What Is Prolactinoma?
A Prolactinoma is the most common type of pituitary adenoma, which is a benign tumor of the pituitary gland. This tumor produces an excessive amount of the hormone prolactin. Prolactin is normally a hormone that initiates and maintains milk production in women. However, when it’s overproduced due to a tumor, it can lead to various health problems in both women and men.
The normal range for prolactin is 5–20 ng/mL (1 ng/mL = 1 μg/L = 21.2 mIU/L). Although prolactin levels in women are slightly higher than in men, they are typically below 25 ng/mL. Unless there’s excessive stress during blood collection, a single prolactin measurement is usually sufficient for diagnosis. However, to eliminate the stress factor during blood drawing, it’s more accurate for some patients to have a cannula placed beforehand and take 2-3 measurements at 15-20 minute intervals to calculate the average prolactin value. Sleep, exercise, emotional and physical stress, breast or chest wall stimulation, coitus, and a high-protein diet can lead to an increase in prolactin levels. Prolactin measurements should preferably be taken 4 hours after consuming protein-rich food.
Diagnosis and Differential Diagnosis:
Prolactin measurement is sufficient for diagnosis, and dynamic tests (TRH, L-Dopa, Domperidon, etc.) that investigate prolactin release are no longer recommended. In hyperprolactinemia thought to be caused by typical antipsychotic medications (phenothiazines, butyrophenones), the medication should be discontinued for 3 days, and the prolactin level should be re-measured.
However, some antipsychotics can cause hyperprolactinemia that lasts longer than three days. If the medication cannot be stopped, or if the prolactin elevation was present before medication use, or if it persists despite stopping the medication, imaging of the pituitary gland is essential after other pathological causes have been ruled out.
What Are the Prolactinoma Symptoms?
A Prolactinoma can lead to menstrual irregularities, absence of menstruation (amenorrhea), milk discharge from the breast (galactorrhea), fertility problems, decreased sexual desire, osteoporosis, increased hair growth, and weight gain in premenopausal women. In men, common symptoms include decreased sexual desire, erectile dysfunction, breast enlargement (gynecomastia), and rarely, nipple discharge. In both sexes, depending on the tumor size, pressure symptoms such as headaches and visual disturbances may occur.
What Is Macroprolactinemia?
Macroprolactinemia should be suspected in a patient without classic symptoms of hyperprolactinemia. The predominance of these large molecules in circulation is defined as macroprolactinemia. These high-molecular-weight forms of prolactin cannot pass through the capillary endothelium and bind to their receptors, thus showing no biological activity.
Macroprolactinemia is present when macroprolactin constitutes more than 40-60% of the total serum prolactin level. The most sensitive method for macroprolactin determination is gel filtration chromatography. However, due to its cost and complexity, this method is not routinely used.
The most commonly used method in daily practice is the polyethylene glycol (PEG) precipitation method. After measuring prolactin, the serum is treated with PEG. Normally, the percentage decrease in prolactin levels after PEG precipitation is evaluated to determine the presence or absence of macroprolactin (Table 1.3). If the reduction rate after PEG remains in the gray zone between 40-60%, the decision must be made based on the patient’s clinical picture. Anti-PRL antibodies may be associated with macroprolactinemia.
What Are the Causes Of Prolactinomas?
A Prolactinoma arises from the uncontrolled proliferation of lactotroph cells located in the pituitary gland. These cells normally produce the hormone prolactin, but when they transform into a benign tumor, an abnormal increase in hormone levels occurs.
Certain genetic factors can play a role in the development of the condition. Notably, albeit rare, cases linked to Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome have been observed. Furthermore, a decrease in dopamine’s effect can also elevate prolactin levels; this is often associated with the use of certain medications. This group includes antipsychotics (risperidone, haloperidol), serotonin-enhancing antidepressants, and stomach medications like metoclopramide. Additionally, in untreated hypothyroidism, increased TRH can indirectly stimulate prolactin secretion. Frequent daily stress and sleep problems can also cause temporary fluctuations in hormone levels.
Considering all these factors, it is crucial for individuals suspected of having a Prolactinoma to seek consultation from a specialist physician. For a comprehensive evaluation and an individualized approach in this matter, you can consult Uzm. Dr. Burcu Meryem Atak Sançmış, an Endocrinology Specialist.
What Are The Treatment Methods For Prolactinomas?
The treatment of a Prolactinoma typically begins with medication. Cabergoline, a dopamine agonist, is often the first choice, while Bromocriptine is considered an alternative option. Thanks to these medications, prolactin levels usually normalize within a few weeks for most patients, and a significant reduction in tumor size can be achieved.
Treatment Monitoring for Microprolactinomas (Adenom under 1 cm): Asymptomatic microprolactinomas (those with regular menstrual cycles and no bothersome galactorrhea) do not require treatment. However, it is necessary to treat those causing infertility problems and who are symptomatic. For premenopausal women with hypogonadism who are not planning pregnancy, oral contraceptives (OCs) may be given. Although there is no controlled study directly comparing OCs and dopamine agonists (DA) treatments, no increase in tumor size has been reported in patients using OCs or estrogen/progesterone replacement for 2 years. Furthermore, OC treatment is less expensive and has fewer side effects.
The medication dose is adjusted according to prolactin levels and patient tolerance. In the first month of treatment, prolactin levels, clinical findings, and drug side effects are monitored. If normoprolactinemia is achieved, complaints have decreased/disappeared, and there are no side effects, treatment is continued at the same dose. Thereafter, the patient is followed up every 6 months. A pituitary MRI control is performed 1 year after starting treatment. Gonadal functions normalize a few months after achieving normoprolactinemia. Sometimes, even if prolactin levels remain slightly elevated, gonadal functions and galactorrhea may improve.
