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Prolactinoma

About 30% of pituitary tumors produce a hormone called prolactin. Normally, prolactin is made by specialized pituitary cells called lactotrophs. Under normal circumstances, prolactin is secreted at the time of breast-feeding. Prolactin increases the production of breast milk and suppresses secretion of LH and FSH, causing loss of menstrual periods in a breast-feeding woman and protecting her from becoming pregnant at the time when all the energy is needed to feed the baby. The role of prolactin in men is not known. Prolactin secretion is regulated by a hypothalamic hormone called dopamine. Dopamine suppresses prolactin production, and any process that diminishes the production of dopamine or its flow to the pituitary may cause prolactin to rise.

Normally, blood levels of prolactin are below 20 ng/ml. They may change during the menstrual cycle, as a result of pain or simply throughout the day. This is why mildly elevated prolactin level (below 40 ng/ml) without appropriate symptoms should not necessarily be viewed as the evidence of a disease process: it needs to be repeated first.

Clinically, symptoms of prolactin excess are simply an exaggerated extension of prolactin's normal function. Instead of increasing milk production (galactorrhea) and suppressing menstrual periods (amenorrhea) in a breast-feeding woman, it will cause amenorrhea and galactorrhea without any relations to pregnancy or breast-feeding. In men, high levels of prolactin may cause hypogonadism: low blood testosterone levels, and decrease in sex drive (libido) and sexual function. Prolactinoma is a benign (non-cancerous) pituitary tumor composed of lactotrophs (prolactin-producing cells).

Most prolactinomas in women are small, less than 10 mm (1/2 inch) in diameter, but some may be larger, up to 3-5 cm (2 inches) in diameter. In men, many prolactinomas are already large at the time of diagnosis. The larger the tumor, the higher the prolactin.

Large tumors may press on the optic nerves causing loss of vision or occupy cavernous or sphenoid sinuses. Large pituitary tumors often cause headache.

How is the diagnosis of a prolactinoma suspected?

Most often, young women notice irregular periods or amenorrhea, and/or milky breast discharge. In men, long-standing sexual dysfunction and/or loss of sex drive may prompt a visit to the primary care physician. Less frequently, patients may be primarily troubled by headaches, double vision or loss of peripheral vision.

How is the diagnosis made?

The physician will order a blood test. Elevated blood prolactin (above 50 ng/ml) will strongly suggest the diagnosis of hyperprolactinemia and further work-up will be ordered. Milder elevation of prolactin needs to be confirmed on a different occasion.

Does high prolactin mean that there is a pituitary tumor?

No. Often, certain drugs (antidepressants, blood pressure medications, etc.) may cause blood prolactin to rise as high as 100-150 ng/ml. Taking estrogens, including birth control pills, may elevate prolactin. Rarer causes of high prolactin are untreated primary thyroid failure, history of cranial radiation or even chest scars or trauma. Many diseases of the hypothalamic area (inflammation, other tumors) may also cause elevation of blood prolactin levels. In general, blood prolactin above 200 ng/ml almost always is diagnostic of a true prolactinoma. Lower prolactin levels may be seen in patients with small prolactinomas or in those with other conditions (see above). Very rarely, unusually large prolactinomas (bigger than 4 cm) may produce such high levels of prolactin that the laboratory may mis-read it as being quite low (20-40 ng/ml). This is called a "hook effect."

What are the next steps?

Your physician may want to do several other blood tests (for example: thyroid function, testosterone, LH and FSH) and sometimes the missing pituitary hormones need to be replaced even before the final diagnosis is reached. Also, your physician is likely to order a pituitary MRI.

 

How is a prolactinoma treated?

Small prolactinomas in young women may not require specific treatment unless infertility or galactorrhea are of concern. Small prolactinomas only rarely increase in size and may even disappear spontaneously. Larger tumors in women and tumors of any size in men are best treated with medications: Bromocriptine (Parlodel) Pergolide (Permax) or cabergoline (Dostinex) are used for this purpose. These medications reliably normalize prolactin and shrink the tumors. This may normalize the previously impaired pituitary function. The side effects (dizziness upon standing up, nausea and stuffy nose) may occur with all of these drugs, but Dostinex and Permax appear to be tolerated well in the majority of cases. These medications are likely to be taken for life, and stopping them will likely result in a rapid (1-4 weeks) re-growth of the tumor. Only if the tumor does not respond to these drugs or the patient cannot tolerate the side effects, do we recommend surgery. Small tumors (less than 1 cm) with relatively low prolactin (less than 200 ng/ml) can often be completely removed but they may recur after 1-3 years. Large tumors with very high prolactin can be debulked to relieve the pressure on the optic nerves, but are very unlikely to be removed completely. Radiation is rarely used for these tumors.


What is the prognosis?

Usually, medications fully restore normal sexual function and fertility. If the pituitary was irreparably damaged by the tumor, even then there are other medications that can restore fertility.