Prolactinoma: Treatments
Lactotroph adenoma (prolactinoma) is a pituitary adenoma that secretes prolactin. It is called a macroadenoma if the size is more than 1 cm and a microadenoma if it is smaller than 1 cm. Treatment is essential if the size of the adenoma is large enough to cause a neurologic symptom such as headache or visual impairment. It is also advisable to treat the adenoma if it goes beyond the sella or if the size continues to increase. Prolactinoma is well tolerated in drug therapy compared to other types of pituitary adenomas. Dopamine agonist reduces prolactinoma size and prolactin secretion. The secretion of prolactin by Lactotroph adenoma is generally proportional to the size of adenoma. Serum prolactin values are usually no greater than 200 ng / mL for diameters less than 1 cm, 200 to 1000 ng / mL for diameters of 1.0 to 2.0 cm, and between 1000 ng / mL to 50,000 ng / mL for diameters exceeding 2 cm, ML. However, prolactinomas with poor differentiation do not secrete prolactin in large amounts, and their response to dopamine agonists is poor. Increased serum prolactin levels include amenorrhea, oligomenorrhea, infertility, galactorrhea, headache, visual impairment, decreased libido and energy due to hypogonadism, erectile dysfunction, and osteoporosis.
Dopamine agonist is a treatment of choice used in patients with hyperprolactinemia regardless of etiology. Dopamine agonists have cabergoline and bromocriptine, the former being used as first-line and the latter as second-line. These agents have the effect of reducing prolactin secretion and lactotroph adenoma size in more than 90% of patients (the extent of effect varies from patient to patient). Cabergoline or bromocriptine binds to dopamine receptors on the prolactinoma cell surface. Cabergoline is an effective, low-dose, ergot dopamine agonist administered once or twice a week. Cabergoline is associated with valvular heart disease when used in patients with Parkinson disease (PD). As the dose of the drug increases, the risk for valvular heart disease increases. High-dose cabergoline is used in PD, but low-dose cabergoline used in hyperprolactinemia is not known to be associated with valvular heart disease risk. In this sense, it is important to use the minimum capacity that can normalize the prolactin level. Patients taking cabergoline (eg, at doses greater than 2 mg / week) than the usual dose are recommended to undergo echocardiography every two years. Bromocriptine, on the other hand, has the disadvantage that nausea-like side effects are more pronounced than cabergoline, but bromocriptine is used as a first-line treatment in pregnant women or in pregnant women. This is because bromocriptine does not cause birth defects and is therefore more safe. In addition, there is a need to determine whether the patient is taking medications that interfere with dopamine agonist treatment. Examples include neuroleptic drugs, metoclopramide, sulpiride, domperidone, methyldopa, verapamil, and cimetidine.
Treatment of Lactotroph macroadenoma should always start with a dopamine agonist, regardless of the size of the adenoma or the degree of neurologic symptom. First, try using cabergoline, keep it if it's effective, and switch to bromocriptine if you do not have the reaction. Serum prolactin levels are monitored during treatment and the dose of cabergoline is increased once a month until the level is normalized. If serum prolactin levels remain at least normal for at least one year and prolactinomas are significantly reduced in size, the dosage of the dopamine agonist may be slowly reduced. In patients with a macroadenoma of 1.0 to 1.5 cm in size, serum prolactin levels remain at normal levels for more than 2 years and drug withdrawal may be considered in patients with no further adenomas on MRI. However, if the drug is discontinued, prolactin levels should be regularly measured and MRI scans should be followed to see if the size of the adenoma has increased. If the initial size of the Lactotroph adenoma is greater than 2 cm, the adenoma is still observed during MRI follow-up during treatment, or if the serum prolactin level is not normalized, the drug should not be discontinued. And it should not be stopped suddenly after menopause because hyperprolactinemia due to the increase in lactotroph adenoma size is likely to recur. On the other hand, transsphenoidal surgery is performed in women who do not have dopamine agonist treatment (when both first-line and second-line are ineffective) and pregnant women with a giant prolactinoma larger than 3 cm.
Treatment in this manner reduces serum prolactin levels, which are generally proportional to the extent of adenoma size reduction. The size reduction effect is more pronounced in macroadenoma. Reductions in serum prolactin usually occur in the first two to three weeks after initiation of dopamine agonist therapy. The size reduction of macroadenomas occurs after a decrease in serum prolactin levels. Diminished findings are generally observed within 6 weeks of treatment initiation. Once the size is reduced, the visual and pituitary functions return to normal. Especially in women, menstruation returns and fertility is restored after treatment begins. In men, testosterone secretion, sperm count, and erectile function return to normal. Dopamine agonist side effects include nausea, postural hypotension, mental haziness, and rarely nasal stuffiness, depression, alcohol intolerance, and constipation. However, these side effects can be prevented by starting with a small dose first.
