Prolactinoma is a an adenoma of the anterior lobe of the pituitary gland that produces prolactin. It is the most common type of pituitary gland adenomas and it is associated with hyperprolactinemia.
The pituitary gland (click here
for a video about pituitary gland) is a pea-sized endocrine gland which controls the release of hormones from other endocrine glands. Furthermore, some body tissues are directly affected by hormones of the pituitary (i.e. Growth hormone (GH), Adrenocorticotropic hormone (ACTH), Thyroid-stimulating hormone (TSH) and Prolactin).
Most of pituitary tumors are benign and some patients with this type of adenoma are never diagnosed during their lifetime. Of course as the tumor increases his size, hormone-releasing (RH) cells of the pituitary may be harmed and consequently the pituitary may diminish his activity (Hypopituitarism
Prolactinoma is one of these adenomas which can develop in a pituitary gland. Here it is a classification of prolactinoma,based on size:
When larger than 4 cm, pituitary tumours are termed “giant”. PRL-secreting adenomas often have a propensity to invade adjacent structures and such tumours are termed “invasive giant prolactinomas”( IGPs).
- Microprolactinomas (<10 mm)
- Macroprolactinomas (>10 mm)
.(A. Siddiqui, N. Chew, K. Miszkiel (Nov 2008), "Unusual invasion by a giant prolactinoma”
, Lysholm Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, Queen Square, London)
Anyway it seems that hormone level do not closely correlate with tumor size.
Up to now, the sources of many pituitary tumors, including prolactinomas, still remain largely unknown. Most of these tumors are sporadic, meaning they are not genetically passed from parents to their children. Some patients with prolactinomas have Multiple endocrine neoplasia type 1
(MEN 1). This is a inherited condition which involves tumors of the pituitary gland, parathyroid gland and pancreas. Of course this leads to the overproduction of hormones.
A small number of people without MEN
1 have a familial tendency to develop prolactinomas. Researches about the gene(s) responsible for such cases of prolactinoma are not yet finished.
Prolactin-secreting tumors (prolactinomas), the most frequently occurring pituitary tumor, have a frequency that varies with age and sex.
Beckers A. (2005), "The epidemiology of prolactinomas”
, Springer science + Business Media, Inc. Manufactured in The Netherlands )
Predisposing factors includes:
- Young age(20-50 years),not pediatric-adolescent age(prevalence of 100/million)
- Female sex(prolactinomas are more common in women than in men,female-to-male ratio is approximately 10:1)
- Multiple endocrine neoplasia type 1(MEN 1)
- Invasive giant prolactinomas (IGPs) constitute up to 2% of all pituitary adenomas, with a male predominance and a male/female ratio of 6.5/1
Symptomps of prolactinoma are due to either enlargement of the pituitary gland which compresses contiguous structures or prolactine high levels in the blood.
Although prolactinoma isn't life-threatening, it can impair your vision, cause infertility and produce other effects.
We have to distinguish between the two different sex.
- Galactorrhea . Inappropriate milk flow from the breast in a woman who is not pregnant or nursing
- Decreased libido
- Amenorrhea. Absence of menstrual period
- Infertility due to hypogonadism (Rolland R, Corbey RS. (1977),"Hyperprolactinemia and hypogonadism in the human female.", European Journal of Obstetrics & Gynecology and Reproductive Biology)
- Vision changes
- Breast tenderness
- Vaginal dryness
- Decreased libido
- Impotence. There seems to be a relation between PRL levels and refractory period following orgasm. Click Here (P. Haake et al. (April 2002)"Absence of orgasm-induced prolactin secretion in a healthy multi-orgasmic male subject",International Journal of Impotence Research ) for some studies that gives further evidence to this relationship.
- Vision changes
Since female's symptoms are easier to detect and to link to the prolactinoma diagnosis,men on average, have larger prolactinomas at their presentation then women.
