Ninety percent of prolactin (PRL) elevations are due to pituitary tumors, which in women present as amenorrhea-overflow syndrome and can be diagnosed as pituitary PRL adenoma if the blood PRL is ≥200ug/L, even if not supported by imaging (MRI) findings. Other types of pituitary tumors or giant pituitary tumors can also cause elevated prolactin. So, what is the other 10% possibility? There are many causes, such as: (1) Drugs 1) Monoamine synthesis inhibitors 2) Monoamine depleting drugs Risperdal. 3) Dopamine receptor antagonists class Phenothiazine, chlorpromazine, haloperidol, butylbenzene and metoclopramide (methotrexate), morpholine, etc. can counteract the action of dopamine in the pituitary gland and cause overflow. 4) Adrenergic receptor antagonists (methadolol, medroxalo) 5) Tricyclic antidepressants 6) Estrogens Long-term use of oral contraceptives often causes breast overflow after discontinuation. Small doses of estrogen may stimulate the secretion of PRL. 7) Narcotics morphine and diacetylmorphine cause an increase in blood PRL, which is related to their involvement in the inhibition of central dopamine release. 8) Histamine H2 receptor blockers Cimetidine and ranitidine may stimulate increased PRL secretion through neurotransmitters, but the exact mechanism is not fully understood. (2) Primary hypothyroidism Most often occurs in children and adolescents due to increased thyrotropin-releasing hormone (TRH), which not only stimulates the secretion of thyrotropin (TSH) by the anterior pituitary gland, but also increases PRL secretion. After thyroxine replacement therapy, the symptoms of breast overflow may gradually disappear. (3) Primary hypoadrenocorticism Patients with this disease may sometimes have breast discharge and amenorrhea, with increased serum ACTH and PRL. (4) Renal insufficiency 65% of patients with chronic renal failure requiring hemodialysis have hyper-PRLemia, usually up to 150 ug/L. Female patients present with overflowing breasts. These patients have an abnormal response to short-term dopaminergic inhibition and TRH stimulation, and the metabolic clearance of PRL is decreased in the urine. PRL levels can usually be restored to normal after renal transplantation. (5) Cirrhosis Hyper-PRLemia can occur, with PRL values rising to two to three times normal, especially in patients with hepatic encephalopathy. This is due to the presence of pseudo-neurotransmitters. (6) Chest wall and breast diseases When the special nerve endings abundant in the nipple or areola part are stimulated, the nerve impulses reach the hypothalamus along the intercostal nerve and through the spinal cord, inhibiting the secretion of dopamine and leading to PRL secretion from the anterior pituitary gland. so mastitis, breast tumors or non-pregnant women who suck on the nipple for a long time can develop breast overflow. In the case of post-thoracotomy, burns, herpes zoster, etc., the overflow is caused by long-term stimulation of the intercostal nerve. (7) Spinal cord injury of the thoracic segment causes overflow of breast milk due to the involvement of the 4th to 6th intercostal nerve pairs. (8) Pregnancy In women with physiological menopause in early pregnancy, elevated blood PRL and full pituitary tissue on MRI are differentiated from pituitary microadenoma. Patients with a history of menopause of less than 6 months should be carefully followed up and a pregnancy test should be performed to rule out the possibility of pregnancy in suspicious cases. (9) Idiopathic hyper-PRLemia Idiopathic hyper-PRLemia is considered if there is no disease causing breast discharge or amenorrhea, no history of drug use, and no positive radiological findings such as MRI, but the blood PRL level is higher than normal. Idiopathic hyper-PRLemia can also lead to amenorrhea, breast discharge, infertility and decreased libido and can be treated with bromocriptine. Therefore, the diagnosis of prolactin pituitary tumor should be based on prolactin indicators and symptoms, but it is also necessary to exclude other causes and treat the primary disease as soon as possible. You can’t just put a “pituitary tumor” cap on it. One word from the doctor may affect the patient’s life. Note: Based on my many years of experience in treating pituitary tumors, the most common factors are highlighted in bold. The above is only for the reference of patients, once you find a similar situation, it is recommended to go to the hospital, do not delay the disease.