Hyperprolactinemia (HPL) is a condition in which serum prolactin (PRL) levels are significantly higher than normal for various reasons, with hypogonadism, lactation and infertility as the main manifestations; it is the most common endocrine disorder with abnormalities in the hypothalamic-pituitary axis (HPA) and is common in women of childbearing age. PRL is a stress hormone, and its serum levels vary greatly during various physiological conditions and stress, and is the most influential of the pituitary hormones, with the most fluctuating serum levels. Like other pituitary hormones, PRL has a circadian rhythm, rising gradually after sleep, peaking about 1 h before awakening, and gradually declining after waking to a trough value at 2 p.m. Therefore, daytime secretion is lower than nighttime secretion. The normal value of PRL measured by marker immunoassay is 1-25 μg/L for women and 1-20 μg/L for men, with slight differences in different laboratories. [Etiology PRL secretion is regulated by the hypothalamic PRL-releasing factor (PRF) and PRL-releasing inhibitory factor (PIF), and the normal DA release from peptidergic neurons in the arcuate nodule of the hypothalamus is a PIF with predominant tonic inhibition. Any factors that interfere with hypothalamic DA synthesis and DA transport from the pituitary portal system to the pituitary, as well as DA binding to the DA receptor (D2) of PRL cells (this specific binding can inhibit PRL secretion and release) can weaken the inhibitory regulation and cause HPL, which can be classified into four categories: physiological, pathological, pharmacological and idiopathic. (i) Physiological Many physiological factors can cause a transient increase in PRL: elevated estrogen levels during ovulation and pregnancy inhibit the effect of DA on PRL cells, while increased estrogen levels during late pregnancy prompt PRL cells to secrete large amounts of PRL (up to 10 times higher than normal), thereby promoting lactation; nipple stimulation (during lactation) directly prompts pituitary PRL secretion; in addition, excessive physical exercise, hypoglycemia, late sleep, and mental trauma can cause HPL, In addition, excessive physical exercise, hypoglycemia, late sleep, psychological trauma, and 2-3 months after the birth of an infant can cause a physiological increase in PRL, which is often mildly elevated (<100μg/L) and fluctuates downward. (ii) Pharmacological Enhancement of PRF or antagonism of PIF substances can weaken the tension inhibition of DA, such as estrogen (including drug avoidance, especially long-term use), TRH and vasoactive intestinal peptide (VIP); various DA antagonists such as phenothiazines (e.g. chlorpromazine, endorphin); butylphenols (e.g. haloperidol) and other antipsychotics; tricyclics (e.g. promethazine, chlorpromazine, amitriptyline, clopidogrel) and Antidepressants such as monoamine oxidase inhibitors (e.g., phenelzine); H2 receptor blocking agents such as cimetidine for intravenous use; cardiovascular drugs such as verapamil, methyldopa, rifampin, glycyrrhiza, metoclopramide and sulpiride, opiates, and some newer drugs that are not well known can promote PRL secretion by antagonizing PIF and enhancing PRF or enhancing DA-like effects at the DA receptor level. (iii) Pathological Mainly various diseases that cause HPA dysfunction, including hypothalamic and pituitary diseases such as prolactinoma, GH tumor, ATCH tumor, empty saddle syndrome, pituitary stalk lesions, craniopharyngioma, cerebrospinal radiation, primary hypothyroidism, and some non-endocrine diseases, such as chest wall lesions and spinal cord diseases that are sufficient to cause afferent nerve excitation, chronic renal failure, severe liver disease, etc. The clinical diagnosis of pathological HPL must be made in addition to other causes of PRL elevation. Some patients with menstrual disorders and PRL often >100ug/L, and patients with long duration of disease without obvious clinical symptoms, should be alerted to the possibility of “latent microprolactinomas”, which can be found on follow-up with positive changes in PRL on imaging review. (iv) Idiopathic and Macroprolactinemia Those who do not belong to the above four categories and the cause is not known, among them, after several years of follow-up and without clinical symptoms and imaging evidence may be “idiopathic HPL”; some cases may be “Macroprolactinemia” (Macroprolactinemia). Macroprolactinemia.) There are many forms of PRL in human serum, with a large amount of “little PRL” (little PRL), which has a molecular weight of 23 kDa