Medication is an effective treatment for pituitary tumors. Although medication is a conservative treatment, it is very effective for prolactin adenomas and is the preferred treatment for pituitary prolactin adenomas.
Drug therapy is preferred for pituitary PRL adenoma. The main drugs used for the treatment of PRL adenoma are bromocriptan, pergolide, golitol, cartegolide and other dopamine agonists, whose mechanism of action is mainly to block the transcription of PRL gene at the mRNA level after binding to D2 receptors in the cell membrane, and to make the cytoplasmic structure of prolactinoma cells, especially to make the rough endoplasmic reticulum, which is the site of hormone synthesis and Golgi bodies, shrink significantly. The shrinkage of cells can cause different degrees of calcification, amyloid precipitation, perivascular and tissue interstitial fibrosis due to the enlargement of extracellular space, so the above mentioned drugs can not only reduce the blood PRL level, but also reduce the volume of PRL adenoma. In the pharmacological treatment of pituitary tumors, bromocriptan can normalize PRL and reduce tumor size in 80% to 90% of patients with pituitary PRL microadenomas and about 70% of patients with pituitary PRL macroadenomas, and 90% of female patients with normalized PRL regained menstruation and fertility. It is a long-acting dopamine agonist with a longer duration of action compared to bromocriptine, requiring only one or two doses per week, with better efficacy and fewer side effects that are more easily tolerated by patients, and may be effective in patients resistant to other dopamine agonists.
In the pharmacological treatment of pituitary tumors, long-term treatment with dopamine agonists requires regular monitoring of serum PRL levels and adjustment of drug doses according to PRL levels, while the frequency of MRI review can be determined on a case-by-case basis. In general, serum PRL levels are closely related to tumor size, and it is rare to see a significant increase in tumor size prior to a significant increase in PRL. Statistical analysis of a large number of cases indicates that approximately 95% of untreated pituitary PRL microadenomas do not increase in size further. In pituitary PRL microadenomas, only regular monitoring of serum PRL is required, and MRI should be repeated only when serum PRL levels are elevated. when pituitary PRL adenomas are large, aggressive adenomas that are actively growing, MRI may be repeated more frequently, for example, once every 2 to 3 years. The histological markers Ki-67 and cell proliferation nuclear antigen (PCNA) in aggressive adenomas only respond to the proliferative activity of the tumor cells, and their value for prognosis is limited.
The most common side effects include nausea, vomiting, dry mouth, dyspepsia, dizziness, postural hypotension, headache, nasal insufflation, and constipation. The above side effects mostly occur at the beginning of treatment and may be gradually tolerated by patients later, or may occur during treatment in some patients and be reversible after discontinuation of the drug. Patients with pituitary PRL adenoma rarely experience permanent side effects when taking 2.5-10 mg of bromocriptine daily or 0.25-2 mg of capsaicin weekly. However, there have been reports of pleural thickening, interstitial lung disease, plasma membrane fibrosis and cardiac regurgitation in patients with pituitary PRL adenomas in combination with Parkinson’s disease receiving high doses of bromocriptine, capsaicin or pergolide for prolonged periods of time. Therefore, cardiac ultrasound should be checked periodically in patients who are resistant to the drug and require high dose dopamine agonists.
Pregnancy may cause an increase in the size of pituitary PRL adenomas because estrogen stimulates the synthesis of prolactin and induces proliferation of prolactin cells. Approximately 3% of pituitary PRL microadenomas and 30% of pituitary PRL macroadenomas during pregnancy will show a significant increase in tumor size that causes clinical symptoms. If pregnancy is one of the goals of pharmacologic treatment of pituitary tumors, bromocriptine should be preferred because its safety has been more and more extensively documented, and statistics from a large number of cases show that its use in early pregnancy does not increase the incidence of spontaneous abortion or congenital malformations in the infant. A review of serum PRL is not necessary because PRL levels are not necessarily elevated in pregnancy and there is no correlation between PRL levels and tumor volume increase.
The main disadvantage of dopamine agonist drugs for pituitary tumors is the possibility of recurrence of hyperprolactinemia and re-increase in tumor size after discontinuation of the drug. However, long-term application of dopamine agonists to pituitary PRL adenomas can cause perivascular fibrosis and cellular suicide in pituitary tissue, suggesting that dopamine agonists may permanently normalize PRL levels. In the literature, it has been reported that pituitary PRL adenomas are treated with dopamine agonists for an average of 12-84 months and withdrawn after normalization of blood PRL, with an average follow-up of 6-60 months, of which 7-69% of patients continue to maintain normal blood PRL. It is generally accepted that after treatment with dopamine agonists, pituitary PRL adenomas can be discontinued on a trial basis when the following criteria are met: 1) normal PRL levels; 2) MRI indicates the disappearance of the tumor or a 50% or more reduction in tumor volume; 3) the tumor is more than 5 mm from the visual cross; and 4) the spongiosus is not invaded. Microadenomas can be discontinued directly, while macroadenomas should be discontinued gradually, and blood PRL levels should be monitored closely after discontinuation.
Estrogen may play a role in the formation of pituitary prolactin adenomas, and oral contraceptives have an anti-estrogen effect. Oral contraceptives may be used to treat hypogonadism in women with pituitary PRL microadenomas who do not have fertility requirements. Oral contraceptives are less expensive and have fewer side effects than dopamine agonists, but a mild increase in PRL may occur with oral contraceptives, and blood PRL levels need to be reviewed annually.
Although medication for pituitary tumors is very effective in treating pituitary prolactinomas, patients must go to the hospital for treatment and follow medical advice to prevent unnecessary problems.