Prolactin adenoma is the most common functional pituitary adenoma, accounting for about 40-45% of functional pituitary adenomas in adults, with female patients aged 20-50 years old and a male to female ratio of about 1:10 in adults. standardized diagnosis and treatment of pituitary prolactin adenoma is of great significance in restoring and maintaining normal pituitary function and preventing tumor recurrence.
1.Clinical manifestations
2.Diagnosis
The diagnosis of prolactin adenoma can be made by combining typical clinical manifestations with laboratory tests of hyperprolactinemia and imaging examination of the saddle area.
2.1 Hyperprolactinemia: For patients with suspected pituitary prolactin adenoma, the requirements for venous blood sampling to measure prolactin are: eat a normal breakfast (type of carbohydrate, avoid protein and fatty foods), and take blood by venipuncture after a half-hour rest at 10:30-11:00 am. If serum prolactin >100-200ng/dl and other specific causes of hyperprolactinemia are excluded, the diagnosis of prolactin adenoma is supported.
2.2 Imaging of the saddle area: MRI-enhanced imaging of the saddle area helps to detect pituitary adenoma, and dynamic enhancement imaging helps to detect pituitary microadenoma.
3.Differential diagnosis (omitted)
4.Pharmacological treatment of pituitary prolactin adenoma
4.1 Indications for pharmacological treatment
The purpose of treatment is different for different sizes of pituitary prolactin adenoma. For patients with microprolactin adenoma, the aim of treatment is to control PRL level and preserve gonadal function and sexual function; for patients with large or huge prolactin adenoma, in addition to controlling PRL level and preserving pituitary function, it is necessary to control and reduce tumor volume, improve clinical symptoms and prevent recurrence.
Indications for drug therapy include: infertility, tumor-induced neurological symptoms (especially visual deficits), annoying lactation, chronic hypogonadism, altered pubertal development, and prevention of osteoporosis in women due to hypogonadism. Mild hyperprolactinemia, regular menstruation, women who want to get pregnant need to be treated.
4.2 Drug selection
Dopamine agonists, the treatment of choice for patients with PRL adenomas, are currently available as bromocriptine and cartegolide, and others as pergolide and quinolide. The drugs normalize PRL levels and significantly reduce tumor size in the majority of patients, and they are indicated for all sizes of tumors. Because pergolide and quinagolide are less commonly used, they are not recommended in this consensus.
4.2.1 Bromocriptine
Dosing: The initial dose for BRC (2.5 mg per tablet) treatment is 0.625-1.25 mg per day and is recommended to be taken orally at night with a snack before bedtime. Increase 1.25mg at weekly intervals until reaching two or three tablets per day. The side effects of upper gastrointestinal discomfort and upright hypotension are reduced by a slow dosing schedule and by taking with a snack at bedtime. A dose of 7.5mg per day is the effective therapeutic dose and can be gradually increased to 15mg per day if tumor volume and PRL are not well controlled. continued dosing does not further improve the treatment outcome and therefore high doses above 15mg are not recommended, but rather a change to CAB therapy is recommended. Since BRC has been proven to be safe and effective, and is relatively inexpensive and available in most medical departments in China, bromocriptine is the drug of choice recommended for the treatment of prolactin adenoma in China.
4.2.2 Cabergoline
The initial therapeutic dose of CAB (0.5mg per tablet) is 0.25-0.5mg per week, and the dose is increased by 0.25-0.5mg per month until the PRL is normal, and the dose rarely needs to exceed 3mg per week.
4.2.3 Drug side effects
BRC side effects include: headache, dizziness, nausea, vomiting, peptic ulcer and other gastrointestinal symptoms, nasal congestion, constipation, postural hypotension, and even shock manifestations in severe patients; fatigue, anxiety, depression, alcohol intolerance; drug-induced pituitary tumor stroke; CAB side effects are the same as bromocriptine, gastrointestinal side effects are milder than bromocriptine, other include psychiatric disorders, potential heart valve disease.
4.3 Prolactin microadenoma treatment
The primary goal of clinical treatment of PRL microadenomas is to preserve gonadal and reproductive function, and this goal is achieved significantly with drug therapy, i.e., the drugs are effective in controlling PRL levels, and with long-term effective DA therapy, microadenomas often shrink and sometimes disappear.