and is actually a PRL monomer, and a small amount of “big PRL” (big PRL), which has a molecular weight of 50–60 kDa. The molecular weight is 50–60 kDa, while 10-26% of HPL can be “big big PRL” or “big big or macroprolactin” with a molecular weight of 150–170 kDa. Macroprolactin is a high molecular weight “PRL-IgG immune complex” formed by PRL monomers and autoantibodies, whose renal clearance is reduced and which accumulates in the blood to form macroprolactinemia. This complex has no physiological activity of PRL, so it is actually a “pseudohyperprolactinemia”. In clinical practice, this often leads to misdiagnosis and improper management. When PRL levels are elevated and clinical symptoms are absent (or atypical) and macroprolactinemia is suspected, serum PRL levels can be measured in patients before and after polyethanol treatment. Patients did not show other autoimmune manifestations, and autoantibodies such as ANA, TPOab, and TGab were normal, but CD5+ lymphocytes were significantly increased. Japanese scholars used gel affinity chromatography and SDS-PAGE to identify an anti-PRL IgG, which can bind to PRL monomers to form giant PRL. Pathogenesis Pharmacological mechanisms have been described above. The pathogenesis of pathological HPL can be one of the following: (1) Insufficient hypothalamic PIF or blockage of the downward transmission to the pituitary gland, which releases the normal inhibitory regulation of pituitary PRL cells, is seen in hypothalamic or pituitary lesions, often with total hypopituitarism or damage to the pituitary stalk due to trauma or surgery. In primary hypothyroidism TRH (as PRF) can be significantly increased and the inhibition of PRL by DA removed; (ii) Autonomous hypersecretion of monoclonal strains of PRL cells, such as PRL tumors as well as “endocrine with cancer syndrome”, but their secretion is not pulsatile and the normal cycle pattern of sleep-wake cycles, estrogen induction, etc. disappears (iii) afferent nerve enhancement stimulation enhances PIF action, as seen in various types of inflammatory, traumatic and neoplastic diseases of the chest wall, as well as spinal cord lesions; (iv) impaired renal degradation of PRL (seen in renal failure), or pseudoneurotransmitter formation in hepatic encephalopathy, thus diminishing PIF action (seen in severe liver disease). Clinical manifestations (a) Overflow, amenorrhea/hypogonadism and infertility: HPL, regardless of its etiology, can be associated with overflow, amenorrhea (or oligomenorrhea) and infertility in women of childbearing age. According to statistics, about 1/3 of amenorrhea cases are HPL, up to 70% of amenorrhea patients with overflowing breast, 15% of anovulatory women are HPL, and 43% of anovulatory patients with overflowing breast are HPL. High levels of PRL inhibit the production of progesterone by ovarian granulosa cells, and also contribute to a compensatory increase in hypothalamic DA (especially in patients with PRL tumors), which inhibits LRH and LH and suppresses ovulation. Patients with mildly non-persistent high PRL levels (PRL often <100 μg/L) may have normal menstrual cycles but no ovulation due to varying degrees of LRH suppression, or they may have frequent menstruation (often without ovulation and only occasionally with ovulation) due to luteal hypoplasia (short luteal phase). With a significant increase in PRL levels, competition can inhibit the binding of GnH to ovarian GnH receptors resulting in scanty menstruation and amenorrhea. 90% of patients with PRL tumors have breast overflow, bilateral or unilateral, mostly extruded, which can be temporary or intermittent, with a small amount of more spontaneous overflow and white or yellow milk. Overflowing and occlusion are often the main manifestations of the disorder and the reason for female patients to visit the clinic. Overflow needs to be differentiated from nipple discharge from papillomas or carcinomas in the ducts of the breast. In cases of elevated PRL with amenorrhea but no breast discharge, hypopituitarism or chronic E2 deficiency should be considered, as HPL caused by pituitary PRL tumors can itself cause low serum E2 with corresponding symptoms. A small number of patients (5-7%) with PRL tumors may present with primary amenorrhea, increased serum dehydroisosterone, hirsutism, water retention, weight gain, anxiety and depression. Sixty percent of these patients have a decreased or absent libido. In males, serum testosterone may be reduced, sperm count may be reduced or lost, resulting in infertility, libido may be reduced or lost, and erectile dysfunction may be present to varying degrees, which is often overlooked by patients and physicians. 