Hyperprolactinemia

The increase of prolactin is not necessarily a prolactinoma. There are many reasons for the increase of prolactin, including staying up late, drugs, fasting, tension during blood drawing, etc. Of course, other types of pituitary macroadenomas or other tumor lesions in the sellar region compress the pituitary stalk, which will also lead to the increase of prolactin. Experienced doctors will identify the factors that lead to the increase of prolactin through the medical history inquiry, and then carefully read the imaging film to finally determine whether it is prolactinoma. Physical examination, pregnancy preparation or medical treatment due to menstrual disorder may find that prolactin is increased. If the prolactin test result is less than 200ng/ml (or the upper limit of the normal range of prolactin is less than 10 times), it is recommended to retest prolactin instead of immediately doing MRI. During retest, it is required not to stay up late the day before blood drawing, not to be empty before blood drawing, and to sit still for 5-10 minutes before blood drawing. If prolactin is significantly increased twice or more, and there are symptoms such as amenorrhea, galactorrhea, hypolibido, sparse body hair, etc., pituitary enhanced magnetic resonance examination is required; If the initial prolactin test result is greater than 200ng/ml, and drug factors are excluded, it is recommended to do pituitary enhanced magnetic resonance examination. When more than 60% of the prolactin in the blood is composed of macroprolactin, this disease is also called macroprolactinemia. The latest research results show that macroprolactin blood is a kind of inactive isomer of prolactin, which is a normal physiological phenomenon and will not affect the human body, but will interfere with the detection of prolactin. When the concentration of macroprolactin is too high, it may lead to the wrong diagnosis of hyperprolactinemia, thus causing unnecessary examination and/or drug treatment. According to statistics, the incidence of macroprolactinemia in global patients with hyperprolactinemia is 18.9%. Therefore, early screening of macroprolactin blood is helpful to avoid misdiagnosis and unnecessary treatment. Therefore, when the symptoms and imaging diagnosis are inconsistent with the results of hyperprolactin, macroprolactin examination is recommended. The giant prolactin test project declared by the multidisciplinary clinical diagnosis and treatment team composed of the Laboratory Medicine Department, Endocrinology Department and Neurosurgery Department of Huashan Hospital won the "UNIVATS Excellence Medical Award", becoming the only Chinese team to win the award in 2024. The abnormal increase of prolactin excluding tumor factors does not necessarily require medication in the following cases: prolactin is slightly increased, but there are no symptoms related to hyperprolactinemia, such as amenorrhea, galactorrhea, decreased libido, decreased body hair, and decreased sperm quality. It is recommended to recheck prolactin every 3-6 months, and recheck pituitary enhanced MRI one year later. Fortunately, compared with other functional pituitary adenomas, patients with prolactinoma can choose drug treatment first. Therefore, the previous treatment is mostly drug therapy. However, drug therapy also has its limitations, such as long-term drug use in young patients, drug sensitivity and delayed drug resistance, sudden tumor stroke during pregnancy in patients with large adenomas and other problems. With the increasingly mature development of endoscopic transnasal surgery technology, the problem of negative effects of drugs is becoming more and more obvious, and many patients with prolactinoma are more willing to accept surgical treatment. Experienced doctors at home and abroad generally believe that pituitary prolactin microadenoma or large adenoma with clear boundary and no invasion of the cavernous sinus can be operated. The clinical research data of the Golden Pituitary Team of Huashan Hospital shows that the total removal rate of microadenoma surgery is as high as 90%~95%, and the total removal rate of non-invasive large adenoma surgery without taking drugs before surgery is also close to 90%. Therefore, surgery can be the first choice for prolactinoma patients with high total resection rate and young fertility needs. Pituitary tumor apoplexy (sharp visual loss, accompanied by severe headache, nausea and vomiting), pituitary macroadenoma with hemorrhage and cystic change (drugs can not shrink the part of hemorrhage and cystic change), tumor with cerebrospinal fluid rhinorrhea or cerebrospinal fluid rhinorrhea after taking drugs, cerebrospinal fluid rhinorrhea repair should be performed as soon as possible. If the effect of drugs and radiotherapy for invasive giant prolactinoma is poor and the tumor continues to grow, surgery should also be considered. In general, experienced pituitary tumor surgeons have carefully evaluated the safety of surgery when deciding on treatment plans and recommending surgery. Although from the perspective of scientific theory