Prolactinomas

Posted by Graham McMahon • April 2nd, 2010

Our latest Clinical Practice article comes from Dr. Anne Klibanski of Massachusetts General Hospital and Harvard Medical School.

Prolactinomas are the most common type of secretory pituitary tumor.  Typically benign, they are classified according to size; microadenomas are less than 10 mm in diameter, and macroadenomas 10 mm or more. Serum levels of prolactin in patients with prolactinomas are usually proportional to the tumor mass.

Clinical Pearls

What is the typical presentation of prolactinomas in women?

Clinical symptoms and signs of hyperprolactinemia in women include oligoamenorrhea, infertility, and galactorrhea. In women with hyperprolactinemia who continue to have menses, luteal-phase abnormalities can lead to infertility. Estrogen deficiency in amenorrheic women with untreated prolactinomas causes low bone mass, which is associated with an increased risk of fracture.

What is the typical presentation of prolactinomas in men?

In men, hyperprolactinemia may lead to hypogonadism, decreased libido, erectile dysfunction, infertility, gynecomastia, and, in rare instances, galactorrhea. Decreased bone mass and anemia result from testosterone deficiency. In contrast with women, who usually present with microadenomas, most men present with macroadenomas, often with headache, visual symptoms, or both, in addition to hypogonadism.

Morning Report Questions

Q: Other than prolactinoma, what are other causes of hyperprolactinemia?

A: Secretion of prolactin is under tonic inhibitory control by hypothalamic dopamine; levels of prolactin can be increased in the presence of other tumor types, inflammatory disorders such as lymphocytic hypophysitis, cysts (e.g., Rathke’s cysts, which disrupt dopamine transport down the pituitary stalk), or medications that interfere with normal secretion of hypothalamic dopamine. These medications include antidepressants and antipsychotic agents (risperidone, in particular), other dopaminergic blockers (e.g., metoclopramide and sulpiride), some antihypertensive agents, opiates, and H2-receptor blockers.

Q: What treatment rapidly normalizes prolactin levels, restores reproductive function, reverses galactorrhea, and decreases tumor size in most patients with a prolactinoma?

A: Dopamine agonists are the primary therapy for both microadenomas that require treatment and macroprolactinomas. They rapidly normalize prolactin levels, restore reproductive function, reverse galactorrhea, and decrease tumor size in most patients. Dopamine agonists include bromocriptine and cabergoline (both ergot derivatives) and quinagolide (not approved for use in the United States).

Table 1. Indications for Therapy in Patients with Prolactinomas.

One Response to “Prolactinomas”

  1. Lucretia van den Berg MD FRCPC says:

    Dr. Anne Kilbanski suggests that hyperprolactinemia need not be treated in postmenopausal women.

    However substantial laboratory and in vitro data suggest that high prolactin levels play a role in mammary carcinogenesis. There are epidemiologists who opine that increased plasma prolactin concentrations are associated with an increased risk of postmenopausal breast cancer, particularly for estrogen receptor+/progesterone receptor+ cancers, independent of estradiol levels. High prolactin levels have been associated with a 60% increased risk of estrogen receptor (ER) positive tumors, but not ER negative tumours. ( Shelley S. Tworoger, A. Heather Eliassen, Bernard Rosner, Patrick Sluss and Susan E. Hankinson. Plasma Prolactin Concentrations and Risk of Postmenopausal Breast Cancer: Cancer Research 64, 6814-6819, September 15, 2004).

    Studies of survival have suggested that high pretreatment prolactin levels were associated with treatment failure, earlier recurrence, and worse overall survival. ( Tworoger, Shelley S. | Hankinson, Susan E. Prolactin and Breast Cancer Etiology: An Epidemiologic Perspective. Journal of Mammary Gland Biology and Neoplasia: Volume 13, Number 1 / March, 2008).

    From the Netherlands, Britain, and the Channel Islands (Guernsey) comes a further proposal that an elevated prolactin level may not be benign. In post-menopausal women who developed breast cancer, the prolactin levels were significantly elevated, being at or above the 70th percentile for the controls. In their group of patients the results were thought to be consistent with prolactin acting as a late-stage tumour promoter. ( H. G. Kwa, F. Cleton, D. Y. Wang , R. D. Bulbrook, J. C. Bulstrode , J. L. Hayward, R. R. Millis, J. Cuzick. A prospective study of plasma prolactin levels and subsequent risk of breast cancer: International Journal of Cancer: Volume 28 Issue 6, Pages 673 – 676 published online 2006).

    The prolactin connection to breast cancer is counterintuitive, given that hyperprolactinemia contributes to hypoestrogenemia. No clear guidelines have been established for the treatment of hyperprolactinemia in postmenopausal women. Nevertheless, given the uncertainty which has long been present (Halbreich U, Shen J, Panaro V. Are chronic psychiatric patients at increased riskfor developing breast cancer? Am J Psychiatry 1996;153:559–60), it may be prudent to treat elevated prolactin in postmenopausal women, at least until the issue has been clarified.

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