A prolactinoma is a non-cancerous tumor that develops in the pituitary gland, a small organ located at the base of the brain. This tumor causes an overproduction of the hormone prolactin, a condition known as hyperprolactinemia. High prolactin levels disrupt normal bodily functions, leading to symptoms like irregular menstrual cycles, infertility, and spontaneous milk production. Management focuses on restoring hormonal balance and reducing tumor size. Given the high success rate of non-surgical methods, treatment often begins conservatively.
Defining Treatment Goals and Active Surveillance
The management of a prolactinoma centers on two main objectives: normalizing prolactin levels and shrinking the tumor mass. Normalizing prolactin levels reverses the symptoms of hyperprolactinemia, restoring fertility and normal sexual function, and resolving abnormal milk discharge. Tumor shrinkage is important for larger tumors (macroprolactinomas) to alleviate pressure on surrounding brain structures, especially the optic nerve.
In some cases, treatment is not immediately necessary, particularly for small tumors (microprolactinomas) measuring less than 10 millimeters that are not causing symptoms. This approach, termed “active surveillance,” involves regularly monitoring prolactin levels and tumor size with periodic Magnetic Resonance Imaging (MRI) scans. Active surveillance is an option when the tumor is small and stable, and the patient does not desire pregnancy. Treatment typically begins when symptoms appear, the tumor grows, or a patient wishes to address fertility issues.
First-Line Medical Therapy
The preferred initial treatment for a prolactinoma is medical therapy using dopamine agonists. These medications mimic dopamine, a neurotransmitter that naturally inhibits the pituitary gland’s release of prolactin. By stimulating dopamine D2 receptors on tumor cells, these drugs suppress prolactin secretion and lead to tumor size reduction. Medical therapy is highly effective, achieving normalization of prolactin levels and significant tumor reduction in most patients.
The two most commonly prescribed dopamine agonists are Cabergoline and Bromocriptine. Cabergoline is generally favored as the first-line choice because it has a greater affinity for the dopamine receptor and a longer half-life, allowing for less frequent dosing, typically once or twice a week. Studies show Cabergoline is more effective at normalizing prolactin levels and shrinking the tumor compared to Bromocriptine, with normalization rates reaching 80% to 90%.
Bromocriptine is a shorter-acting medication, often requiring daily or twice-daily dosing. While effective, it is associated with a higher incidence of side effects compared to Cabergoline. Common side effects of both medications include nausea, dizziness, lightheadedness, and headaches.
Starting with a low dose and gradually increasing it helps mitigate these side effects. Treatment is often long-term, requiring a minimum of two years of normalized prolactin levels and no visible tumor on MRI before considering supervised withdrawal. Though rare, patients receiving high doses of Cabergoline may require periodic echocardiograms to monitor for potential cardiac valve regurgitation.
When Surgery is Necessary
Surgery is typically reserved for patients who do not respond adequately to medical therapy (drug resistance) or cannot tolerate the side effects of dopamine agonists (intolerance). These issues affect a small percentage of patients. Another primary indication is a large tumor causing severe or rapidly worsening vision loss due to compression of the optic chiasm, which requires immediate decompression.
The standard procedure for prolactinoma removal is transsphenoidal surgery, where the surgeon accesses the pituitary gland through the nasal cavity and the sphenoid sinus. This approach is minimally invasive and avoids opening the skull. For very large or complex tumors, an endonasal endoscopic technique may be used to improve visualization.
Surgical success in achieving hormonal remission depends heavily on the tumor’s size and invasiveness. For smaller tumors (microprolactinomas), remission rates can reach 80% to 90% in experienced centers. However, for larger tumors (macroprolactinomas), the rate of long-term remission is lower, often around 50% to 60%.
Potential risks associated with transsphenoidal surgery include cerebrospinal fluid (CSF) leaks and damage to the normal pituitary gland, resulting in long-term hormonal deficiencies (hypopituitarism). Even after successful initial surgery, hyperprolactinemia recurs in about one-third of patients over time. If the tumor cannot be completely removed, surgery can still reduce the tumor bulk, allowing subsequent medical therapy to be more effective at a lower dose.
Targeted Radiation Options
Targeted radiation is a tertiary treatment option, typically reserved for cases where both medical therapy and surgery have proven unsuccessful. This method is used for residual tumor tissue that continues to grow or for patients who cannot undergo surgery. The technique most commonly used is Stereotactic Radiosurgery (SRS), which delivers a highly focused dose of radiation to the tumor with minimal exposure to surrounding healthy tissue.
SRS, often delivered via devices like the Gamma Knife or CyberKnife, is not an immediate fix; its effects are gradual. Tumor control (prevention of further growth) is achieved in over 90% of cases. Endocrine remission (normalization of prolactin levels without medication) has a longer latency period, with success rates reaching 40% to 55% at five to eight years post-treatment.
The main long-term side effect of radiation is the delayed onset of hypopituitarism, a deficiency in other pituitary hormones. This complication occurs in up to 25% of patients over several years following treatment, necessitating lifelong hormone replacement therapy. Given the slow therapeutic effect and the potential for long-term hormonal complications, radiation remains the last line of treatment.