Consensus on the diagnosis and treatment of hyperprolactinemia

Hyperprolactinemia refers to a syndrome caused by internal and external environmental factors, characterized by elevated prolactin (PRL) (>25ng/ml), amenorrhea, galactorrhea, anovulation and infertility. From the perspective of pathological changes, it can be divided into tumor hyperprolactinemia, postpartum hyperprolactinemia, idiopathic hyperprolactinemia and iatrogenic hyperprolactinemia. The main clinical features are amenorrhea, infertility and galactorrhea.

Clinical manifestations: The most prominent manifestation of hyperprolactinemia is hypogonadism, which is caused by elevated PRL levels and is called hyperprolactinemic hypogonadism. Female patients may have decreased libido and loss of sexual desire, which will be relieved after treatment as PRL levels decrease. In women of childbearing age, hyperprolactinemic hypogonadism is mainly manifested by decreased menstruation or even amenorrhea, but it can also be manifested as menorrhagia or normal menstruation with infertility. Galactorrhea is another common symptom, seen in 30% to 80% of female patients. Most patients have well-developed breasts, which is in sharp contrast to the breast atrophy of natural menopausal women. Spontaneous galactorrhea is rare, and milk can only be seen when the nipples are squeezed. People with excessively high blood PRL levels do not have galactorrhea, which may be because excessively high PRL strongly inhibits the function of the gonads and significantly reduces the estrogen level. Patients with this disease have true galactorrhea, with fluid flowing out of both nipples. It is a milky or turbid white fluid that is rich in casein, whey protein and lactose, and should be distinguished from pseudogalactorrhea.

1. Laboratory examination for prolactin measurement: Take blood on an empty stomach 1-2 hours after getting up in the morning to measure PRL. The normal value of PRL on an empty stomach is 0.23-1.14nmol/L (5-25ng/ml). It is higher in women than in men. PRL has a peak secretion related to sleep, usually 1-2 hours after falling asleep. PRL in pregnant women can increase 10 times. The sucking of babies can cause an acute increase in PRL, which returns to normal after 2-3 hours. 4-6 weeks after delivery, PRL returns to pre-pregnancy levels. Prolactin>9.1nmol/L (200ng/L) is seen in prolactinoma and chronic renal failure. Other causes of hyperprolactinemia are postpartum breastfeeding, functional hyperprolactinemia, hypothalamic lesions such as sarcoma, histiocytosis, parasellar tumors, pituitary stalk lesions and some drugs that reduce dopamine production, including methyldopa, reserpine, tricyclic antidepressants, phenothiazines, etc. Metoclopramide increases prolactin to 4.5-6.8nmol/L (100-150ng/ml). Prolactin levels will also increase in people with primary hypothyroidism, chest wall diseases and spinal cord lesions. 2. Other auxiliary examinations (1) Children with TSH and GH deficiency can show decreased bone age on bone X-rays. (2) CT and MRI examinations are of great significance for diagnosis. These two examinations can show the location and size of the tumor, the presence of cystic changes, the invasion of the tumor into adjacent brain tissue, and the presence of hydrocephalus.

Diagnosis: For patients with galactorrhea and hypogonadism, the possibility of high PRL should be considered, and the diagnosis can be confirmed by measuring blood PRL. Normal male blood PRL generally does not exceed 0.68nmol/L (15ng/ml), and female blood PRL is generally 0.23-0.91nmol/L (5-20ng/ml). Since PRL is pulsatile and affected by many factors, it is best to repeat the measurement. It is worth noting that a small number of people have normal blood PRL in the morning but elevated blood PRL at night. These patients need to measure the nighttime blood PRL level and do a stimulation test. Commonly used stimulation tests include TRH test and metoclopramide (metoclopramide) test. The practice of TRH stimulation test is: fasting intravenous injection of TRH 400-500ug, and blood samples are collected at 0, 15, 30, 45, 60, 90, and 120 minutes to measure PRL. In normal people, PRL increases after TRH injection, with the peak value appearing 15 to 30 minutes after injection, and the peak value is about 5 times the base value (3 to 5 times for men and 5 to 8 times for women). The dose of metoclopramide test is 10 mg, which can be taken orally, or injected intravenously or intramuscularly. The PRL peak value appears 60 to 120 minutes after oral administration, and the peak value appears 20 to 60 minutes after intravenous or intramuscular injection. The peak value of normal people is more than 3 times the base value. Patients with PRL tumors are slow to respond to TRH and metoclopramide, and the multiple increase of PRL after administration is not as high as that of normal people, but the absolute value of the increase is higher than that of normal people.

Treatment 1. Antiprolactin drugs Antiprolactin drugs include bromocriptine, long-acting bromocriptine, tergoline, cabergoline, tergoline, methylergoline, quinagoline and lisuride.

2. Surgical treatment is suitable for patients with giant adenomas that present intracranial compression symptoms, who are ineffective with bromocriptine treatment, and who have giant adenomas and chromophobe cell tumors that secrete multiple pituitary hormones. The current transsphenoidal microsurgery is safe, convenient, and easy to perform, and its efficacy is similar to that of bromocriptine therapy. The use of bromocriptine before and after surgery can improve the efficacy. The disadvantages of surgery are that pituitary tumors have no obvious capsule and unclear boundaries, and it is not easy to be thorough or damaged during surgery, which may cause cerebrospinal fluid nasal fistula and postoperative hypopituitarism. It is worth noting that although preoperative bromocriptine treatment can shrink the tumor, it can cause tumor fibrosis, sclerosis, and adhesion of surrounding tissues, which is not conducive to surgical separation and resection. Therefore, if surgery is determined, medication can be temporarily stopped before surgery, and medication or radiotherapy can be supplemented after surgery. The mortality rate of microsurgical resection of pituitary prolactin adenomas is less than 0.5%, the incidence of temporary diabetes after surgery is 10% to 40%, and permanent diabetes and iatrogenic hypothyroidism are less than 20%. The probability of prolactin and ovulation returning to normal after surgery for microadenomas is 60% to 85%, while for macroadenomas it is 20% to 40%, and 85% of patients have normal visual fields.