1/3 of male patients may have a small amount of extruded breast milk. In adolescents, puberty may be delayed, and in the case of macroadenomas, growth may be affected. (ii) Osteoporosis in both men and women, HPL can cause progressive decrease in bone density, resulting in osteoporosis, which may improve with normal PRL and sex hormone levels. (iii) A cluster of occupying signs caused by pituitary macroadenoma (see pituitary tumor). (iv) Associated signs and symptoms of the primary disease. Diagnosis (a) History and physical examination: Pay attention to specific symptoms, such as amenorrhea, overflow and infertility in women of childbearing age, hypogonadism, erectile dysfunction and overflow in young and strong men, etc. Detailed information on menstrual history, childbirth history, breastfeeding history, medication history, as well as neurological symptoms (presence of headache, vision and visual field changes) and disease history should be obtained. It is also important to exclude physiological and pharmacological factors, as well as the relationship between other existing diseases and hyperprolactinemia. The physical examination should focus on changes in visual field, visual acuity, mammary glands (whether there is white milk overflow, between colostrum and breast milk, sometimes milk overflow after squeezing, unilateral in a few patients), chest wall, male gonads, etc.). (2) Endocrinological examination (1) Serum PRL measurement and PRL dynamic test Non-prolactinoma-induced HPL, PRL rarely >100μg/L, PRL >100μg/L PRL tumor is very likely, the larger the PRL tumor, the higher the PRL level, >200nμg/L is often a large adenoma (>10mm). Mildly elevated PRL (<60μg/L) may be a stress or pulse secretion peak. To avoid stress, blood can be collected for 3 consecutive days or 3 consecutive times on the same day, each time 1 hour apart, so that the 3 serum measurements can exclude the pulse peak and facilitate judgment. Drugs that stimulate PRL secretion, such as TRH, metoclopramide, chlorpromazine, cimetidine, arginine, or drugs that inhibit PRL secretion, such as levodopa and bromocriptine, can be used selectively to observe the dynamic changes of PRL. PRL tumors do not respond significantly or have diminished responses to the above stimulants and inhibitors, which helps to distinguish idiopathic HPL, GH, ACTH tumors from PRL tumors, but for It can help to distinguish idiopathic HPL, GH, ACTH tumor and PRL tumor, but it has little value for idiopathic HPL (see below). (2) Other endocrine function tests Thyroid function measurement, gonadotropin and E2 and testosterone measurement, GH and ACTH measurement, DHEA measurement, etc. should be performed selectively in different cases to help determine the cause and condition. (c) Imaging MRI or CT to detect hypothalamic or pituitary lesions. See "PRL tumor" and "pituitary tumor" below. Treatment: 1) L-thyroxine replacement therapy for primary hypothyroidism; 2) Discontinuation of medications for heterogenous HPL; 3) Treatment with bromocriptine for HPL with hypogonadism for 1 to 2 years, but imaging does not confirm the diagnosis of pituitary lesion. Inhibit PRL secretion and restore gonadal function; 4. See the relevant section for treatment of pituitary tumors, and see below for treatment of PRL tumors. Patients with pituitary macroadenoma often have hypopituitary hypofunction and require replacement therapy with appropriate hormonal agents.5 Others: female patients with suspected PRL tumors should not be treated with estrogen to prevent PRL tumors from growing; patients with hyperprolactinemia after oral contraceptive use who still have clinical symptoms after discontinuation of the pill may be treated with gonadotropin or chlordiazepoxide to promote complete restoration of the hypothalamic-pituitary-ovarian axis; postpartum lactation with amenorrhea with PRL. For postpartum lactation with amenorrhea and increased PRL, oral contraceptives (according to the dosage of contraception, but should not be taken for a long time to avoid the PRL-releasing effect of oral contraceptives) and vitamin B6 (200-600 mg/d) (the latter is a dopamine decarboxylase coenzyme that converts dopamine into DA in hypothalamic peptidergic neurons) can be used; some HPL patients with PCOS are treated with bromocriptine. Some patients with HPL with PCOS can be treated with clomiphene after the PRL level drops to normal and ovulation can be resumed in about 3-10% of those who still