Patients with microprolactinomas who are otherwise asymptomatic (no loss of libido or sexual dysfunction in men, or no menstrual irregularity or infertility in women) could be expectantly managed with serial prolactin determinations. Patients who have evidence of hypogonadism due to the hyperprolactinemia need to be treated to avoid the complications of prolonged hypogonadism (the most important is osteoporosis).
Whenever possible, medical treatment should always be sought first because of the high response rate and the relatively few complications. This applies to both micro- and macroprolactinomas. Even without therapy, 93% of microprolactinomas do not enlarge when followed over a period of 4-6 years; moreover, any increase in size is paralleled by an increase in prolactin serum levels. Therefore, if the initial brain imaging shows the presence of a microprolactinoma, follow up as well as response to treatment can be done by periodically checking serum prolactin levels.
prolactin levels should be checked periodically while on medical therapy. Once the prolactin levels have normalized, the dosages could be slowly tapered down to a lower dose; however, therapy is typically life-long as the tumor tends to grow back once the drugs are discontinued. Occasionally, the drugs can be discontinued after several years and the patient reevaluated. About 20% of patients are able to completely discontinue the medication and remain normoprolactinemic. The mainstay of medical treatment is dopamine receptor agonists (D2 agonists).
The first widely used dopaminergic agent used to treat prolactinomas was bromocriptine. Response rate is over 80-90%. Prolactin serum levels show a drop as early as 24 hours after starting therapy. In patients with macroadenomas, improvement in visual symptoms starts a few days to two weeks after therapy is initiated. Over 80% of patients will have a reduction in tumor size. The most common side effects are GI related (nausea and vomiting). Other side effects are orthostatic hypotension, nasal congestion, and occasionally, psychotic symptoms. Side effects can be minimized by starting with a lower dose at bedtime and gradually increasing it to BID dosing. If side effects persist, switch from oral to vaginal administration. Prolactin levels should be checked 4 weeks after starting therapy as well as 4 weeks after adjusting the dose. In amenorrheic patients who desire pregnancy, bromocriptine is the drug of choice due to its established fetal safety profile.
Cabergoine is another dopamine agonist. Unlike other agonists, cabergoline has a long half-life and therefore is administered twice weekly. It also appears to have fewer side effects compared to bromocriptine. Similar to bromocriptine, it can be given vaginally in the event of intolerable side effects. Due to its lower side effect profile and long half-life, cabergoline is often used as first line treatment except in patients who desire pregnancy (more data exist on the safety of bromocriptine exposure during early pregnancy). It is more expensive than bromocriptine.
Other Dopamine Agonists
Pergolide is a dopamine agonist used to treat Parkinson’s disease. It is less commonly used than bromocriptine but appears to be as effective. Another dopamine agonist, not available in the United States, but with efficacy comparable to that of bromocriptine, is quinagolide.
Surgery should not be offered as first line therapy due to lower success rates compared to medical therapy and a higher complication rate. The surgical cure rate for microadenomas is in the range of 50-60%, while for macroadenomas it is about 25%. Complications include visual loss, other cranial nerve injuries (CN III, IV, V), cerebrospinal fluid rhinorrhea, meningitis, and damage to other pituitary cells. Surgical mortality for macroadenomas is about 0.9%, while morbidity is 6-20%.
Radiotherapy is generally considered as third line treatment due to the high success rates of medical therapy and surgery when indicated.