Prolactinoma
Encyclopedia
A prolactinoma is a benign
tumor
(adenoma
) of the pituitary gland
that produces a hormone
called prolactin
. It is the most common type of pituitary tumor. Symptoms of prolactinoma are caused by too much prolactin in the blood (hyperprolactinemia) or by pressure of the tumor on surrounding tissues.
Prolactin stimulates the breast
to produce milk, and has many other functions such as regulation of mood. Hence prolactin levels are usually higher during pregnancy and after childbirth. After delivery of a baby, a mother's prolactin levels come down to normal a few weeks after breastfeeding is discontinued. Each time the milk is dispensed, prolactin levels rise; this process may cycle to maintain milk production. In males it is responsible for the sexual refractory period
after orgasm
and excess levels can lead to erectile dysfunction
.
Based on size, a prolactinoma can be classified as a microprolactinoma (<10 mm diameter) or macroprolactinoma (>10 mm diameter).
studies indicate that 6-25% of the U. S. population have small pituitary tumors. Forty percent of these pituitary tumors produce prolactin, but most are not considered clinically significant. Clinically significant pituitary tumors affect the health of approximately 14 out of 100,000 people. In nonselected surgical series, this tumor accounts for approximately 25-30% of all pituitary adenomas. Some growth hormone (GH)–producing tumors also co-secrete prolactin. Microprolactinomas are much more common than macroprolactinomas.
The majority of moderately raised prolactin levels (up to 5000mIU/L) are not due to microprolactinomas but other causes. The effects of some prescription drugs are the most common. Other causes are other pituitary tumours and normal pregnancy and breastfeeding. This is discussed more under Hyperprolactinaemia
.
The xenoestrogenic Chemical Bisphenol-A has been shown to lead to Hyperprolactinaemia and growth of prolactin-producing pituitary Cells. The increasing and prolonged exposure of Bisphenol-A from childhood on, may contribute to the growth of a Prolactionma.
Those that are caused by increased Prolactin levels are:
Those that are caused by mass effect are:
) or irregular menses or infertility
, and in men with impaired sexual function and, in rare cases, milk secretion. If prolactin is high, a doctor will test thyroid
function and ask first about other conditions and medications known to raise prolactin secretion. The doctor will also request a magnetic resonance imaging (MRI), which is the most sensitive test for detecting pituitary tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computed Tomography
(CT scan) also gives an image of the pituitary, but it is less sensitive than the MRI.
In addition to assessing the size of the pituitary tumor, doctors also look for damage to surrounding tissues, and perform tests to assess whether production of other pituitary hormones is normal. Depending on the size of the tumor, the doctor may request an eye exam with measurement of visual fields.
is the chemical that normally inhibits prolactin secretion, so doctors may treat prolactinoma with bromocriptine
, cabergoline
or Quinagolide drugs that act like dopamine
. This type of drug is called a dopamine agonist
. These drugs shrink the tumor and return prolactin levels to normal in approximately 80% of patients. Both have been approved by the Food and Drug Administration
for the treatment of hyperprolactinemia. Bromocriptine
is associated with side-effects such as nausea
and dizziness
and hypotension
in patients with already low blood pressure readings. To avoid these side-effects, it is important for bromocriptine treatment to start slowly.
Bromocriptine treatment should not be interrupted without consulting a qualified endocrinologist. Prolactin levels often rise again in most people when the drug is discontinued. In some, however, prolactin levels remain normal, so the doctor may suggest reducing or discontinuing treatment every two years on a trial basis. Recent studies have shown increased success in remission of prolactin levels after discontinuation, in patients having been treated for at least 2 years prior to cessation of bromocriptine treatment.
Cabergoline
is also associated with side-effects such as nausea
and dizziness
, but these may be less common and less severe than with bromocriptine. However, people with low blood pressure should use caution when starting cabergoline treatment, as the long half-life of the drug (4-7 days) may inadvertently affect their ability to keep their blood pressure within normal limits, creating intense discomfort, dizziness, and even fainting upon standing and walking until the single first dose clears from their system. As with bromocriptine therapy, side-effects may be avoided or minimized if treatment is started slowly. If a patient's prolactin level remains normal for 6 months, a doctor may consider stopping treatment. Cabergoline should not be interrupted without consulting a qualified endocrinologist.
treatment.