do not ovulate. No treatment is needed for "mega-PRL". Prolactinoma (PRL tumor) is the most common functional pituitary tumor (about half) and the leading cause of pathologic hyper-PRLemia. a NIH study showed that 1/4 of the US population has pituitary microadenomas, 40% of which are PRL tumors. The size of a PRL tumor is related to PRL secretion, and usually the larger the tumor, the higher the PRL level. pituitary tumors with only moderately elevated PRL levels (50-100 ng/ml) may be mixed PRL tumors (see below), with endocrine symptoms different from those of monoclonal PRL tumors. With the widespread use of serum PRL measurements and high-resolution imaging such as CT and MRI, the clinical diagnosis rate of micro-PRL tumors has improved greatly. The pathogenesis of PRL tumors has not yet been fully elucidated. In addition to disorders of PRF and PIF regulation, the functional deficits of PRL-secreting cells and the factors affecting them remain to be clarified. Clinical and animal studies have demonstrated that estrogen promotes PRL cell proliferation and PRL synthesis and secretion. After pregnancy, PRL cells may increase in size, proliferation, pituitary gland enlargement and PRL secretion as estrogen levels rise in normal women. As for oral contraceptive pills (CCP), they have some estrogenic activity and can cause hyper-PRLemia. However, studies have shown that oral contraceptives, especially CCP with low estrogenic activity, are not associated with the occurrence of PRL tumors; in addition, intrinsic defects of PRL tumor cells have been demonstrated: (i) murine PRL tumors and human micro-PRL tumor secretion are resistant to the inhibitory effects of bromocriptine and dopamine; (ii) most PRL tumor patients with repeated DA agonists or antagonists or nonspecific insulin hypoglycemic stimulation after surgery, their This indicates that the autocrine secretion of most patients with PRL tumors originates from an intrinsic defect, and the hypothalamic regulation disorder is secondary; (3) the efficacy of bromocriptine is not related to the size of PRL tumors and the original PRL level, and the efficacy of some patients is unsatisfactory even though the dose is doubled, indicating that these patients are resistant to bromocriptine; (4) the DNA clonal analysis of PRL tumors at the end of last century showed that PRL tumor cells are monoclonal. The DNA clonal analysis of PRL tumors at the end of the last century showed that the PRL tumor cells were monoclonal and the cells around the tumor were normal. PRL can be reduced to normal after tumor excision. PRL tumors can be classified according to size as microadenoma (<10 mm), and macroadenoma (>/=10 mm), with significant differences in biological behavior between the two. The disease is most common in young adults between 20 and 40 years of age, and is significantly more common in women than in men. The majority of PRL tumors are benign and PRL cell carcinoma is rare. [Clinical manifestations] may vary from asymptomatic incidental finding to hypopituitarism, even pituitary stroke and blindness. (i) Overflow of breast and hypogonadism The typical symptoms are amenorrhea, overflow of breast and infertility in women of childbearing age, and hypogonadism, impotence and infertility in men (see “hyperprolactinemia”). (b) Pituitary tumors with occupational symptoms Macroadenomas can produce occupational neurological symptoms and hypopituitarism (see Pituitary tumors). In men with pituitary PRL adenoma, although they have symptoms of hyperprolactinemia, they are often overlooked and not diagnosed in time until the tumor increases in size and the above-mentioned symptoms of tumor compression appear. (Acute pituitary stroke: 0.6-10% of pituitary tumors can bleed spontaneously, usually in macroadenomas, occasionally in microadenomas. The main symptoms are meningeal irritation due to severe hemorrhage and compression of surrounding tissues, mainly visual acuity, visual field damage and headache. Other endocrine symptoms of PRL mixed tumor PRL tumor can be mixed with other pituitary hormone adenoma or occur simultaneously, most commonly GH and PRL mixed tumor, 20%-40% of cases of acromegaly have elevated serum PRL level, and there may be amenorrhea and overflow of breast (mostly extrusion). Bromocriptine treatment will reduce the serum PRL quickly without significant reduction of the tumor. 3. Chronic high PRL levels can promote bone loss, especially in patients with extremely low E2 concentrations, and their BMD is often lower than the average level in menopausal women. 