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Prolactinomas, the most common type of pituitary adenomas, cause excess secretion of the hormone prolactin (PRL). Physiologically, prolactin is a hormone that stimulates breast milk production in pregnant and nursing women and its level falls with cessation of breast feeding. Very high levels of prolactin (hyperprolactinemia) can cause hormonal disturbances including milk production to occur in men as well as in non- pregnant women.


Prolactinomas account for approximately 30% of all pituitary adenomas. Some growth hormone (GH)-producing tumors also co-secrete prolactin. Prolactinomas come in various sizes, but the majority are microprolactinomas (less than 10mm in diameter). The incidence of prolactinomas is higher in women than in men (this may be due, in part, to the fact that men with this tumor may present much later for clinical evaluation of subtle complaints of hypogonadism e.g. erectile dysfunction (impotence), compared to women who often present earlier for clinical evaluation of amenorrhea). Prolactinomas occur most commonly in the third and fourth decades of life.

Prolactinomas cause symptoms either due to the hormonal effects of excess PRL or due to the space-occupying effects and the pressure which they exert on the pituitary gland and the critical neurovascular structures that surround it such as the optic nerves. The hormonal symptoms resulting from hyperprolactinemia are different in males than in females.

Prolactinomas, are the most common cause of hyperprolactinemia, but there are several other causes of hyperprolactinemia that most importantly include the use of certain "anti-dopaminergic" medications (prolactin secretion from the pituitary gland is normally suppressed by the brain chemical, "dopamine"), these include Metoclopramide (Reglan), or anti-depressants such as Fluoxetine (Prozac), an underactive thyroid gland (hypothyroidism), and other types of pituitary tumors that arise in or near the pituitary gland- as those may compress the pituitary stalk and block the flow of dopamine from the brain to the prolactin-secreting cells causing hyperprolactinemia, this is commonly known as "stalk effect".

Prolactin is a hormone that physiologically induces lactation or milk production. In women, a high blood level of prolactin can cause reduced estrogen production that often leads to infertility and changes in menstruation. In some women, menstrual periods may disappear altogether, while in others, periods may become irregular or menstrual flow may change. Women who are not pregnant or nursing may begin producing breast milk. Some women may experience a loss of libido and intercourse may become painful because of vaginal dryness.

In men, hyperprolactinemia can cause reduced testosterone production and the most common symptoms of prolactinomas in men are erectile dysfunction, decreased libido, enlargement of breast tissue (gynecomastia), and infertility. As men have no reliable indicator such as menstruation to signal a problem, many men delay going to the doctor until they have headaches or eye problems caused by the prolactinoma and they may not notice the gradual decrease of sexual function or libido.

Hormonal symptoms also vary with age and postmenopausal women and elderly men frequently present only with the space-occupying effects of the tumor. Also, if a prolactinoma develops prepubertally, hyperprolactinemia may result in a female body habitus and small testicles. If the prolactinoma is large enough to compress the surrounding normal hormone-secreting pituitary cells, it may result in deficiencies of one or more of the pituitary hormones e.g. thyroid-stimulating hormone (TSH), GH, and adrenocorticotropic hormone (ACTH).

The amount of prolactin that a prolactinoma secretes has a good correlation with its size. In addition, larger tumors are frequently associated with headache due to stretching of the pain-sensitive structures around the pituitary gland. Encroachment on surrounding neurovascular structures may result in visual problems in the form of field defects, ranging from bitemporal hemianopia (from compression of the optic chiasm), which is common, to total loss of vision and ophthalmoplegia (from compression of cranial nerves III, IV, or VI within the cavernous sinuses).

A thorough medical history and neurological examination focused on assessing the presence of clinical manifestations of hyperprolactinemia, such as galactorrhea (spontaneous flow of milk from the breasts unassociated with childbirth or nursing) and on identification of clinical signs of estrogen deficiency. In men, the focus is on clinical signs of testosterone deficiency such as testicular size and the consistency and pattern of body hair as well as the rare occurrence of gynecomastia, galactorrhea, or both.

If blood tests confirm a raised prolactin level, a further blood sample is taken to make sure that the thyroid gland is functioning normally (hyperproactinemia may be due to hypothyroidism). Sex hormones and other hormones produced by the pituitary gland will also need to be checked.

A scan of the pituitary hypothalamic area is then performed to show the size, location and characteristics of the Prolactinoma and to give detailed pictures of the pituitary gland. There are two types of scans: computerized tomography (CT) and magnetic resonance imaging (MRI), both performed with and without intravenous contrast. MRI is superior to CT in soft tissue delineation and identification of a small pituitary lesion, while CT scan is better for identification of any bone distortion or destruction resulting from pressure or direct bone invasion by the tumor. Dynamic MRI of the pituitary is a relatively new technique that has gained importance in the evaluation of pituitary adenomas, especially microadenomas as it can detect them and differentiate them from the normal pituitary gland.

Neuroopthalmological assessment of visual acuity (VA) and visual fields (VF) is performed when the tumor is large and is in close vicinity of the optic nerves or chiasm, and when visual symptoms are present as well as to obtain a "baseline" for vision prior to any therapy.

Treatment is indicated if mass effects from the tumor, significant effects from hyperprolactinemia, or both are present. The goal of treatment is to return prolactin secretion to normal, reduce tumor size, correct any visual abnormalities, and restore normal pituitary function. Treatment options include medical, surgical and pituitary irradiation.

In Prolactinoma patients with minimal symptoms or no symptoms, the patient can be monitored closely with serial estimations of serum PRL levels combined with imaging studies at yearly intervals.

As dopamine is the chemical that normally inhibits prolactin secretion by the pituitary gland, drugs that act like dopamine or dopamine agonists e.g. Bromocriptine (Parlodel), pergolide (Permax), and cabergoline (Dostinex) are used in the treatment of prolactinomas. Once started, these drugs must be continued for life as prolactin levels often rise again in most people when the drug is discontinued and failure is more likely with large prolactinomas. Using bromocriptine or one of the other drugs over time can reduce the chance of a cure using surgical removal. Therefore, if surgery is to be performed, its best timing is during the first six months of using medical therapy.

Surgical treatment is reserved for women who have a microaprolactinoma, desire pregnancy and cannot tolerate or do not wish to take bromocriptine or one of the other drugs, patients who do not respond to medical treatment, or those who show progression of symptoms after an initial response to medical treatment.

The use of radiotherapy for prolactinomas has declined in recent years due to the remarkable effectiveness of other treatments such as medications and surgery, hence it is usually reserved for patients who have persistent and progressive symptoms that were not cured by medications or surgery, or patients who cannot tolerate them.

If untreated, prolactinomas may enlarge, producing mass effects such as visual deficits or total blindness, cranial nerve palsies, hydrocephalus, pituitary apoplexy, and hypopituitarism. The effects of prolonged untreated hyperprolactinemia can include hypogonadism, infertility and osteoporosis.

In women, once prolactin has fallen to normal, menstrual cycles usually resume and fertility is restored in most cases. In men, testosterone levels may rise, which brings improvement in their sexual lives. However, the higher the prolactin level, the lower the chance of normalizing it, and therefore, early detection is "key" for successful treatment. In the case of very large tumors, only partial achievement of the treatment goals may be possible, but in this case "remission" of the tumor with low levels of prolactin, or a healthy patient with minimal or no symptoms or signs can still be defined as cure.

Even with successful treatment, careful monitoring of clinical signs and symptoms, serial measurements of serum PRL levels and pituitary imaging on yearly basis for the rest of the follow-up period are essential.

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