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4/1/2012 - Paula J. Hillard, MD

Prolactin is mainly synthesized and secreted by the lactotroph cells in the pituitary gland. Elevations in serum prolactin usually result from conditions that cause hypersecretion of prolactin by the lactotrophs. These conditions include: (1) physiologic causes such as stress, nipple stimulation, sleep, exercise, coitus, pregnancy and lactation; (2) pathologic causes including (a) hypothalamic-pituitary stalk damage due to trauma, radiation, Rathke’s cyst, infiltrative diseases and parasellar tumors; (b) pituitary disorders such as prolactinomas, acromegaly, and macroprolactimemia; (c) systemic disorders such as primary hypothyroidism; chest wall injury due to trauma, surgery, herpes zoster; chronic renal failure with decreased clearance of prolactin, cirrhosis, malignancies such as renal and lung cancer; (3) pharmacologic causes due to some antipsychotics, gastric motility drugs, antihypertensives, dopamine receptor blockers, opiates, and H2 antihistamines; and (4) idiopathic.

The clinical manifestations of hyperprolactinemia in premenopausal women include oligomenorrhea, primary and secondary amenorrhea, anovulatory infertility, galactorrhea, and headaches or visual disturbances in patients with macroprolactinomas. In general, these symptoms correlate with the magnitude of the hyperprolactinemia. A serum prolactin concentration above 20-25 ng/mL is considered abnormally high in most laboratories. In cases of suspected drug-induced hyperprolactinemia, medication can be discontinued or a substitute given for 3 days, followed by repeat measurement of prolactin.

The evaluation should include a history of medications, pregnancy, headache, visual symptoms, hypothyroidism symptoms, and renal/liver disease. The physical examination should be directed for signs of hypothyroidism, hypogonadism, visual field loss, and looking for chest wall injury.

Laboratory tests should include a prolactin and TSH. An MRI of the sella turcica is required to diagnose a micro/macroadenoma or a mass lesion in the hypothalamic-pituitary region. Idiopathic hyperprolactinemia is diagnosed in the absence of pituitary and central lesions on MRI, and the absence of secondary causes of hyperprolactinemia. Microadenomas are defined as prolactinomas less than 10 mm and macroadenomas are those greater than 10 mm. Women with normal menstrual cycles and hyperprolactinemia have a very low incidence of clinically relevant disease, and may have macroprolactinemia. Macroprolactinemia is due to large polymeric forms of prolactin and circulating anti-prolactin autoantibodies. These forms of prolactin are less biologically active, consequently fewer patients are symptomatic and prolactinomas are present is only about 10-20%.

Symptomatic patients with hyperprolactinemia may be treated with the dopamine agonists bromocriptine or cabergoline. Cabergoline is more effective in reducing prolactin levels and prolactinoma size than bromocriptine and has fewer side effects. Monitoring with prolactin levels is necessary to adjust medication dosages. Repeat MRIs are dependent on the clinical situation. Treatment during pregnancy is usually limited to symptomatic patients and those with macroadenomas. Treatment resistance has been defined as a failure to normalize prolactin levels and to decrease macroprolactinoma size by >=50%, although recent studies have suggested that higher dose cabergoline regimens may be effective. Transsphenoidal surgery may be required for symptomatic patients with prolactinomas who do not respond or cannot tolerate high doses of cabergoline.

Further Reading:

Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA, Endocrine Society. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Feb;96(2):273-88.

Initial Approval April 2012; Revised July 2015; Reaffirmed January 2017


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