4. Prepubertal PRL tumors Mostly macroadenomas, patients with arrested growth, short stature, breast overflow and primary amenorrhea. (a) Excluding physiological and pharmacological hyperprolactinemia (b) PRL measurement, PRL dynamic test and other endocrine function tests (corresponding endocrine function tests are often required for suspected mixed tumors (see “Hypothalamic-pituitary function tests”) (c) Imaging tests Because of its low resolution and indirect imaging effect, it is no longer routinely used in the diagnosis of PRL tumor. CT and MRI, because of their high resolution and direct imaging effect, can detect micro adenomas of 3-4 mm, especially for follow-up after treatment. However, CT still has certain false-positive and false-negative rates for microadenomas. MRI has become an important method for diagnosing pituitary adenomas because of its high resolution of soft tissues, clear display of anatomical structures, and its ability to reflect the growth of pituitary tumor tissues in all directions, provide comprehensive imaging characteristics of pituitary adenomas, determine whether the cavernous sinus is invaded or not, and is important for the formulation of surgical methods and the prevention and reduction of intraoperative hemorrhage and other complications. It has become a common examination method for the diagnosis of pituitary adenoma. Preoperative MRI can be used to assess the extent and mode of growth of pituitary adenoma and to estimate the texture of the tumor, which can be used as a guide for the development of surgical plan. However, MRI cannot differentiate between bone and calcified tissue, and is less effective than CT in showing tumor encroachment on the saddle wall and extension outside the saddle. The diagnosis of pituitary microadenoma should be distinguished from small cysts in the saddle, as well as physiological pituitary glands with mild enlargement and signal inhomogeneity during menstruation and pregnancy in adolescent women to avoid misdiagnosis. Other common lesions in the saddle, such as intra-saddle arachnoid cysts and Rathke’s cysts, and vacuolated saddle syndrome (patients with normal or slightly elevated prolactin in addition to amenorrhea, often accompanied by headache) also need to be differentiated. [Treatment] For PRL tumors with high PRL secretion and occupying neurological symptoms and hypopituitarism, treatment with DA agonists may be indicated, and surgical resection or radiotherapy may be performed simultaneously or electively to improve clinical symptoms and reduce or even eliminate the tumor for best results. Unlike macroadenomas, 95% of microadenomas do not grow progressively, so inhibition of tumor growth is not an indication for treatment. The two main points of microadenoma treatment are to target infertility and to restore menstruation and eliminate breast discharge. For infertility, bromocriptine should be preferred; for inhibition of macroadenoma growth, the efficacy of various DA agonists does not differ much. Drug therapy (a) DA agonist therapy 1 Bromocriptine is an ergot derivative that acts as a specific DA receptor agonist. The inhibition of PRL secretion by bromocriptine is due to: inhibition of PRL secretion by direct excitation of D-2 receptors in pituitary PRL cells and increase of PIF release by indirect excitation of D-2 receptors in hypothalamus. Bromocriptine specifically inhibits PRL-mRNA and PRL synthesis, leads to cytoplasmic reduction of cell vacuole formation and cell fragmentation and apoptosis, and inhibits PRL tumor growth without damaging other pituitary cells. It can also inhibit overflow of breast milk and restore gonadal function and fertility (80-90% of female patients of reproductive age treated with bromocriptine can restore ovulation); for male patients with PRL macroadenoma, in addition to the reduction of tumor size and suppression of PRL secretion, serum testosterone level and sperm count can be restored to normal. Bromocriptine is rapidly absorbed from the intestine after oral administration, but the absorption is not complete. The half-life is about 3 to 4 hours, so the daily dose is divided into 2 to 3 doses. After a single dose intake, peak plasma levels are reached in 2-3 hours. Bromocriptine is metabolized by the liver, 90% is excreted in the feces and 10% is excreted in the urine. Due to its non-hydrophilic brain concentration is significantly higher than serum concentration. In order to determine the effective dose, a sensitivity test can be conducted at the beginning of the treatment, and the serum