Prolactinoma is a hormone–active tumor of the anterior pituitary gland that produces an excessive amount of the hormone prolactin. It is manifested by pathological milk secretion unrelated to childbirth (galactorrhea), irregular menstruation or their absence in women, decreased potency and sexual desire in men, with tumor progression – headache, impaired vision and consciousness. Depending on the degree of tumor activity, treatment is conservative or surgical, relapses are possible, full recovery occurs only in a quarter of cases.
Meaning
Prolactinomas belong to the group of benign adenomas, the most common among pituitary tumors (up to 30%), are extremely rarely malignant and are observed in women of the childbearing age group 6-10 times more often than in men. The dimensions of prolactinomas usually do not exceed 2-3 mm, however, in men, as a rule, there are large adenomas more than 1 cm in diameter.
Prolactinomas are hormone-active pituitary adenomas that secrete prolactin, a “milk hormone” that stimulates postpartum lactation in women. Normally, men also produce prolactin in smaller quantities. Together with luteinizing and follicle-stimulating hormones, prolactin has a regulating effect on reproduction and sexual function. In women, these hormones provide estrogen synthesis, menstrual cycle regulation and ovulation, in men – testosterone production and sperm activity.
Excess prolactin secreted by prolactinoma (hyperprolactinemia) suppresses estrogenogenesis in women and leads to anovulation and infertility. In men, prolactin-secreting adenoma causes erectile dysfunction, gynecomastia and loss of libido.
Causes
The causes of the development of prolactinoma are reliably unknown. However, in some patients with pituitary adenomas (including prolactinoma), the presence of genetic disorders is noted – multiple endocrine neoplasia type I – a hereditary disease characterized by excessive secretion of hormones by the parathyroid, pancreas, pituitary gland and multiple peptic ulcers. In some cases, there is a tendency to hereditary development of prolactinoma.
Modern endocrinology, together with genetics, continues research to identify the genes responsible for the occurrence of prolactinoma.
Classification
According to their size and location within the pituitary fossa, prolactinomas are divided into two groups:
- intracellar microprolactinomas – prolactin-secreting adenomas up to 1 cm in diameter, not extending beyond the Turkish saddle;
- extracellular macroprolactinomas are prolactin-secreting adenomas with a diameter of more than 1 cm, extending beyond the Turkish saddle.
The size of the prolactinoma affects the symptoms caused by local deformation and determines the choice of therapy method.
Symptoms
Manifestations of prolactinoma can be caused by both an increased level of prolactin and compression of the surrounding brain tissue by the tumor. The severity of symptoms directly depends on the size of the prolactinoma. With macroprolactinomas that squeeze the optic nerves, visual disturbances are noted (narrowing of the visual fields, difficulties in recognizing side objects, double vision). Compression of the macroprolactinoma of the visual intersection can lead to blindness.
Large prolactinomas cause symptoms from the central nervous system: headache, depression, anxiety, irritability, emotional instability. In addition, macroprolactinomas, exerting pressure on the pituitary gland, cause a violation of the production of other hormones of this gland.
In women
An early manifestation of prolactinoma in women is a change in the rhythm of the menstrual cycle from oligo- and opsomenorrhea to amenorrhea. Violation of the formation of follicle-stimulating and luteinizing hormones leads to the absence of ovulation and the impossibility of conception.
The physiological effect of prolactin is manifested in the production and excretion of milk from the mammary glands (galactorrhea) in the absence of pregnancy. Milk can be released drop by drop when pressing on the nipple, or independently – periodically or constantly. Galactorrhea in prolactinoma is not associated with diseases of the mammary glands, including breast cancer, but often causes the subsequent development of mastopathy.
Hyperprolactinemia, accompanying the development of prolactinoma, leads to the leaching of minerals from bone tissue and the development of osteoporosis. Osteoporosis, caused by a change in the structure of bone tissue, causes an increase in bone fragility. Estrogen deficiency causes fluid retention and weight gain. If the course of prolactinoma is accompanied by hyperandrogenism, then a woman develops hirsutism and acne. In women, microprolactinomas are more common.
For men
The effect of prolactinoma on the male body is expressed in a decrease in testosterone levels and a violation of spermatogenesis. As a result, there is a weakening of sexual desire, potency, erectile dysfunction, infertility develops. The mammary glands increase in size (gynecomastia), sometimes galactorrhea develops. Among other manifestations of prolactinoma in men, testicular atrophy, decreased facial hair growth, osteoporosis and muscle weakness are noted.