If a doctor detects typical prolactinoma's symptoms, he will confirm his diagnosis with some tests:
If your prolactin blood levels are high, your doctor may suggest you to test thyroid function and whether levels of other hormones controlled by the pituitary are within the normale range. Furthermore, he will obviously inquire about other conditions known to raise prolactin levels (i.e. Pregnancy, so women will be asked to have a pregnancy test).
It is kindly suggested to consult an endocrinologist.
Due to the fact that prolactinoma in men is often without any symptoms for many years,the mean age at diagnosis is 10 years greater in men than in women( Ciccarelli A., Daly AF, Beckers A. (2005), "The epidemiology of prolactinomas”, Springer science + Business Media, Inc. Manufactured in The Netherlands ).
- Hypothyroidism. Low levels of thyroid hormone causes a high TRH state which is known to stimulate prolactin production. That's the reason why doctor should test thyroid functionality before diagnosing prolactinoma.
- Pregnancy. Obviously pregnancy increases prolactin levels for the nursing (after pregnancy PRL levels decrease rapidly in postpartum women who do not breast feed. In those who do breast feed, however, serum PRL levels remain elevated for the first few weeks, with sharp surges in prolactin secretion during suckling. Within a few months, PRL levels return to normal, despite continued lactation (thanks to suck reflex )
- Stress(J.L. Meyerhoff, M.A. Oleshanksy, E.H. Mougey (1988),"Psychologic Stress Increases Plasma Levels of
Prolactin, Cortisol, and POMC-Derived Peptides
in Man"). A high prolactin level could sometimes just be because of stress.
- Pituitary tumor.It causes headaches,vision problems,visual disturbances,amenorrhea,etc. due to the obvious same location).
- Acromegaly. In 90% of acromegaly patients, the cause is a pituitary adenoma. In some patients with acromegaly, prolactin may be cosecreted with growth hormone,so PRL high levels can be the confounding factors which lead the doctor to prolactinoma diagnosis.
- Cushing's Syndrome.In 70% of cushing patients, the cause is a pituitary adenoma(as for prolactionoma and acromegaly).
Prolactinoma are initially treated with medication
. This is usually successfull. If not, surgery
will be undergone. As for any treatment, the goal is to make symptoms go away. In this case we will use medication to restore normal pituitary functison, return prolactin secretion to normal, reduce tumor size and correct any kind of visual abnormalities cause by the prolactinoma.
Not everyone needs treatment for prolactinoma,that goes without saying. It depends on the severity of the symptoms.
Drugs that are used to treat prolactinoma act like dopamine
, the chemical in the brain that normally inhibits prolactin secretion (PIF,prolactin-inhibiting factor). There are two drugs which have been both approved by the Food and Drug Administration
for the treatment of hyperprolactinemia:
Being these drugs dopamine agonists, they are used in other pathologies which involve dopamine, such as Parkinson's disease.
(Brand name: Parlodel) is an ergoline derivative which has great effects in improving prolactinoma's symptoms. It has some side effects,but these can be mitigated simply by starting the treatment at a lower dose and gradually increasing it to find the best dose for the patient.Side effects include: nausea, dizziness, orthostatic hypotension, headaches and vomiting through stimulation of the brainstem vomiting centre.
On discontinuation of therapy, however, hyperprolactinemia usually recurs, and treatment may therefore need to be continued for years.
That's the reason why bromocriptine treatment should not be interrupted without consulting a qualified endocrinologist.
(Brand name: Dostinex) is an ergot derivative which has higher affinity for D2 receptor sites, less severe side effects, and more convenient dosing schedule than the older bromocriptine. As for Bromocriptine, Cabergoline should not be interrupted without consulting a qualified endocrinologist.
Little was known about cabergoline efficacy in the treatment of invasive giant prolactinoma until some doctors decided to investigate the efficacy and safety of cabergoline in 10 male patients with IGP . They found out that Cabergoline represents an effective and well-tolerated treatment for invasive giant prolactinoma.