PRL level can be decreased by >50% in most patients after taking 2.5mg of bromocriptine, which means that only a smaller dose (3.75-7.5mg/d) can be effective. This dose difference may depend on the pituitary gland. This dose difference may depend on the responsiveness of the pituitary PRL cell DA receptors to the drug. The starting dose may be 0.625 mg/d after dinner, followed by weekly increments of 1.25 mg/d, divided into morning and evening doses. For well-tolerated patients the daily dose is given once for the same efficacy. During drug treatment, PRL was measured every 1 to 2 months and the dose was adjusted promptly during follow-up clinic visits. The effective dose (restoration of menstruation and PRL levels) is usually 5.0 to 7.5 mg/d, and up to 7.5 to 10 mg/d for macroadenomas. 80% of macroadenomas shrink after treatment, either as early as 4 to 6 weeks after treatment, or after several months. After 24 months or more of treatment, 25% of patients can remain normal after discontinuation of the drug. Macroadenomas may calcify significantly after long-term drug treatment. Bromocriptine treatment normalizes PRL in 82% of patients and restores menstruation and fertility in 90% of patients. Therefore, bromocriptine is the drug of choice for patients who need to restore ovulatory function. Patients with microadenoma who wish to become pregnant must use mechanical contraception during treatment until their second regular ovulatory period, after which they must stop taking bromocriptine once they have had their period and continue to stop taking it if pregnancy is confirmed. This will prevent bromocriptine related miscarriages, ectopic pregnancies and infant genital malformations. Bromocriptine should be continued during breastfeeding and reviewed after a certain period of breastfeeding if necessary. 31% of patients with macroadenoma have an increase in the size of the tumor during pregnancy, but less than 2% of microadenomas have an increase in the size of the tumor. Therefore, macroadenomas need to be operated before pregnancy and bromocriptine should be taken after surgery and even during pregnancy to prevent the growth of the tumor. For male patients, different options are available depending on the presence or absence of symptoms, and asymptomatic microadenomas can be left untreated and followed up regularly. Bromocriptine is preferred for the treatment of pituitary PRL microadenomas or macroadenomas without suprasellar development or visual field defects because of its efficacy, low complications and better recovery of pituitary function. The adverse effects of bromocriptine are related to its activity on D-1 and D-3 receptors, adrenergic receptors and serotonin receptors, and are commonly associated with irritation of the gastrointestinal mucosa, nausea, vomiting and abdominal pain. Higher doses may cause dizziness, headache, drowsiness, constipation, upright hypotension, nasal congestion and other reactions due to relaxation of visceral smooth muscle and inhibition of sympathetic nerve activity. Occasionally, serious adverse reactions may occur in high dose treatment and require caution. The side effects of small doses of bromocriptine are often transient and can often be alleviated by taking it after meals. Therefore, the drug should be started in small doses and increased slowly to avoid these side effects. This is related to the heterogeneity of DA receptors in PRL tumors and not to PRL levels or tumor size. Patients with adenomas resistant to bromocriptine can try the following two drugs that have a higher affinity for D2 receptors. Cabergoline, a long-acting ergot derivative, is a highly selective agonist for the D-2 receptor in PRL-secreting cells and is therefore better tolerated than bromocriptine. It can reduce PRL levels, restore sexual function and shrink tumors. It can be administered 1-2 times a week (0.5 mg) because of its long half-life of 62-115 h. As it is a first-line drug for PRL tumors, it can be used for those who are intolerant or resistant to bromocriptine. It must be used with caution in patients with severe cardiovascular disease, Raynaud’s disease, ulcer disease, hypotension, etc. The association of cabergoline with pathological gambling has been reported but is rare. In contrast to bromocriptine, which can reduce the size of macroadenomas by 1/2 in only 2/3 of patients, cabergoline can have the same effect in 80-90% of macroadenomas and improve the visual field in 90% of patients. After more than 2 years of cabergoline treatment, PRL levels remain normal and the tumor