The results of surgery depend a great deal on tumor size and prolactin level. The higher the prolactin level the lower the chance of normalizing serum
prolactin. In the best medical centers, surgery corrects prolactin levels in 80% of patients with a serum prolactin less than 250 ng/ml. Even in patients with large tumors that cannot be completely removed, drug therapy may be able to return serum prolactin to the normal range after surgery. Depending on the size of the tumor and how much of it is removed, studies show that 20 to 50% will recur, usually within five years.
A woman with a prolactinoma should discuss her plans to conceive with her physician, so she can be carefully evaluated prior to becoming pregnant. This evaluation will include a magnetic resonance imaging (MRI) scan to assess the size of the tumor and an eye examination with measurement of visual fields. As soon as a patient is pregnant, her doctor will usually advise that she stop taking bromocriptine or cabergoline, the common treatments for prolactinoma. Most endocrinologists see patients every two months throughout the pregnancy. The patient should consult her endocrinologist promptly if she develops symptoms — in particular, headaches, visual changes, nausea, vomiting, excessive thirst or urination, or extreme lethargy. Bromocriptine or cabergoline treatment may be renewed and additional treatment may be required if the patient develops symptoms from growth of the tumor during pregnancy.
At one time, oral contraceptives were thought to contribute to the development of prolactinomas. However, this is no longer thought to be true. Patients with prolactinoma treated with bromocriptine or cabergoline may also take oral contraceptives. Likewise, post-menopausal estrogen replacement is safe in patients with prolactinoma treated with medical therapy or surgery.
production in women and reduced testosterone
production in men. Although estrogen/testosterone production may be restored after treatment for hyperprolactinemia, even a year or two without estrogen/testosterone can compromise bone strength, and patients should protect themselves from osteoporosis by increasing exercise and calcium
intake through diet or supplementation, and by avoiding smoking. Patients may want to have bone density measurements to assess the effect of estrogen/testosterone deficiency on bone density. They may also want to discuss testosterone/estrogen replacement therapy with their physician.
Macroprolactinomas often require more aggressive treatment otherwise they may continue to grow. There is no way to reliably predict the rate of growth, as it is different for every individual. Regular monitoring by a specialist to detect any major changes in the tumor is recommended.
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
(adenoma
Adenoma
An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...
) of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
that produces a hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
called prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
. It is the most common type of pituitary tumor. Symptoms of prolactinoma are caused by too much prolactin in the blood (hyperprolactinemia) or by pressure of the tumor on surrounding tissues.
Prolactin stimulates the breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
to produce milk, and has many other functions such as regulation of mood. Hence prolactin levels are usually higher during pregnancy and after childbirth. After delivery of a baby, a mother's prolactin levels come down to normal a few weeks after breastfeeding is discontinued. Each time the milk is dispensed, prolactin levels rise; this process may cycle to maintain milk production. In males it is responsible for the sexual refractory period
Refractory period
In physiology, a refractory period is a period of time during which an organ or cell is incapable of repeating a particular action, or the amount of time it takes for an excitable membrane to be ready for a second stimulus once it returns to its resting state following an excitation...
after orgasm
Orgasm
Orgasm is the peak of the plateau phase of the sexual response cycle, characterized by an intense sensation of pleasure...
and excess levels can lead to erectile dysfunction
Erectile dysfunction
Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
.
Based on size, a prolactinoma can be classified as a microprolactinoma (<10 mm diameter) or macroprolactinoma (>10 mm diameter).
Prevalence
AutopsyAutopsy
An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...
studies indicate that 6-25% of the U. S. population have small pituitary tumors. Forty percent of these pituitary tumors produce prolactin, but most are not considered clinically significant. Clinically significant pituitary tumors affect the health of approximately 14 out of 100,000 people. In nonselected surgical series, this tumor accounts for approximately 25-30% of all pituitary adenomas. Some growth hormone (GH)–producing tumors also co-secrete prolactin. Microprolactinomas are much more common than macroprolactinomas.