and current surgical development, pituitary hypofunction, cerebrospinal fluid rhinorrhea, intracranial infection, bleeding, vision loss, olfaction loss or anosmia, sinusitis, etc. are still inevitable after surgery (the incidence of some serious complications is actually very low), when pituitary tumor surgeons give surgical treatment suggestions, It should be that the advantages of surgery outweigh the disadvantages. At present, bromocriptine can only be obtained from hospitals in China. It is initially taken in small doses (it is not recommended to take it on an empty stomach), and gradually increased to a dose matching prolactin and tumor size to minimize the side effects of the drug (nausea and vomiting, dizziness, constipation, nasal congestion, etc.). However, few patients have serious side effects or can hardly tolerate these discomfort. The psychological disorders (depression and anxiety) caused by long-term drug treatment have also attracted the attention of many clinicians. The efficacy and side effects of cabergoline abroad are significantly better than bromocriptine, but the difficulties in obtaining drugs, the limited efficacy for completely drug-resistant prolactinoma, and the heart valve risk (low incidence) of the drug are all problems that clinicians will mention. In addition, the problem of tumor fibrosis caused by drugs (increasing the difficulty of surgery) and long-term medication will also perplex some patients who are not prepared for long-term medication. Male prolactinoma is mostly different from female patients. The prolactinoma is very high, and the tumor is huge and aggressive, which brings great challenges to clinicians. Therefore, male prolactinoma is classified as one of the five most refractory pituitary tumors. In most cases, male invasive prolactinoma is the first choice to take medicine. Some patients have good drug treatment effect, and the tumor is significantly reduced. However, a small number of male patients with prolactinoma take large doses of drugs. Although the tumor shrinks, the prolactin is still very high. For young men who have fertility needs, it will undoubtedly affect the quality of sexual life, and the decline in sperm quality will increase fertility difficulties. Therefore, Huashan Golden Pituitary Team proposed that for invasive prolactinomas with controllable surgical risk and more than 90% tumor resection, tumor reduction surgery can be performed, and drug treatment can be continued after surgery (conducive to satisfactory control of prolactin by drugs, or residual tumor and prolactin can be controlled by small doses of drugs), which can also avoid considering surgical treatment due to poor drug treatment effect, Trapped in the embarrassing situation that drugs cause tumor fibrosis and increase the risk of surgery. The above suggestions come from my experience in the treatment of pituitary adenomas in the past 30 years, combined with a large number of literature and expert consensus, hoping to help patients with hyperprolactinemia or pituitary prolactinoma. However, every specialist doctor has experience and understanding limitations. If the doctor is still unable to satisfactorily explain your condition and provide appropriate treatment, please consult more domestic experts in relevant fields, or you can log on to the outpatient service public account of Huashan Hospital via WeChat, click multidisciplinary joint outpatient service, and make an appointment for pituitary MDT Outpatient, I believe that the consultation and discussion of multidisciplinary experts will give you a satisfactory diagnosis and treatment plan.

1、 Definition of hyperprolactinemia Hyperprolactinemia refers to the abnormal increase of serum prolactin (PRL) level caused by various reasons. Generally, the serum PRL level of women of childbearing age is generally lower than 30ng/mL, while the serum PRL level of patients with hyperprolactinemia exceeds 25ng/mL. According to the serum prolactin level, hyperprolactinemia can be divided into mild (25-50ng/mL), moderate (50-100ng/mL) and severe (>100ng/mL). 2、 The causes of hyperprolactinemia are complex and diverse. The causes of hyperprolactinemia mainly include the following categories: physiological factors: pregnancy, lactation, stress state (such as emotional tension, cold, anesthesia, surgery, hypoglycemia, etc.), meals, etc. can lead to a transient increase in prolactin. Pharmacological factors: Some drugs such as phenothiazines, risperidone, and oral contraceptives can cause hyperprolactinemia by antagonizing hypothalamic dopamine or enhancing prolactin releasing factor (PRF) stimulation. Pathological factors: hypothalamic diseases: craniopharyngioma, glioma, sarcoidosis, etc. oppress the pituitary stalk. Pituitary diseases: prolactin type pituitary microadenoma, pituitary growth promoting hormone adenoma, etc. Systemic diseases: primary hypothyroidism, chronic renal failure, severe liver disease, etc. Neurogenic factors: chest wall lesions, herpes zoster neuritis, breast surgery, etc. Others: polycystic ovary syndrome. Idiopathic: The serum prolactin of some patients slightly increased, but the pituitary, central nervous system and system examinations were negative, which may be related to the presence of abnormal structure of prolactin molecules. 