Generality
Prolactinoma is a benign tumor of the anterior pituitary, which, when large, promotes the production of prolactin so strongly that it establishes a medical condition known as hyperprolactinemia.
In women, prolactinoma is mainly responsible for: oligomenorrhea, amenorrhea, galactorrhoea, acne and hirsutism; in men, however, it causes: gynecomastia, erectile dysfunction and hair loss. Furthermore - but this applies to both sexes - its presence reduces sexual desire and can cause disorders such as: headache, vomiting, nausea, hypopituitarism and bitemporal hemianopia.
Due to still unknown triggers, prolactinoma requires treatment only when it is responsible for the symptoms and signs shown above. Practical treatments include both pharmacological remedies and surgical remedies.
Short recall on prolactin
Prolactin is a hormone, whose secretion belongs to the pituitary gland, to be precise to the anterior pituitary or adenohypophysis .
Prolactin is known to most people mainly because of its crucial role in women; in fact, in women, it promotes:
- Breast development in puberty e
- The lactation process in the postpartum phase.
As far as man is concerned, the role of prolactin is much less clear and definite than in women. The only certainties in this regard are that, with prolactin hyperproduction in males, there are problems such as: erectile dysfunction, gynecomastia (or abnormal development of the breast in humans) and impotence (linked to an inhibitory action against testosterone).
What is Prolactinoma?
Prolactinoma is a benign tumor of the pituitary gland, which causes a hyperproduction of the hormone prolactin and consequently establishes a condition of hyperprolactinemia (high blood prolactin).
Although it is not a deadly tumor, prolactinoma can have unpleasant consequences, starting from the conspicuous reduction of sex hormone levels, both in women (estrogens) and in men (testosterone).
What kind of benign tumor is it?
Prolactinoma is a benign tumor belonging to the type of adenomas .
In the medical field, any benign tumor that derives from epithelial cells of the exocrine glandular organs or from epithelial cells of tissues with secretory properties is called adenoma.
Epidemiology
Among pituitary tumors with the peculiarity of stimulating hormonal secretion (in this case the prolactin secretion), prolactinoma is the most common.
Statistics show that prolactinoma is a widespread tumor in the general population, but also that it is clinically relevant only in a small number of cases (14 individuals per 100, 000).
Quite unusual among young people, prolactinoma occurs more frequently in women than in men.
Curiosity
Autopsy studies conducted in the United States have shown that between 6 and 25% of the US population is the carrier of a small prolactinoma, which is irrelevant from a clinical point of view.
Causes
Currently, the causes of prolactinoma are unknown; however, studies conducted on the subject have not been completely useless, as they have shown that:
- Prolactinoma is a sporadic tumor, therefore it is not transmitted by inheritance.
- Prolonged exposure to bisphenol A xenoestrogen promotes the growth and activity of pituitary cells that produce prolactin ( lactotropic cells ), promoting hyperprolactinemia.
Symptoms and Complications
If it is small, prolactinoma is a generally asymptomatic presence, ie without symptoms and signs; in these situations, therefore, the affected person is well and leads a completely normal life.
On the contrary, if the prolactinoma is of medium-large size, it is responsible for a very precise symptomatology, which is explained by hyperprolactinemia - a condition deriving from the greater production of prolactin - and in the compression exerted by the tumor mass, with respect to anatomical structures adjacent.
Consequences of hyperprolactinemia in women
In women, prolactinoma-induced hyperprolactinaemia may be due to:
- A delay in the recurrence of menstruation ( oligomenorrhea ) or the absence of menstruation ( amenorrhea );
- Galactorrhea, or the release of milk from the breasts outside the period of breastfeeding;
- Dyspareunia, ie pain during sexual intercourse;
- Acne and hirsutism (abnormal growth of hard and coarse hair in female people).
Consequence of hyperprolactinemia in humans
In men, hyperprolactinaemia resulting from a prolactinoma can determine:
- Erectile dysfunction ;
- Reduction of hair on the face and in general on the whole body;
- Gynecomastia, or abnormal development of the breasts;
- Male galactorrhea (very rare).
Consequences of hyperprolactinemia common to both sexes
In both men and women, prolactinoma-dependent hyperprolactinemia is responsible for:
- Hypogonadism . It is the reduction of functional activity of the gonads, which leads to a drop in testosterone levels, in men, and to a drop in estrogen levels, in women.
