Physiologic elevation of PRL occurs in pregnancy and lactation. Otherwise, PRL-secreting pituitary adenomas (prolactinomas) are the most common cause of PRL levels >200 µg/L. Less pronounced hyperprolactinemia is commonly caused by medications (risperidone, chlorpromazine, perphenazine, haloperidol, metoclopramide, opiates, H₂ antagonists, amitriptyline, selective serotonin reuptake inhibitors [SSRIs], verapamil, estrogens), pituitary stalk damage (tumors, lymphocytic hypophysitis, granulomas, trauma, irradiation), primary hypothyroidism, or renal failure. Nipple stimulation may also stimulate PRL secretion.

In women, amenorrhea, galactorrhea, and infertility are the hallmarks of hyperprolactinemia. In men, symptoms of hypogonadism (Chap. 177: Disorders of the Male Reproductive System) or mass effects are the usual presenting symptoms, and galactorrhea is rare.

Fasting PRL levels should be measured; when clinical suspicion is high, measurement of levels on several different occasions may be required. If hyperprolactinemia is present, nonneoplastic causes should be excluded (e.g., pregnancy test, hypothyroidism, medications).

If the pt is taking a medication that is known to cause hyperprolactinemia, the drug should be withdrawn, if possible. A pituitary MRI should be performed if the underlying cause of PRL elevation is unknown. Resection of hypothalamic or sellar mass lesions can reverse hyperprolactinemia due to stalk compression. Medical therapy with a dopamine agonist is indicated in microprolactinomas for control of symptomatic galactorrhea, for restoration of gonadal function, or when fertility is desired. Alternatively, estrogen replacement may be indicated if fertility is not desired, but tumor size should be carefully monitored. Dopamine agonist therapy for macroprolactinomas generally results in both adenoma shrinkage and reduction of PRL levels. Cabergoline (initial dose 0.5 mg a week, usual dose 0.5–1 mg twice a week) or bromocriptine (initial dose 0.625–1.25 mg qhs, usual dose 2.5 PO three times a day) are the two most frequently used dopamine agonists. Cabergoline is the more effective and better-tolerated drug. These medications should initially be taken at bedtime with food, followed by gradual dose increases, to reduce the side effects of nausea and postural hypotension. Other side effects include constipation, nasal stuffiness, dry mouth, nightmares, insomnia, or vertigo; decreasing the dose usually alleviates these symptoms. Dopamine agonists may also precipitate or worsen underlying psychiatric conditions. Cardiac echocardiography is prudent before starting cabergoline therapy as there has been concern about an association with valvular heart disease. In pts with microadenomas successfully treated (normal PRL, full tumors shrinkage), therapy may be withdrawn after 2 years, followed by careful monitoring for tumor recurrence. Spontaneous remission of microadenomas, presumably caused by infarction, occurs in some pts. Surgical debulking may be required for macroprolactinomas that do not adequately respond to medical therapy.

Women with microprolactinomas who become pregnant should discontinue dopaminergic therapy, as the risk for significant tumor growth during pregnancy is low. In those with macroprolactinomas, visual field testing should be performed at each trimester. A pituitary MRI should be performed if severe headache and/or visual defects occur.