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Author: Paula J. Hillard, MD

Editor: Peter F. Schnatz, DO

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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:
    1. Hypothalamic-pituitary stalk damage due to trauma, radiation, Rathke’s cyst, infiltrative diseases, and parasellar tumors
    2. Pituitary disorders such as prolactinomas (adenomas), acromegaly, and macroprolactinemia
    3. Systemic disorders such as primary hypothyroidism, chest wall injury due to trauma, surgery, or herpes zoster, chronic renal failure with decreased clearance of prolactin, cirrhosis, and 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
  4. Idiopathic

The clinical manifestations of hyperprolactinemia in premenopausal women include oligomenorrhea, primary and secondary amenorrhea, anovulatory infertility, and galactorrhea. Patients with macroadenomas may have headaches and visual disturbances. In general, 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 reviewing history of breast manipulation, medications, pregnancy, headache, visual symptoms, hypothyroidism symptoms, and renal and liver disease. The physical examination should be directed for signs of hypothyroidism, hypogonadism, visual field loss, and chest wall injury.

Laboratory tests should include a prolactin and TSH. An MRI of the sella turcica is required to diagnose an adenoma and differentiate between other  lesions in the hypothalamic-pituitary region. Microadenomas are defined as prolactinomas less than 10 mm and macroadenomas are those greater or equal to 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%. Idiopathic hyperprolactinemia is diagnosed in the absence of pituitary and central lesions on MRI, and the absence of secondary causes of hyperprolactinemia.

Symptomatic patients with hyperprolactinemia may be treated with the dopamine agonists bromocriptine or cabergoline unless they have a stalk compressing lesion. Bromocriptine is less expensive and often used tried first. Cabergoline is more effective in reducing prolactin levels and adenoma size than bromocriptine, and has fewer side effects. Monitoring with prolactin levels is necessary to adjust medication dosages. Repeat MRIs may be indicated if symptoms persist or there is no response on prolactin levels. 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 macroadenoma 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, et al, Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Feb;96(2):273-88. doi: 10.1210/jc.2010-1692.

Initial Approval April 2012; Revised July 2018. Reaffirmed January 2020; Reaffirmed September 2021

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