does not increase in size in 2/3 of patients after stopping the drug. 3. Quinagolide (Quinagolide), trade names such as “Norprolac” (Norprolac). This is a new non-ergot long-acting non-specific DA agonist, can excite D2 receptors, but also act on D1 receptors and other neurotransmitter system. Its structure is octahydrobenzylquinoline, and its inhibitory effect on PRL is 35 times higher than that of bromocriptine, while the digestive side effects are less. Doses of 75-400 μg/d (maintenance 75-150 μg) can bring PRL control to normal in 3/4 of patients with macroadenomas (about half of the patients have PRL reduction to normal within 3 months, while some patients need 12 months), and more than half of the patients have adenomas that shrink by more than 25%. This class of drugs is also the second line of treatment for PRL tumors and is often used for those who are resistant or intolerant to bromocriptine. The start of treatment may cause upright hypotension due to dopamine excitation, and most patients may experience the following side effects: nausea, vomiting, or headache, dizziness, or fatigue, most of which are seen at the beginning of treatment and may resolve on their own. Therefore, the starting dose should be selected according to the effect of PRL reduction and the patient’s tolerability. It should be used with caution in patients with a history of psychiatric disorders. (ii) PPARγ (peroxisome proliferator-activated receptor γ) can be expressed in all pituitary tumor cells, and studies have confirmed that its ligand, rosiglitazone, can inhibit the proliferation of pituitary tumor cells and promote their apoptosis by preventing quiescent cells from entering G0 into G1 phase, reducing the number of cells entering S phase, and inhibiting the secretion of tumor cell hormones. It was also found that rosiglitazone significantly inhibited the growth of pituitary PRL tumors in mice. Rosiglitazone has been widely used clinically as a highly selective PPARγ agonist for insulin resistance, and its inhibition of PRL tumors has the potential to be a new option for the treatment of PRL tumors, which is still in the research stage. Surgery Surgery may be an option for macroadenomas that are insensitive to drug therapy (insignificant shrinkage of the tumor and decrease in PRL) or for those who cannot adhere to drug therapy (e.g., considering pregnancy and other factors). Those with existing suprasellar involvement may be treated with both medication and surgery. In addition to the traditional transfrontal pituitary tumor major excision for cross-optic decompression (for macroadenoma with supra- or paramedian extension with cross-optic or other cerebral nerve compression), the less invasive transsphenoidal selective pituitary tumor resection is now more frequently performed, which is suitable for microadenoma and also for cases with less severe cross-optic compression with supra-addle extension. If residual tumors are present after surgery, continued pharmacological treatment or supplemental radiation therapy is required. Complications such as infection, cerebrospinal fluid leakage and transient uveitis can occur after surgical procedures. The long-term follow-up recurrence rate is 20% for both, and the mortality rate is 0%-1%. Radiation therapy is often used when PRL levels do not fall to normal after surgery and when there is residual tumor tissue. Radiation therapy can also be given to patients who are pregnant with medications to inhibit the progression of pituitary tumors during pregnancy and to reduce the dose of medications used in the long term. Radiation therapy alone or with adjuvant surgery, conventional radiotherapy has been abandoned because of its delayed efficacy, its tendency to cause secondary pituitary hypoplasia (especially the incidence of pituitary gonadotropin LH and FSH deficiency of 47% and 70%, respectively), and its potential tendency to damage visual field, vision and hypothalamus. Nowadays, stereotactic radiotherapy, such as γ-knife or X-knife, is mostly used, with the advantages of accurate localization and short course for hypothalamic and cranial damage, but there are still long term complications. It is often used for microadenoma with clear periphery and without invasion of adjacent structures, and those who cannot tolerate long-term drug treatment, as well as those who have residual tumor tissue from surgery or recurrence and are not suitable for re-operation, or those who are too old or have miscellaneous diseases to undergo surgery can consider γ-knife treatment as adjuvant therapy.