3、 Symptoms of hyperprolactinemia The symptoms of hyperprolactinemia are mainly related to the impact of the increased level of prolactin on the endocrine system. Common symptoms include: lactation: about 2/3 of patients will experience lactation during non pregnancy and non lactation, and male patients can also experience breast development and lactation. Menstrual disorders and amenorrhea: More than 85% of patients will have menstrual disorders, which are characterized by less menstruation, infrequent menstruation, anovulatory menstruation, etc. The incidence of amenorrhea increases with the increase of blood prolactin value. Infertility: hyperprolactinemia can lead to infertility by inhibiting ovulation, affecting endometrial development and reducing embryo implantation rate. Other symptoms: female may have genital atrophy, decreased libido, bone loss leading to osteoporosis, hirsutism, etc; Men may have decreased libido, erectile dysfunction, decreased sperm count, or even azoospermia. In addition, some patients may also have headaches, dizziness, visual impairment and other symptoms. 4、 Diagnosis of hyperprolactinemia The diagnosis of hyperprolactinemia requires comprehensive information such as medical history collection, physical examination, hormone level determination and imaging examination to exclude physiological and pharmaceutical factors, and to determine the source of hyperprolactinemia and whether there are pathological reasons. Collection of medical history: ask the patient in detail about her menstrual history, lactation, delivery and lactation history, surgical history, past medical history and whether she has taken relevant drugs. Physical examination: check the breast lactation, pay attention to whether there is visual acuity, visual field change, and whether there is hirsutism, obesity, hypertension, chest wall lesions, etc. Hormone level measurement: detect the serum prolactin level, combined with other related hormone level changes, to help clarify the cause. Imaging examination: such as pituitary MRI, which is helpful to find pituitary microadenoma and other diseases. 5、 Treatment plan of hyperprolactinemia The treatment goal of hyperprolactinemia is to inhibit prolactin secretion, restore normal menstruation, ovulation or pregnancy, reduce milk secretion and improve visual impairment. Treatment schemes mainly include the following: drug treatment dopamine receptor agonist: it is the main drug for treating hyperprolactinemia, such as bromocriptine, carmelergoline, etc. Bromocriptine is the most effective drug for treating hyperprolactinemia clinically, but some patients may have adverse reactions such as nausea, dizziness, constipation, etc; The gastrointestinal adverse reactions of cabergoline were mild and well tolerated. Prolactin could be relatively stable in the normal range for a long time after drug withdrawal. Other drugs: Quigolide can be used for those who are resistant to bromocriptine or allergic to ergot. In addition, for patients with fertility requirements, ovulation promoting drugs can also be used as an assistant; For patients with low estrogen status, hormone replacement therapy can be given. Surgical treatment: For patients with drug therapy ineffectiveness or compression symptoms caused by pituitary macroadenoma, surgical resection of pituitary adenoma can be considered. Transsphenoidal microsurgery is a commonly used surgical method, but there are certain risks in the operation, such as easily causing cerebrospinal fluid nasal fistula, and possibly secondary pituitary dysfunction. Other treatments: Proton knife, X-knife and other radiotherapy methods have become effective treatment options for prolactinoma. Lifestyle adjustment: keep healthy living habits, such as proper exercise, keep a good attitude, and avoid overwork, which will help alleviate symptoms. 6、 Precautions for patients with hyperprolactinemia: regular physical examination is required to monitor the prolactin level so as to adjust the treatment plan in time. Avoid incentives: pay attention to avoid physiological incentives that may lead to the increase of prolactin, such as excessive stress, long-term hunger, etc. Medication according to the doctor's advice: patients who take medication should strictly follow the doctor's advice and should not increase or decrease the dosage or stop taking medication. Psychological support: The treatment of hyperprolactinemia may take a long time, and patients need to maintain a positive and optimistic attitude, and can seek psychological support if necessary. Hyperprolactinemia is a common endocrine disease. Most patients can obtain a good prognosis by clarifying the cause and selecting a reasonable treatment plan. Patients need to actively cooperate with doctors in the treatment process, take regular re examinations, and maintain a healthy lifestyle to promote physical recovery and improve the quality of life.

