What are the causes of hyperprolactinemia?

  Because serum prolactin (PRL) levels are affected by many factors, blood should be collected early in the morning on an empty stomach for measurement. If the prolactin level is less than three times the upper limit of normal, it should be measured at least twice to determine the presence of hyperprolactinemia.  Hyperprolactinemia can be divided into three categories according to the cause: (a) Physiological factors Pregnancy, breastfeeding, exercise, sleep, sexual intercourse, and stress can all cause hyperprolactinemia. Elevated PRL in stressful situations such as surgery is related to the degree of stress, and once the stress is relieved, PRL will return to normal.  (ii) Pathological factors In patients with chronic renal insufficiency, the glomerular filtration rate of PRL is reduced, which can lead to a moderate increase in serum PRL. About one-third of patients with kidney disease have hyperprolactinemia. Mildly elevated PRL levels are present in about 20% of patients with hypothyroidism, probably due to long-term hypothyroidism or inadequate treatment of hypothyroidism, resulting in pituitary hyperplasia, leading to pathophysiological changes similar to pituitary tumors. In this case, thyroid hormone supplementation can reduce PRL levels and shrink the hyperplastic pituitary gland.  Larger non-functional pituitary tumors, hypothalamic granulomatous lesions, craniopharyngiomas, and suprasellar surgery can cause compression of the pituitary stalk or damage to dopamine neurons, resulting in decreased levels of dopamine reaching the prolactin cells, which can lead to the development of hyperprolactinemia, when PRL levels generally range from 20 μg/L to 100 μg/L.  The use of dopamine receptor agonists can reduce PRL levels. The cause of idiopathic hyperprolactinemia is unknown and may be due to altered hypothalamic regulation. The diagnosis can be established only when physiological, pharmacological and other pathological factors are excluded. Less than 10% of these patients may have a small prolactin microadenoma that is not detected by imaging. About 30% of patients with idiopathic hyperprolactinemia resolve on their own; 10%-15% have further elevated PRL levels; the rest have stable PRL levels.  Because of the homology between prolactin cells and growth hormone cells, about 50% of patients with acromegaly have hyperprolactinemia; in addition, because human GH has the same prolactinogenic effect as PRL, patients with growth hormone tumors may have similar symptoms and signs as those with prolactinomas, which should be investigated. Hyperprolactinemia is present in about 30% of patients with polycystic ovary syndrome. Other pituitary lesions, such as lymphocytic pituitaryitis and TSH tumors, may also cause hyperprolactinemia.  (For example, antipsychotic drugs can increase PRL levels by reducing or antagonizing the effects of dopamine. Other drugs such as anesthetics, antidepressants, and antihistamines can also cause hyperprolactinemia. Most patients with drug-induced hyperprolactinemia have PRL <150 μg/L. It is important to note that pituitary imaging should be performed even if PRL levels are only mildly elevated, as prolactinomas may coexist with other factors that cause hyperprolactinemia.