Since only 5-10% of microadenomas progress to macroadenomas, control of tumor size is not the primary goal of drug therapy, and women who do not want to have children can be treated without DA. Women with menopause can receive estrogen therapy, but PRL levels should be evaluated periodically, including review of dynamic-enhanced MRI to observe changes in tumor size.
4.4 Treatment of prolactinomatous adenomas and giant adenomas
Treatment of patients with prolactinomatous or giant adenomas involves reducing tumor size to improve clinical symptoms in addition to controlling PRL levels and preserving pituitary function. DA remains the treatment of choice for the vast majority of patients with prolactinomatous or giant adenomas, with the exception of acute tumor stroke-induced dramatic vision loss requiring emergency surgical decompression. DA treatment is usually effective in restoring visual function with results comparable to surgical cross-visual decompression. Therefore, patients with macroadenoma with visual field loss are no longer considered neurosurgical emergencies. However, in some drug-resistant cases, tumor size does not decrease significantly for several months of drug treatment. Sustained reduction or even disappearance of the tumor takes months or even years. Regular MRI review after drug treatment is required, once every 3 months after starting treatment, then once every 6 months after that, and at longer intervals thereafter.
The goal of treatment is to keep PRL levels as normal as possible, and it is best to lower PRL levels to the lowest possible value in order to minimize the size of the tumor or even to contribute to its disappearance. Even if the PRL level is reduced to normal, it is still necessary to take sufficient DA to further reduce the size of the tumor. When PRL levels remain normal for at least two years and tumor size is reduced by more than 50%, then DA tapering should be considered, because at this stage, low doses can maintain stable PRL levels and tumor size. However, discontinuation of treatment can lead to tumor enlargement and recurrence of hyperprolactinemia. For this reason, patients with large or giant adenomas need to be closely followed up after dose reduction or discontinuation.
5.Surgical treatment of pituitary prolactin adenoma
The choice of surgical treatment for pituitary prolactin adenoma should be based on a combination of the following: tumor size, blood prolactin levels, systemic condition, response to medication, the patient’s wishes, and fertility requirements. Microadenomas account for the majority of pituitary prolactin adenomas and the vast majority do not grow, so surgical intervention is not usually the first choice.
Surgical treatment aims to.
(1) Rapid relief of endocrine abnormalities and reduction of blood prolactin to normal range.
(2) Preserve normal pituitary function.
(3) Minimize tumor recurrence.
(4) Cerebrospinal fluid leak repair.
The vast majority of surgeries can be performed using a transnasal pterygoid sinus approach, and only a few drug-resistant invasive giant pituitary adenomas require craniotomy. In recent years, with the development of instruments and equipment such as neuronavigation and endoscopy and the improvement of minimally invasive surgical techniques, experienced surgical teams can make the transsphenoidal sinus approach more precise, safer, with less damage and fewer complications. Therefore, transsphenoidal approach is another option for patients with pituitary prolactin adenoma in addition to drug treatment.
Indications for surgery.
(1) Pituitary microadenomas that have failed to respond to drug therapy for 3 to 6 months or have poor results.
(2) Those who cannot tolerate the large response to drug therapy.
(3) Huge pituitary adenoma with obvious visual pathway compression, and drug therapy cannot control blood prolactin and reduce tumor size. Or after 3 to 12 months of drug treatment, the blood prolactin level drops to normal, but the tumor volume remains unchanged, it is necessary to consider the possibility of pituitary non-functional adenoma.
(4) Invasive pituitary adenoma with cerebrospinal fluid nasal leakage, or those with cerebrospinal fluid nasal leakage after drug treatment.
(5) Those who have insufficient psychological tolerance to live with tumor or refuse to take long-term medication.
(6) Those who have a stroke of pituitary tumor caused by medication or other reasons, showing severe headache and acute vision loss.
(7) Pituitary macroadenoma with cystic degeneration, where drug therapy usually fails to reduce the size of the tumor.
(8) Experienced surgeons believe that there is a high expectation of total surgical resection and that the patient’s wishes for surgery are fully considered.
There are almost no absolute contraindications to surgery, and the vast majority of relative contraindications are associated with poor general status and organ dysfunction. In these patients, treatment to improve the general condition should be performed prior to surgical treatment.