A high level of prolactin does not always mean a pituitary adenoma. Prolactin is a hormone secreted by the anterior pituitary gland, whose main function is to promote the development of mammary gland and the secretion of milk. When the prolactin level rises abnormally, this condition is called hyperprolactinemia, and its causes may include a variety of physiological and pathological factors.

High prolactin is not necessarily a pituitary tumor. There are many factors that cause prolactin increase, and pituitary tumor is only one of them. Reasons for high prolactin: 1. Physiological factors: mental stress, exercise, eating and other stress conditions may lead to high physiological prolactin. 2. Drug factors: Taking anti anxiety and antipsychotic drugs, as well as antiemetics, estrogen drugs, contraceptives, etc., may lead to high prolactin. 3. Tumors: Tumors in the intracranial sellar region, such as craniopharyngioma, hamartoma, vacuolar sella, etc., may also cause high prolactin. 4. Idiopathic increase: prolactin is high due to imbalance of prolactin, prolactin or hormone inhibiting prolactin secreted by hypothalamic pituitary.

Psychotropic drugs involving dopamine must consider the problem of high prolactin, but not limited to antipsychotics. It is very necessary to routinely check this item after medication. If hyperprolactinemia is found with treatment, the first step is to check the pituitary magnetic resonance imaging, especially for the elevation above 100 units. We can't just consider the dopamine blocking effect of drugs in the funnel area It would be safer to come back after empty sella syndrome to consider drug causes. Specifically, when considering the drugs, we should not only consider the dopamine blocking effect, but also consider the high TSH and antihistamine effects of drugs that lead to polycystic ovary and hypothyroidism, which are also the causes of hyperprolactinemia in psychotropic drugs.

The medical project declared by the multi-disciplinary clinical diagnosis and treatment team composed of the Laboratory Medicine Department, Endocrinology Department and Neurosurgery Department of Huashan Hospital: to establish a prolactin monomer detection method and specific reference interval to enhance the ability to identify macroprolactinemia, which stands out from many medical institutions around the world and won the "UNIVATS" award Outstanding Medical Award ", becoming the only Chinese team to win the award in 2024. The "UNIVATS Excellence Award" was jointly selected and awarded by seven leading global healthcare organizations (IFCC, ADLM, EHMC, Modern Healthcare, HIMSS, NAHQ, IHE). The jury selected the excellent project team to achieve quantifiable performance improvement from five aspects of uniqueness, accessibility, scalability, standardized processes and laboratory intelligence. So far, the award has attracted more than 175 countries and hundreds of projects every year. Previously, the prolactin monomer detection project has won many honors, including the third prize of the 10th Shanghai medical staff scientific and technological innovation "Starlight Plan" in 2020, the second prize of the first National Endocrine Disease Test and Clinical Thinking Case Competition in 2021, and the silver prize of the 34th Shanghai Excellent Invention Selection Competition in 2022. Hyperprolactinemia is a common clinical disease caused by many reasons, and the serum prolactin level is continuously higher than the normal range. Although hyperprolactinemia will not endanger life, it will lead to serious complications, including irregular menstruation, infertility, decreased libido, breast hyperplasia, milk secretion and other problems. Hyperprolactinemia may also lead to male infertility, decreased libido, breast enlargement and other problems. Therefore, timely identification and treatment of hyperprolactinemia is crucial to improve the quality of life of patients. When more than 60% of prolactin in the peripheral blood circulation is composed of macroprolactin, this disease is also called macroprolactinemia. The latest meta-analysis results show that macroprolactin blood is an inactive isomer of prolactin, which will interfere with the immunoassay for prolactin detection. If the concentration of macroprolactin is too high, that is, when more than 60% of circulating prolactin is composed of macroprolactin blood, it may lead to the wrong diagnosis of hyperprolactinemia, which may result in unnecessary examination and/or drug treatment. According to statistics, among the global hyperprolactinemia, the incidence of macroprolactinemia is 18.9% (95% CI 15.8%, 22.1%). Therefore, early screening of macroprolactin blood is helpful to avoid misdiagnosis and unnecessary treatment. The Laboratory Medicine Department of Huashan Hospital cooperated with the Endocrinology Department and the neurosurgery "Golden Pituitary" multidisciplinary, through case discussion, understanding of clinical needs, establishing a giant prolactin blood screening plan, especially adopting the standardized laboratory operating procedures