If the prolactin level is normal for one year, the dose can be reduced. If there is no adenoma on the brain MRI, the drug can be discontinued. If the drug is discontinued, prolactin should be measured in the first 3 months and then every year thereafter. If prolactin increases to a significant level (especially in patients who initially had macroadenoma), MRI should be performed. You should then resume cabergoline treatment based on your previous treatment. However, hyperprolactinemia is recurrent in a large number of patients who discontinue medication. The longer the serum prolactin level remains normal for at least two years, and the less the adenoma is observed in MRI, the greater the likelihood of complete remission. Most patients with mac- roroadenoma remnants experience tumor recurrence within 7 years. And giant adenomas larger than 3 cm should be taken into account because they stop the dopamine agonist treatment and there is a risk of rapid growth within a few weeks. In the case of the above-mentioned patients, it is necessary to check whether the recurrence has not occurred through the regular follow-up even after the remission.
Dopamine agonist is a treatment of choice used in patients with hyperprolactinemia regardless of etiology. Dopamine agonists have cabergoline and bromocriptine, the former being used as first-line and the latter as second-line. These agents have the effect of reducing prolactin secretion and lactotroph adenoma size in more than 90% of patients (the extent of effect varies from patient to patient). Cabergoline or bromocriptine binds to dopamine receptors on the prolactinoma cell surface. Cabergoline is an effective, low-dose, ergot dopamine agonist administered once or twice a week. Cabergoline is associated with valvular heart disease when used in patients with Parkinson disease (PD). As the dose of the drug increases, the risk for valvular heart disease increases. High-dose cabergoline is used in PD, but low-dose cabergoline used in hyperprolactinemia is not known to be associated with valvular heart disease risk. In this sense, it is important to use the minimum capacity that can normalize the prolactin level. Patients taking cabergoline (eg, at doses greater than 2 mg / week) than the usual dose are recommended to undergo echocardiography every two years. Bromocriptine, on the other hand, has the disadvantage that nausea-like side effects are more pronounced than cabergoline, but bromocriptine is used as a first-line treatment in pregnant women or in pregnant women. This is because bromocriptine does not cause birth defects and is therefore more safe. In addition, there is a need to determine whether the patient is taking medications that interfere with dopamine agonist treatment. Examples include neuroleptic drugs, metoclopramide, sulpiride, domperidone, methyldopa, verapamil, and cimetidine.
Treatment of Lactotroph macroadenoma should always start with a dopamine agonist, regardless of the size of the adenoma or the degree of neurologic symptom. First, try using cabergoline, keep it if it's effective, and switch to bromocriptine if you do not have the reaction. Serum prolactin levels are monitored during treatment and the dose of cabergoline is increased once a month until the level is normalized. If serum prolactin levels remain at least normal for at least one year and prolactinomas are significantly reduced in size, the dosage of the dopamine agonist may be slowly reduced. In patients with a macroadenoma of 1.0 to 1.5 cm in size, serum prolactin levels remain at normal levels for more than 2 years and drug withdrawal may be considered in patients with no further adenomas on MRI. However, if the drug is discontinued, prolactin levels should be regularly measured and MRI scans should be followed to see if the size of the adenoma has increased. If the initial size of the Lactotroph adenoma is greater than 2 cm, the adenoma is still observed during MRI follow-up during treatment, or if the serum prolactin level is not normalized, the drug should not be discontinued. And it should not be stopped suddenly after menopause because hyperprolactinemia due to the increase in lactotroph adenoma size is likely to recur. On the other hand, transsphenoidal surgery is performed in women who do not have dopamine agonist treatment (when both first-line and second-line are ineffective) and pregnant women with a giant prolactinoma larger than 3 cm.
Treatment in this manner reduces serum prolactin levels, which are generally proportional to the extent of adenoma size reduction. The size reduction effect is more pronounced in macroadenoma. Reductions in serum prolactin usually occur in the first two to three weeks after initiation of dopamine agonist therapy. The size reduction of macroadenomas occurs after a decrease in serum prolactin levels. Diminished findings are generally observed within 6 weeks of treatment initiation. Once the size is reduced, the visual and pituitary functions return to normal. Especially in women, menstruation returns and fertility is restored after treatment begins. In men, testosterone secretion, sperm count, and erectile function return to normal. Dopamine agonist side effects include nausea, postural hypotension, mental haziness, and rarely nasal stuffiness, depression, alcohol intolerance, and constipation. However, these side effects can be prevented by starting with a small dose first.
If the prolactin level is normal for one year, the dose can be reduced. If there is no adenoma on the brain MRI, the drug can be discontinued. If the drug is discontinued, prolactin should be measured in the first 3 months and then every year thereafter. If prolactin increases to a significant level (especially in patients who initially had macroadenoma), MRI should be performed. You should then resume cabergoline treatment based on your previous treatment. However, hyperprolactinemia is recurrent in a large number of patients who discontinue medication. The longer the serum prolactin level remains normal for at least two years, and the less the adenoma is observed in MRI, the greater the likelihood of complete remission. Most patients with mac- roroadenoma remnants experience tumor recurrence within 7 years. And giant adenomas larger than 3 cm should be taken into account because they stop the dopamine agonist treatment and there is a risk of rapid growth within a few weeks. In the case of the above-mentioned patients, it is necessary to check whether the recurrence has not occurred through the regular follow-up even after the remission.