Causes
The cause of pituitary tumors remains unknown. It has been shown that stress can significantly raise prolactin levels, which should make stress a diagnostic differential, though it usually is not considered such. Most pituitary tumors are sporadic — they are not genetically passed from parents to offspring.The majority of moderately raised prolactin levels (up to 5000mIU/L) are not due to microprolactinomas but other causes. The effects of some prescription drugs are the most common. Other causes are other pituitary tumours and normal pregnancy and breastfeeding. This is discussed more under Hyperprolactinaemia
Hyperprolactinaemia
Hyperprolactinaemia or hyperprolactinemia is the presence of abnormally-high levels of prolactin in the blood. Normal levels are less than 500 mIU/L for women, and less than 450 mIU/L for men....
.
The xenoestrogenic Chemical Bisphenol-A has been shown to lead to Hyperprolactinaemia and growth of prolactin-producing pituitary Cells. The increasing and prolonged exposure of Bisphenol-A from childhood on, may contribute to the growth of a Prolactionma.
Symptoms
The Symptoms due to a Prolactinoma are broadly divided into those that are caused by Increased Prolactin Levels or Mass effect.Those that are caused by increased Prolactin levels are:
- Amenorrhea
- GalactorrheaGalactorrheaGalactorrhea or galactorrhoea is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing.Contemporary Maternal-Newborn Nursing Care defines galactorrhea as "nipple discharge." -Causes:...
(infrequent in men) - Loss of axillary and pubic hair
- HypogonadismHypogonadismHypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
, gynecomastiaGynecomastiaGynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
(in males)
Those that are caused by mass effect are:
- Bitemporal hemianopsiaBitemporal hemianopsiaBitemporal hemianopsia is the medical description of a type of partial blindness where vision is missing in the outer half of both the right and left visual field...
(due to pressure on optic chiasma) - VertigoVertigoVertigo is a form of dizziness.Vertigo may also refer to:* Vertigo , a 1958 film by Alfred Hitchcock**Vertigo , its soundtrack** Vertigo effect, or Dolly zoom, a special effect in film, named after the movie...
- Nausea, vomiting
Diagnosis
A doctor will test for prolactin blood levels in women with unexplained milk secretion (galactorrheaGalactorrhea
Galactorrhea or galactorrhoea is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing.Contemporary Maternal-Newborn Nursing Care defines galactorrhea as "nipple discharge." -Causes:...
) or irregular menses or infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
, and in men with impaired sexual function and, in rare cases, milk secretion. If prolactin is high, a doctor will test thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
function and ask first about other conditions and medications known to raise prolactin secretion. The doctor will also request a magnetic resonance imaging (MRI), which is the most sensitive test for detecting pituitary tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computed Tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT scan) also gives an image of the pituitary, but it is less sensitive than the MRI.
In addition to assessing the size of the pituitary tumor, doctors also look for damage to surrounding tissues, and perform tests to assess whether production of other pituitary hormones is normal. Depending on the size of the tumor, the doctor may request an eye exam with measurement of visual fields.
Treatments
The goal of treatment is to return prolactin secretion to normal, reduce tumor size, correct any visual abnormalities, and restore normal pituitary function. As mentioned above, the impact of stress should be ruled out before the diagnosis of prolactinoma is given. Exercise can significantly reduce stress and, thereby, prolactin levels. In the case of very large tumors, only partial reduction of the prolactin levels may be possible.Drugs
DopamineDopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
is the chemical that normally inhibits prolactin secretion, so doctors may treat prolactinoma with bromocriptine
Bromocriptine
Bromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
, cabergoline
Cabergoline
Cabergoline , an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph cells...
or Quinagolide drugs that act like dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
. This type of drug is called a dopamine agonist
Dopamine agonist
A dopamine agonist is a compound that activates dopamine receptors in the absence of dopamine. Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins, ultimately leading to changes in gene transcription.-Uses:...
. These drugs shrink the tumor and return prolactin levels to normal in approximately 80% of patients. Both have been approved by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
for the treatment of hyperprolactinemia. Bromocriptine
Bromocriptine
Bromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
is associated with side-effects such as nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
and hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
in patients with already low blood pressure readings. To avoid these side-effects, it is important for bromocriptine treatment to start slowly.
Bromocriptine treatment should not be interrupted without consulting a qualified endocrinologist. Prolactin levels often rise again in most people when the drug is discontinued. In some, however, prolactin levels remain normal, so the doctor may suggest reducing or discontinuing treatment every two years on a trial basis. Recent studies have shown increased success in remission of prolactin levels after discontinuation, in patients having been treated for at least 2 years prior to cessation of bromocriptine treatment.