of polyethylene glycol precipitation, and building a prolactin monomer detection method based on the chemiluminescence immune detection, The reference interval of prolactin monomer was established, which was verified by clinical samples and confirmed that the method could be used to identify macroprolactinemia. The prolactin monomer detection method and the use of gender specific reference intervals established by the team can help clinicians diagnose hyperprolactinemia and pituitary tumors more accurately, and avoid unnecessary drug treatment. Zhao Yao, chief physician of neurosurgery department of Huashan Hospital, said that prolactin monomer detection can greatly alleviate the anxiety of patients and their families. Compared with the original method based on imaging, prolactin monomer detection can help clinicians to make a clear diagnosis six months earlier. Ye Hongying, chief physician of the Endocrinology Department of Huashan Hospital, said that prolactin monomer detection has the role of making a clear diagnosis and shortening the course of treatment in the diagnosis and treatment of hyperprolactinemia, which can significantly shorten the treatment process of patients and reduce the cost of patient care. The multidisciplinary clinical diagnosis and treatment team of Huashan Hospital affiliated to Fudan University starts from subtlety and creates outstanding clinical value with innovative thinking. The giant prolactin screening project is a model of collaboration between different disciplines to solve clinical and patient needs, and has fully implemented the concept of taking disease as the chain and patients as the center. (Transferred from the subscription number of Huashan Hospital Affiliated to Fudan University, Department of Laboratory Medicine)

High prolactin is not necessarily a pituitary tumor. There are many factors that cause prolactin increase, and pituitary tumor is only one of them. Reasons for high prolactin: 1. Physiological factors: mental stress, exercise, eating and other stress conditions may lead to high physiological prolactin. 2. Drug factors: Taking anti anxiety and antipsychotic drugs, as well as antiemetics, estrogen drugs, contraceptives, etc., may lead to high prolactin. 3. Tumors: Tumors in the intracranial sellar region, such as craniopharyngioma, hamartoma, vacuolar sella, etc., may also cause high prolactin. 4. Idiopathic increase: prolactin is high due to imbalance of prolactin, prolactin or hormone inhibiting prolactin secreted by hypothalamic pituitary.

How to manage hyperprolactinemia (prolactinoma) during pregnancy? Prolactin (PRL) is an anterior pituitary hormone, whose main function is to induce and maintain breast milk secretion. The serum prolactin level of women of normal childbearing age is generally<25ng/ml. Hyperprolactinemia is an increase in serum prolactin caused by various factors, mainly manifested as amenorrhea, galactorrhea, rare menstruation, infertility and tumor compression symptoms, which is an important cause of female fertility disorders. The pregnant period of women with hyperprolactinemia is dominated by drug therapy, dynamic monitoring and evaluation, multidisciplinary cooperation, and refined and individualized comprehensive management to obtain a good pregnancy outcome. Hyperprolactinemia is defined as the state in which the PRL level in peripheral blood continuously increases due to various reasons, which is called hyperprolactinemia. According to the serum prolactin level, hyperprolactinemia can be divided into the following categories: ≮ mild 25~50ng/ml;  Moderate 50~100ng/ml;  Severe degree ＞ 100ng/ml. Hyperprolactinemia tends to occur in women aged 20-50 years, with an incidence rate of about 1/10000. The peak incidence is around 30 years old, and 40% of hyperprolactinemia is idiopathic. The etiology of hyperprolactinemia hyperprolactinemia is caused by a variety of physiological, pharmaceutical and pathological reasons.  The biological factors include: pregnancy, lactation, stress, exercise, etc; ▄ Drug factors mainly include drugs that antagonize hypothalamic dopamine or enhance the stimulation of prolactin releasing factor and cause hyperpRLemia, such as phenothiazine, methyldopa, morphine, cocaine, estrogen, oral contraceptives, isoniazid, etc;  Pathogenic factors mainly include hypothalamic or adjacent lesions and pituitary diseases, primary hypothyroidism, chronic renal insufficiency, cirrhosis, chest wall diseases, and chronic stimulation of the breast. 