactinomas but also all pituitary adenomas will enter the era of drug treatment.