In male microprolactinomas where DA treatment is ineffective or not tolerated, testosterone therapy or, in cases where fertilization is desired, human chorionic gonadotropin (hCG) may be considered. Surgical intervention is considered in cases where an adequate response to medication is not achieved or if it cannot be tolerated due to severe side effects.
Treatment Monitoring for Macroprolactinomas (Adenom over 1 cm): All macroprolactinomas should be treated with DA. At the start of treatment and during follow-up, additional comorbidities (other anterior pituitary hormone deficiencies, osteoporosis due to hypogonadism) should be assessed, and a visual field examination performed. Patients with pressure symptoms and pituitary hormone deficiency should be referred for surgery.
Especially in cases where the tumor presses on the optic nerve, transsphenoidal surgery is preferred, and successful results can be achieved. Radiotherapy is a method used in resistant cases where medical and surgical approaches remain ineffective.
Regular monitoring of patients throughout the treatment course is important. Prolactin levels are tracked with blood tests, while changes in tumor size are evaluated using magnetic resonance imaging (MRI).
How Should Treatment Be Managed For Long-Term Health Risks?
If a Prolactinoma is left untreated, it can lead to serious health problems such as infertility, sexual dysfunction, bone loss (osteoporosis), vision loss, persistent headaches, and psychological issues. Therefore, long-term and comprehensive follow-up of patients is of great importance.
The treatment process is not limited solely to restoring hormone balance. Regular monitoring of visual and neurological functions is critical for observing the tumor’s effect on nerve structures. Similarly, bone health should be regularly assessed due to the negative effects of high prolactin levels on bone density.
In this comprehensive follow-up process, Uzm. Dr. Burcu Meryem Atak Sançmış will provide reliable guidance with her personalized approach.
Frequently Asked Questions
What Is "False Prolactin"?
At very high prolactin levels, the test can yield misleadingly low results. Especially in macroprolactinoma cases (adenoma diameter 1 cm and larger), if low prolactin levels are detected despite the size, serial dilution is recommended.
Can A Prolactinoma Be Completely Treated?
Discontinuation of treatment for microprolactinomas (adenoma less than 1 cm): For these patients, after achieving normoprolactinemia, treatment should continue for at least 1-2 years. If the prolactin level has normalized in the following 2 or more years of follow-up and the adenoma has disappeared in imaging, the medication can be stopped. The medication dose should be gradually reduced, and if prolactin levels increase during this process, stopping the medication should not be considered. For women entering menopause, treatment can be discontinued.
Discontinuation of treatment for macroprolactinomas: Especially for adenomas of 1-1.5 cm, if the prolactin level has normalized under treatment and the adenoma has disappeared, discontinuing the medication may be considered. However, for tumors over 2 cm, where no tumor shrinkage is observed during treatment and prolactin levels do not normalize, the medication should not be stopped. The relapse risk after treatment discontinuation is 26-69%. Relapses frequently occur within the first year after discontinuing the medication. The most important parameters determining relapse are the initial prolactin level and tumor size. After discontinuing the medication, prolactin measurement should be done every three months in the first year, then annually. If the prolactin level increases during follow-up, a pituitary MRI should be requested. In cases of relapse, dopamine agonist treatment should be restarted.
The duration of treatment is, however, individual; it’s assessed by Uzm. Dr. Burcu Meryem Atak Sançmış through regular follow-up and imaging.
How Should Medical Treatment And Patient Monitoring Be Conducted During Pregnancy And Lactation?
Pregnancy and Prolactinoma: The potential proliferative effect of estrogen on prolactinomas carries the risk of tumor growth during pregnancy. The most important factor determining this risk is whether the patient was effectively treated beforehand. The risk of growth is 2.4% in pregnant microprolactinomas and 4.8% in macroprolactinoma patients who have undergone previous surgery, radiotherapy, or more than one year of DA use. For macroprolactinomas that have not been effectively treated, the risk is around 21%. Pregnancy should only be considered for macroprolactinomas after effective treatment has been achieved. Although there appears to be no problem with medication use during pregnancy, unnecessary medication use should be avoided until pregnancy is confirmed. By using mechanical contraception in the first few months before pregnancy, patients’ cycle lengths can be determined, and a pregnancy test can be performed if there is a cycle delay, minimizing fetal exposure to dopamine agonist medications. In microprolactinoma, treatment is paused. However, in macroprolactinomas with high growth potential, medication therapy should be continued. In monitoring prolactinomas during pregnancy, the presence of clinical compression symptoms (severe headache, visual impairment) is important. Serial prolactin measurements are not recommended. For microadenomas, clinical follow-up is performed every 3 months, and for macroadenomas, monthly. Visual fields can be checked every 2-3 months for macroadenomas. If compression symptoms appear, a non-contrast pituitary MRI should be performed.
Lactation and Prolactinoma: In the postpartum period (after birth), concerns about the pituitary gland decrease due to pituitary shrinkage, microinfarction, or necrosis of the prolactinoma, which can even lead to postpartum remission. Therefore, lactation (breastfeeding) is permitted, provided no compression symptoms are present. Lactation has no harmful effect on tumor growth. Postpartum evaluation should be done 2 months after birth or after breastfeeding has ceased. Remission may be prolonged after one or more pregnancies (40%).
Information Request Form
Fill out our Information Request Form to receive detailed information and to schedule an appointment.