20%~30% of hyperpRLemia have pituitary adenoma, the most common is prolactinoma. Pituitary prolactinoma accounts for 30%~50% of all pituitary neuroendocrine tumors. Treatment of hyperprolactinemia High level PRL causes ovulation disorder and luteal insufficiency by inhibiting GnRH pulse, thus causing fertility disorder. The incidence of hyperprolactinemia in infertile women ranges from 9% to 17%, and the incidence of recurrent abortion is 2% to 5%. Therefore, the treatment principle for hyperprolactinemia with fertility requirements is to aim at the cause, restore the PRL level to normal, reduce the size of pituitary tumor, restore normal menstruation and ovulation, reduce complications and prevent recurrence. Drug therapy is the first choice for treatment. Dopamine receptor agonists (DAs) are the main treatment for almost all pituitary prolactinomas, including microadenomas, macroadenomas or giant adenomas. DAs, such as bromocriptine, cabergoline, and quingolide, have therapeutic effects related to individual sensitivity, which can effectively inhibit PRL secretion and reduce tumor size; Long acting DA (cabergoline) is also commonly used in clinical treatment. Small doses are administered at intervals (0.25~0.5mg, once a week), with mild side effects and high compliance, but the price is expensive. After 2 years or more of DAs treatment, if the PRL is normal and the pituitary tumor disappears, the dosage should be reduced or the drug should be stopped. The indications for surgical treatment include drug resistance or intolerance to DAs, or large doses of DAs cannot reduce PRL or tumor volume, or pituitary apoplexy occurs. If patients with mild PRL elevation have regular menstruation and ovulation, there may be macromolecular PRL. Regular reexamination is not necessary. PRL is slightly elevated and accompanied with clinical symptoms. Active treatment should be taken to restore PRL to normal level. The blood PRL of drug-induced hyperprolactinemia was rechecked 3 days after drug withdrawal. If there was no significant increase, no treatment was generally needed. Pretreatment of pregnancy with hyperprolactinemia Pregnancy timing After treatment of hyperprolactinemia, the serum PRL maintained at a normal level for 10 to 12 months, which was conducive to improving infertility. In patients with pituitary microadenoma before pregnancy, the PRL level drops to normal, and pregnancy can be achieved after regular menstruation. For women with large adenomas who have a birth plan, they need to be treated with bromocriptine to shrink the adenomas before pregnancy; For huge PRL tumor, tumor reduction surgery can be considered to relieve the compression symptoms of the tumor and retain the pituitary function. For patients with extrasellar tumors, pregnancy can be achieved only after the tumor shrinks to the boundary of the sellar region. If ovulation still fails to resume after PRL returns to normal, DAs can be combined with ovulation induction therapy. DAs can reduce the level of luteinizing hormone (LH), increase the sensitivity of the ovary to drugs, and increase the pregnancy rate; If the ovarian reserve function is poor or the hypothalamic pituitary function is low, exogenous hormones can be used to assist fertility. During pregnancy preparation, DAs bind to D2 receptors in the anterior pituitary to reduce the proliferation of PRL cells, thereby reducing the synthesis of PRL and reducing tumor volume. The visual field defect was mostly improved within 2 weeks, and the tumor volume was significantly reduced after 3-6 months. Although bromocriptine and cabergoline are both Class B drugs of the US Food and Drug Administration, bromocriptine has a shorter half-life than cabergoline, and bromocriptine has a higher safety. Therefore, bromocriptine is the first choice for patients with fertility requirements. Quigolide is not safe, so it is not recommended for female patients who are preparing for childbirth. The common side effects of DAs include nausea, headache, somnolence and postural hypotension. Therefore, the drug should be administered from a small dose, gradually increased, and maintained at the lowest effective dose. The initial dose is 1.25 mg/d, taken with meals, increased to 2.5 mg/d after one week, and increased to 1.25 mg/d every week until menstruation and ovulation resume. The effective dose is usually 5~7.5 mg/d. During the gradual dose process, attention should be paid to monitoring side effects, and the drug should be stopped as soon as possible after confirming pregnancy. If pregnancy is unexpected during the medication, it is not recommended to terminate pregnancy due to medication. Patients with pituitary microadenoma before pregnancy should stop taking the drug after 12 weeks of pregnancy because of the need to maintain luteal function; In patients with large adenomas before pregnancy, pituitary magnetic resonance imaging (MRI) examination showed that the tumor size was reduced, which could be reduced by 1.25mg/d every 1 to 2 months, and the lowest effective dose was used to maintain the normal level of PRL. It was recommended to use drugs throughout pregnancy. Pituitary adenoma will recur after drug withdrawal. After DAs2 is used for more than two years, the recurrence rate after drug withdrawal is significantly lower than that of patients with short-term application. One year after drug withdrawal is a high-risk time for recurrence. After drug withdrawal, the PRL level is monitored monthly. After three months, the PRL level is reviewed every six months, and then every year. In case of recurrence, the lowest effective dose should be maintained. The indications of