- A decrease in sexual desire (or decrease in libido ). It is a consequence of the reduction of testosterone, in men, and of estrogens, in women.
- A decrease in bone mineral density . For both sexes, the cause of this decline is, once again, the reduction of circulating sex hormones.
- Infertility .
Consequences of the mass effect
The compression exerted by a medium-large prolactinoma of neighboring structures can give rise to:
- Recurrent headache;
- Dizziness;
- Nausea and vomit;
- Bitemporal hemianopsia. It is an alteration of vision characterized by the impossibility of perceiving a half of the visual field.
It may arise from a prolactinoma, when the tumor in question comes into contact with the optic chiasm, a characteristic area of the brain adjacent to the pituitary gland, where the nerve fibers of the optic nerves cross;
- Reduction of other pituitary hormones (hypopituitarism). It is as if, due to its considerable volume, the prolactinoma prevents the other pituitary cells from functioning properly.
Complications
Possible complications attributable to prolactinoma are:
- Osteoporosis . It depends on the decrease in bone mineral density, a drop that, as previously described, derives from the increase in prolactin in the blood and the consequent reduction of sex hormones.
- Hypothyroidism, adrenal insufficiency and growth hormone deficiency . These are all conditions that depend on prolonged hypopituitarism.
Curiosity: consequence of a pregnancy in the presence of prolactinoma
In women with a small and asymptomatic prolactinoma, the state of pregnancy (due to the greater amount of circulating estrogen) can promote the enlargement of the tumor mass and its manifestation through symptoms, such as headache, dizziness, vision problems, etc.
THE PROLACTINOMA CAN CHANGE IN TIME?
Medical studies have observed that prolactinoma has a different growth rate from individual to individual, but also that when it is small, it tends to remain so, whereas when it is medium-large it has a greater tendency to become even larger.
In any case, however, the prolactinoma hardly assumes a malignant nature, transforming itself from an adenoma to an adenocarcinoma.
When should I go to the doctor?
Symptoms and signs, such as oligomenorrhea, amenorrhea, galactorrhea, erectile dysfunction, gynecomastia, hirsutism, etc., always have a certain clinical relevance, therefore, in their presence, it is advisable to contact without hesitation and at most soon the treating doctor.
Diagnosis
In general, the diagnosis of prolactinoma starts from the physical examination and from the anamnesis; therefore, it continues with in-depth blood tests and a diagnostic imaging test (nuclear magnetic resonance or CT scan) related to the brain; finally, it ends with an examination of sight.
Physical examination and medical history
Physical examination and medical history help the doctor to know the present symptoms in detail. The knowledge of the symptoms and the signs in progress is fundamental to outline a hypothetical clinical picture and establish with which other investigations to continue.
Blood tests
Blood tests allow us to estimate prolactin levels.
As stated on more than one occasion, hyperprolactinemia (ie the high concentration of prolactin in the blood) is a typical consequence of prolactinoma.
MRI or CT scan to the brain
Nuclear magnetic resonance and the CT scan of the brain are the only diagnostic tests that confirm the presence of a prolactinoma, a presence that until now was only a hypothesis.
Causes of hyperprolactinemia that could be mistaken for prolactinoma
The presence of hyperprolactinemia does not automatically mean prolactinoma. This explains why, after a blood test that shows high levels of prolactin, it is advisable to carry out an assessment using either an MRI scan of the brain or a brain CT scan.
The causes of hyperprolactinaemia different from prolactinoma include: hypothyroidism, the intake of certain drugs (eg: dopamin antagonists, inhibitors of dopamine synthesis, serotonin reuptake inhibitors), chronic renal failure, cirrhosis, the stress, pituitary tumors other than prolactinoma (eg: craniopharyngioma) etc.
Therapy
The objectives of the therapy adopted in the presence of a prolactinoma are:
- Bring the blood levels of prolactin back to normal;
- Restore normal pituitary functions;
- Reduce the size of the tumor mass, so as to eliminate the symptoms deriving from the compression of adjacent anatomical structures;
- Improve the patient's quality of life in general.
Currently, in order to achieve these goals, patients with symptomatic prolactinoma can rely on both drug therapy and surgical therapy; the details relating to these two possible therapies will be discussed in the next two paragraphs.
Pharmacological therapy
To understand the pharmacological therapy of prolactinoma, it is necessary to take a small step back and inform the reader that dopamine - the known neurotransmitter associated with Parkinson's disease and addiction to many drugs - plays the important role of physiological inhibitor of the secretion of prolactin; in other words, in a healthy person, to stop the production of prolactin (to avoid an excess of it in the blood) is dopamine.