Serum prolactin concentrations before and during cabergoline treatment in 10 men with invasive giant prolactinoma.
Most people respond well to these drugs. However, large prolactinomas are harder to treat.
As said before, if medication doesn't improve the patient's situation, the doctor may suggest to undergo surgery. If prolactinoma doesn't get better in spite of medications and surgery, radiotherapy will be done. It may be given in two form:
- Conventional radiation
- Gamma knife or stereotactic radiosurgery. A form of radiation therapy that focuses high-powered x-rays on a small area of the body.
- vision loss.If untreated,a prolactinoma can compress the optic nerve.
- Hypopituitarism .Again, if untreated, a prolactinoma can compress the pituitary gland causing dysfunction of other hormones controlled by the pituitary(such as thyroid hormones,growth hormone,etc.)
- Bone loss (Osteoporosis ). Prolactin high levels can reduce production of testosterone and estrogen,decreasing bone density and consequently increasing the risk of osteoporosis.
- Pregnancy complications. During pregnancy,women's pituitary gland gets bigger( that is because lactotropic cells are producing prolactin, whose blood level increases). If a woman has already an enlarged prolactinoma, she will experience additional pituitary growth along with changes in vision and headaches.
7.CASE REPORT 1
Unusual orbital invasion by a giant prolactinoma.(A. Siddiqui, N. Chew, K. Miszkiel (Nov 2008), "Unusual invasion by a giant prolactinoma”, Lysholm Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, Queen Square, London)
38-year-old man with the following symptoms:
- gradual right-sided retro-orbital pain
While awaiting referral to outpatient neurology, he also experienced episodes of déjà vu sensation and developed left-sided pyramidal symptoms.
Axial post-contrast CT image shows an enhancing mass in the pituitary fossa. Note the bulky right parasellar component and the tubular structure within the right orbit, appearing like an enlarged superior ophthalmic vein (arrow).
Coronal short tau inversion-recovery MRI shows hyperintense tumour tissue within the right orbit (arrow) interposed between the optic nerve and superior rectus muscle.
On biochemistry, the initial serum prolactin (PRL) level was massively elevated, with a value of just over 900 000 mIU l–1.
Serum PRL levels and MRI images lead doctors to the diagnosis of an invasive giant prolacinoma (IGP) and consequently treatment with cabergoline was started.
Six months after treatment, follow-up imaging showed moderate shrinkage of the tumour with a partial improvement in visual fields, and was accompanied by a drop in serum PRL to 66 000 mIU l–1 over 18 months.
Orbital extension with intraconal involvement by a pituitary adenoma is an extremely unusual occurrence, but of course radiologist must not forget this possibility (especially if patient has a prolactinoma presenting with unilateral proptosis). This case report showed us also the importance and the sensibility of MRI in comparison with CT scan.
8.CASE REPORT 2
A case of prolactinoma with galactorrhea in man.(Inoue T., Nakagaki H. et al. (May 1984), "Unusual invasion by a giant prolactinoma”,No Shinkei Geka)
28-year-old man with the following symptoms:
- severe headache
- nausea and vomiting
- decreased libido
On admission, he showed:
- normal pubic and axillary hairs
- normal development of the external genital organs
- decreased movement of sperma
- negative ophthalmologic examination
- Hyperprolactinemia (prolactin 697 ng/ml,suppressed by bromocriptine and L-DOPA loading test.)
- Serum testosterone level 282 ng/dl(Male: 300 -1,200 ng/dL)
- CT scan showed an isodensity mass in and above the sella
The diagnosis of prolactinoma was made, and a radical removal of the tumor was done through the transsphenoidal route.
After the surgery:
- Serum prolactin level decreased to 150 ng/ml and finally returned to normal by administration of 2.5 mg of bromocriptine.
- Serum testosterone level was slightly elevated.
- The movement of the sperma showed no improvement.
- No postoperative complications such as hypopituitarism and CSF rhinorrhea