surgery or radiotherapy before pregnancy can be considered for those who cannot tolerate drug treatment, have poor drug treatment effect (PRL is normal but the tumor does not shrink), and have giant adenoma with compression symptoms (severe headache and visual field defect). In most cases, transsphenoidal surgery will not damage the gonadal axis, and the surgical effect depends on the skill and experience of the surgeon; Radiotherapy is only used for patients who have failed surgery or considered malignant tumors. After treatment, 30% of the patients' PRL can return to the normal level, but the treatment cycle is long and may be accompanied by hypopituitarism. Evaluation and management of pregnancy The monitoring of blood PRL level during pregnancy is not recommended for routine monitoring during pregnancy. The increase of estrogen level during pregnancy in healthy women leads to the proliferation of pituitary prolactinoma. The PRL level starts to increase in 5-8 weeks of pregnancy, which is related to the increase of the size and number of PRL cells. The response of PRL to normal stimuli (such as sleep, diet, and lactation) remains unchanged throughout pregnancy. Therefore, PRL is not a monitoring indicator of the progress of pituitary prolactinoma during pregnancy. Women with macromolecular hyperprolactinemia (bioactive macromolecules) will produce normal amounts of bioactive prolactin during pregnancy and lactation. MRI examination during pregnancy is not recommended for routine examination during pregnancy, but the evaluation of clinical symptoms should be emphasized. Microadenoma patients have less tumor growth after pregnancy, while large adenoma patients have more than 25% probability of tumor growth after pregnancy. Patients with pituitary microadenoma and macroadenoma were evaluated every 3 months during pregnancy, excluding the monitoring of serum PRL level; For patients with large adenomas without surgical treatment, the number of prenatal examinations and visual examinations can be increased. In case of tumor compression symptoms such as headache or visual field defect, gadolinium free MRI examination and neurology and ophthalmology evaluation are required. The drug maintenance treatment for patients with giant adenoma should be decided by the clinician. There are relatively more reports of bromocriptine continued to be used during pregnancy than other DAs, and there is no clear adverse drug reaction report. Carmergoline can be used for patients who cannot tolerate bromocriptine. It is recommended to conduct clinical evaluation and visual evaluation every 3 months during the medication period. If compression symptoms occur, MRI scanning without gadolinium should be selected; If MRI examination results indicate tumor growth related to clinical manifestations, drug treatment needs to be reassessed, and the symptoms of pituitary tumor growth still cannot be controlled by readjusting the use of DAs. If the drug treatment effect is poor, surgical treatment is preferred in the middle of pregnancy. If it is nearly term, termination of pregnancy can be considered. The basic principle of medication in pregnancy is to limit the exposure of the fetus to drugs in as little time as possible. DAs have no inhibitory effect on placental PRL. In 6272 pregnancies using bromocriptine or 1061 pregnancies using cabergoline, the maternal and fetal outcomes were not significantly abnormal. Although bromocriptine and cabergoline have been proved to have no adverse effects on the pregnancy process or the fetus, they should be stopped in principle if pregnancy occurs during drug treatment; If the pregnant woman has a history of taking DAs, it is not recommended to terminate the pregnancy. Since withdrawal of drugs during pregnancy may lead to tumor growth, clinical symptoms such as headache, visual field defect and diabetes insipidus should be carefully monitored. Postpartum treatment has been observed that postpartum serum PRL level may be lower than that before pregnancy. In some patients, hyperprolactinemia can heal itself after delivery. There is no evidence to support that breast-feeding will stimulate tumor growth. For women who are willing to breast feed, unless the tumor growth induced by pregnancy needs treatment, they will generally review the PRL level after finishing breast-feeding before starting to use DAs. Because DAs inhibit lactation, women who need medication and plan to breastfeed can have MRI reexamination to assess the tumor 4-6 weeks after delivery to weigh the advantages and disadvantages. With the development of monitoring and diagnosis and treatment methods, more and more women with hyperprolactinemia are facing fertility problems. We should pay attention to the reasonable monitoring of the perinatal period and in-depth research on the impact of DAs drug treatment on pregnancy. For women suffering from pituitary adenoma, the perinatal period should be jointly managed by obstetricians and neurosurgeons to minimize complications, so as to obtain a good pregnancy outcome. Source MediEndo Weekly News