A 42-year-old obese woman with type 2 diabetes, diabetic retinopathy, hypertension, and hirsutism presents to discuss an elevated prolactin level of 144.8 ng/mL (normal range, 4.8 to 23.3 ng/mL) found by her Ob-Gyn two months ago. She complained of galactorrhea and no menses for one year. A repeat prolactin level was also elevated, at 109 ng/mL.
A pituitary MRI with contrast showed a “subtle area of delayed enhancement in the right pituitary, consistent with a 5-mm microadenoma.” The patient was prescribed the dopamine agonist cabergoline (0.25 mg, to be taken twice a week), with a plan to follow up in two to three months.
Q: In obtaining a thorough history, what additional questions should be asked of this patient?
There are many causes of hyperprolactinemia. Factors that can increase prolactin secretion include pregnancy, nursing, physiologic stress, estrogen use, polycystic ovary syndrome, hypothyroidism, and chronic renal or hepatic failure. Head trauma, use of certain medications (verapamil, neuroleptics, antipsychotics, and antidepressants), and presence of nonsecretory sellar or suprasellar masses can also increase prolactin levels.
In general, signs and symptoms are due to either the effect of excess hormone secretion (ie, galactorrhea and amenorrhea) or local compression (ie, new-onset or persistent headache, dizziness, visual changes, and vision loss). A review of medications, including estrogen therapy, and history of fertility or gonadal dysfunction should be documented. Elevated prolactin levels can result in secondary hypogonadism.1
Note: While the case patient is female, it should be emphasized that prolactinomas do occur in men. The incidence is, overall, low. In addition to the symptoms listed above, men can present with decreased libido and infertility.1
Q: What additional diagnostic tests should be ordered as part of the work-up of galactorrhea and amenorrhea in this patient?
Laboratory evaluation should include a repeat serum prolactin test, measurements of TSH and free T4, and a pregnancy test. (A serum testosterone level should be checked in men.) If the results come back normal and if other diagnoses are excluded, the most likely diagnosis is a prolactinoma. In this case, a pituitary MRI should be obtained. Visual field testing can be performed in individuals with specific visual complaints, especially loss or impairment of peripheral vision.
Q: What is the incidence of prolactinoma in the general population?
Prolactin-secreting adenomas, or prolactinomas, are the most common type of pituitary adenoma, accounting for approximately 60% overall.1 They occur at a frequency of six to 10 cases per million each year.2 Prolactinomas are almost always benign; malignant tumors are extremely rare.3
Tumors are classified as microadenomas or macroadenomas, depending on the size. A microadenoma is defined as an intrasellar mass less than 10 mm in diameter. A macroadenoma, defined as larger than 10 mm in diameter, can cause enlargement of the sella turcica.1,4 The larger the size of the prolactinoma, the greater the prolactin level and higher the likelihood of mass-effect symptoms.4
Q: What are the options for treatment of a prolactinoma?
There are several options for treatment of prolactinomas. After discussing all of the available options with the patient, the choice of therapy should be determined by the patient’s desires and potential plans for pregnancy. It is acceptable to observe the tumor with serial MRIs and serum prolactin measurements, provided the tumor is very small and the patient is asymptomatic.4
Medication therapy involves treatment with a dopamine agonist, which directly inhibits prolactin secretion by the tumor and therefore suppresses tumor growth. The goal of medication therapy is to suppress the prolactin level to normal range and restore gonadal function. The two dopamine agonists used are bromocriptine and cabergoline.
Bromocriptine was the first drug available in the United States to effectively treat pituitary adenomas. Its most common adverse effects include nausea, vomiting, dizziness, and postural hypotension. These effects can be minimized or avoided if the drug is started at a low dose, gradually increased, and taken at bedtime. The adverse effects usually subside with continued use; however, in some patients they persist and therefore the drug has to be discontinued.
Cabergoline is a non-ergot dopamine agonist that is more efficacious, overall better tolerated, and longer acting than bromocriptine. It is dosed twice weekly, whereas bromocriptine is dosed once daily.4 One factor to consider in a female patient is whether she is of child-bearing age and is interested in conception. Both bromocriptine and cabergoline are designated as category B; however, in animal studies cabergoline has been associated with maternal toxicity, increase in fetal death, and growth retardation and death due to decreased milk secretion by the mother. Therefore, it should only be used during pregnancy if the need has been clearly established.
Dopamine agonists are approximately 80% to 90% effective in decreasing prolactin levels and reducing tumor size in microadenomas and 60% to 70% in macroadenomas. The major drawback of using medication is that it does not always provide permanent results. Hyperprolactinemia and tumor growth can resume upon discontinuation of the drug, even if the patient has taken it for several years.1 The rate of recurrence after discontinuing therapy can be anywhere from 26% to 69%, and the highest likelihood occurs within a year of withdrawal.4 Close clinical follow-up is thus important.
Surgery, typically a transphenoidal resection, is performed by a neurosurgeon. Success of surgery is based on tumor size and basal prolactin level prior to the procedure. It is more effective in restoring normal prolactin levels and resolution of symptoms in microadenomas than in macroadenomas. Progressive vision loss, pituitary apoplexy, and intolerance to dopamine agonists are indications for surgery.1
Radiation therapy is reserved for those patients who have residual tumors postsurgery and have not responded to or are intolerant to dopamine agonists. Response to radiation is slow; it can sometimes take several years to achieve full effect. Gamma-knife radiation is sometimes used, but experience with this procedure is limited thus far in prolactinomas.
Overall, the vast majority of prolactinomas are benign and fairly straightforward to manage clinically.3
1. Greenspan F, Gardner D. Basic & Clinical Endocrinology, 7th ed. New York: McGraw-Hill; 2004.
2. Ciccarelli A, Daly A, Beckers A. The epidemiology of prolactinomas. Pituitary. 2005;8(1):3-6.
3. Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273.
4. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society Clinical Practice Guideline. J Clinical Endocrinol Metab. 2011;96(2):273-288.