Returning therefore to the pharmacological therapy of prolactinoma, this treatment consists substantially in the administration of dopaminergic agonists, that is to say medicines that mimic, once assumed, the effects of dopamine against the secretion of prolactin by the pituitary gland.
It should be pointed out that among the dopaminergic agonists used in the treatment of prolactinoma, bromocriptine and cabergoline stand out, due to their additional ability to reduce the size of the tumor mass. In other words, bromocriptine and cabergoline perform not only the same inhibitory action as dopamine (against pituitary cells that produce prolactin), but are also able to regulate prolactinoma .
Acting mainly on symptoms, prolactinoma drug therapy is a treatment that patients must undergo for a long time, if not for the rest of their lives.
HOW EFFICIENT IS PHARMACOLOGICAL THERAPY?
Statistics show that the use of bromocriptine and cabergoline, in people with prolactinoma, reduces the tumor mass and returns too high levels of prolactinoma in up to 80% of clinical cases.
Thus, bromocriptine and cabergoline are excellent drugs for the treatment of prolactinoma, so much so as to constitute the first line treatment for this type of tumor.
SIDE EFFECTS OF BROMOCRIPTINA AND CABERGOLINA
Taking bromocriptine or cabergoline may have adverse effects, such as: nausea, vomiting, dizziness, headache and drowsiness.
These side effects are most frequently developed in patients with prolactinoma who also suffer from hypotension or who have physiologically low blood pressure.
In general, however, anti-prolactinoma drugs are considered quite safe.
Curiosity
In very rare circumstances, cabergoline can damage heart valves or lead to the development of abnormal behavior, such as the tendency to gambling.
BROMOCRIPTINA AND CABERGOLINA DURING PREGNANCY
Currently, the effects of taking bromocriptine or cabergoline during pregnancy are unclear.
Therefore, once pregnant, women with a prolactinoma, who are following a therapy based on one of the drugs in question, are forced to stop hiring (unless otherwise indicated by the doctor).
IS BROMOCRIPTINA OR CABERGOLINA BETTER?
- Cabergoline appears to be more effective than bromocriptine; moreover, it is less frequently the cause of side effects.
- Bromocriptine, however, is less expensive than cabergoline and is widely safe in the event of prolonged use (the long-term consequences of using cabergoline are not yet clear).
Surgical therapy
Prolactinoma surgical therapy consists of an operation to remove the tumor mass.
Given the delicacy of this operation, doctors resort to surgery only if drug therapy has proved ineffective (in other words, therefore, when there are no alternatives).
Currently, two surgical techniques (or surgical approaches) are available for excision surgery : so-called transsphenoidal surgery and so-called transcranial surgery .
Ideal for small prolactinomas, transsphenoidal surgery involves removing the tumor mass through the nasal cavities; specific for large prolactinomas, on the other hand, transcranial surgery involves removing the tumor mass through an incision made in the skull.
If practiced properly, prolactinoma surgical therapy is very effective; however, it should be pointed out that, even in the case of successful surgery, it can happen that the prolactinoma reappears after some time (recurrence).
When does surgical therapy replace drug therapy during prolactinoma?
- When, despite pharmacological recruitment, prolactin levels remain high.
- When prolactinomas are very large and drugs, despite reducing circulating prolactin, fail to appreciably reduce the size of the tumor mass (hence, prolactinoma continues to press on adjacent brain structures).
WHO IS THE CHOICE OF THE SURGICAL APPROACH
The choice of the surgical approach is left to the specialist doctor who will carry out the future removal of the prolactinoma.
Every decision concerning the surgical removal technique comes after an appropriate assessment of the size of the tumor mass and its precise position.
Prognosis
The prognosis in the case of prolactinoma varies from excellent, when the tumor mass is small, to variable, when the tumor mass is medium-large. In the first circumstance, in fact, the prolactinoma is asymptomatic and hardly increases in volume over time, while, in the second circumstance, it is responsible for disorders that may not respond to the therapies adopted and could expand further, causing new symptoms (and worsening those already present).
A medium to large prolactinoma requires the planning of an adequate pharmacological treatment, which, in case of failure, forces to resort to surgery.
Importance of monitoring
Doctors recommend that those who carry prolactinoma have periodic monitoring of the prolactinoma, to detect changes in time.