Cabergoline
Cabergoline
Cabergoline , an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph cells...
is also associated with side-effects such as nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, but these may be less common and less severe than with bromocriptine. However, people with low blood pressure should use caution when starting cabergoline treatment, as the long half-life of the drug (4-7 days) may inadvertently affect their ability to keep their blood pressure within normal limits, creating intense discomfort, dizziness, and even fainting upon standing and walking until the single first dose clears from their system. As with bromocriptine therapy, side-effects may be avoided or minimized if treatment is started slowly. If a patient's prolactin level remains normal for 6 months, a doctor may consider stopping treatment. Cabergoline should not be interrupted without consulting a qualified endocrinologist.
Surgery
Surgery should be considered if medical therapy cannot be tolerated or if it fails to reduce prolactin levels, restore normal reproduction and pituitary function, and reduce tumor size. If medical therapy is only partially successful, this therapy should continue, possibly combined with surgery or radiationRadiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
treatment.
The results of surgery depend a great deal on tumor size and prolactin level. The higher the prolactin level the lower the chance of normalizing serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
prolactin. In the best medical centers, surgery corrects prolactin levels in 80% of patients with a serum prolactin less than 250 ng/ml. Even in patients with large tumors that cannot be completely removed, drug therapy may be able to return serum prolactin to the normal range after surgery. Depending on the size of the tumor and how much of it is removed, studies show that 20 to 50% will recur, usually within five years.
Pregnancy and Oral Contraceptives
If a woman has a small prolactinoma, there is no reason that she cannot conceive and have a normal pregnancy after successful medical therapy. The pituitary enlarges and prolactin production increases during normal pregnancy in women without pituitary disorders. Women with prolactin-secreting tumors may experience further pituitary enlargement and must be closely monitored during pregnancy. However, damage to the pituitary or eye nerves occurs in less than one percent of pregnant women with prolactinoma. In women with large tumors, the risk of damage to the pituitary or eye nerves is greater, and some doctors consider it as high as 25%. If a woman has completed a successful pregnancy, the chances of her completing further successful pregnancies are extremely high.A woman with a prolactinoma should discuss her plans to conceive with her physician, so she can be carefully evaluated prior to becoming pregnant. This evaluation will include a magnetic resonance imaging (MRI) scan to assess the size of the tumor and an eye examination with measurement of visual fields. As soon as a patient is pregnant, her doctor will usually advise that she stop taking bromocriptine or cabergoline, the common treatments for prolactinoma. Most endocrinologists see patients every two months throughout the pregnancy. The patient should consult her endocrinologist promptly if she develops symptoms — in particular, headaches, visual changes, nausea, vomiting, excessive thirst or urination, or extreme lethargy. Bromocriptine or cabergoline treatment may be renewed and additional treatment may be required if the patient develops symptoms from growth of the tumor during pregnancy.
At one time, oral contraceptives were thought to contribute to the development of prolactinomas. However, this is no longer thought to be true. Patients with prolactinoma treated with bromocriptine or cabergoline may also take oral contraceptives. Likewise, post-menopausal estrogen replacement is safe in patients with prolactinoma treated with medical therapy or surgery.
Osteoporosis Risk
Hyperprolactinemia can cause reduced estrogenEstrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
production in women and reduced testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
production in men. Although estrogen/testosterone production may be restored after treatment for hyperprolactinemia, even a year or two without estrogen/testosterone can compromise bone strength, and patients should protect themselves from osteoporosis by increasing exercise and calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
intake through diet or supplementation, and by avoiding smoking. Patients may want to have bone density measurements to assess the effect of estrogen/testosterone deficiency on bone density. They may also want to discuss testosterone/estrogen replacement therapy with their physician.
Prognosis
People with microprolactinoma generally have an excellent prognosis. In 95% of cases the tumor will not show any signs of growth after a 4 to 6 year period.Macroprolactinomas often require more aggressive treatment otherwise they may continue to grow. There is no way to reliably predict the rate of growth, as it is different for every individual. Regular monitoring by a specialist to detect any major changes in the tumor is recommended.