In men, prolactinomas often reach large sizes (macroprolactinomas).
Diagnostics
A highly informative method for suspected prolactinoma is an MRI of the brain with a targeted examination of the pituitary gland with a contrasting substance gadolinium. Magnetic resonance scanning allows you to identify the outlines of small adenomas, their intracellar or extrasellar location, as well as tumors located in soft tissue formations (cavernous sinus, in the area of carotid arteries, etc.).
With macroprolactinomas, CT of the brain is more applicable, because it visualizes bone structures well (the base of the Turkish saddle is the anatomical area of the pituitary gland).
Laboratory determination of prolactin levels in blood serum is recommended to be carried out three times, on different days to exclude accidental or stress-related fluctuations in its values. Prolactin level > 200 ng/ml (or > 9.1 nmol/L) indicates in favor of prolactinoma (prolactin norm for women –
With an increase in prolactin concentration to 40-100 ng / ml (hypothyroidism, chest injuries, insufficiency of kidney and liver functions, taking medications that stimulate prolactin production, functional disorders of the hypothalamic-pituitary system.
Of the stimulation samples, the test with tyroliberin is the most indicative. Normally, after intravenous administration of the drug, after 15-30 minutes, prolactin production increases, and its concentration is at least 2 times higher than the initial level. In patients with prolactinoma after stimulation, prolactin synthesis either remains the same or increases by less than 2 times. With hyperprolactinemia of non-tumor genesis, a reaction to tyroliberin is observed, close to normal.
If there are complaints from the organs of vision, the patient is examined by the fields of vision and consulted by an ophthalmologist. To exclude osteoporosis, bone density is determined by densitometry.
Treatment
Usually, the treatment of prolactinoma is medicamental, aimed at reducing the level of prolactin. The selection of the treatment regimen and optimal doses of drugs is carried out by an endocrinologist in accordance with the data of additional research methods. Drugs are used: bromocriptine, levodopa, ciproheptadine, cabergoline. Taking bromocriptine causes a decrease in prolactin concentration to normal within a few weeks in 85% of patients. The advantages of cabergoline are prolonged action (1-2 doses per week are enough), the smallest number of side effects than that of bromocriptine.
As the drugs are taken, the size of prolactinoma and prolactin secretion decrease, vision improves; small microadenomas may disappear altogether. In women, the menstrual cycle is normalized, fertility (the ability to conceive a child) is restored. In men, testosterone levels increase, sexual function normalizes, and the spermogram improves.
In macroprolactinomas, drug therapy is carried out under the control of tumor tomography in dynamics. If the size of the macroprolactinoma does not decrease against the background of taking medications, and the deterioration of vision progresses, the issue of surgical removal of the adenoma is resolved. Prolactinoma removal (adenomectomy) is performed through a transsphenoidal access – a micro-incision in the sinuses.
In some cases, radiation therapy is resorted to for the treatment of prolactinomas, which allows stopping taking medications. The effect of radiation therapy is gradual, fully manifests itself after a few years, so radiation is not used in young women planning pregnancy. A side effect of radiation therapy should be considered the development of pituitary insufficiency. In this case, the patient needs replacement therapy: glucocorticoids with the development of adrenal insufficiency, L-thyroxine – with thyroid insufficiency (development of hypothyroidism), sex hormones (testosterone for men and estrogen for women).
Prognosis and prevention
Prognostic data for prolactinoma are determined by the magnitude, hormonal activity and clinical course of the disease. Relapse of prolactinoma and resumption of hyperprolactinemia in the 5-year postoperative period occurs in 20-50% of patients. Postoperative improvement in macroprolactinomas is noted in only 10-30% of cases.
Drug therapy of prolactinoma is designed for a long time. With microprolactinomas, a break in treatment is arranged once every 2 years for several weeks. In some patients, the tumor disappears during this period. With macroprolactinomas, long-term drug treatment is carried out, since the progression of adenoma growth is possible with interruptions in treatment. Prognostically unfavorable malignant prolactinomas.
Since the etiology of the development of prolactin has not been determined, prevention provides, first of all, the prevention of tumor recurrence. Dispensary control is established for patients: computed tomography and an ophthalmologist’s examination are performed annually, the level of prolactin in the blood is determined twice a year.