Prolactinoma: Types, Symptoms, Causes, Complications, Diagnosis and Treatment


Prolactinoma is a condition caused by overproduction of the hormone prolactinin by a noncancerous tumor or adenoma of the pituitary gland in your brain.

June 12, 2018

Prolactinoma is a condition caused by overproduction of the hormone prolactinin by a noncancerous tumor or adenoma of the pituitary gland in your brain. Prolactinoma is the most common type of hormone-producing tumor that can develop in your pituitary gland. The major effect is decreased levels of sex hormones estrogen in women and testosterone in men.
Although it isn't life-threatening, it can impair your vision, cause infertility and produce other effects. Most prolactinomas occur sporadically and the risk of recurrence in the family is very low. However, prolactinomas those are due to a genetic predisposition carry a high risk of recurrence. The aims of treatment is to reduce the overproduction of prolactin level to normal, reduce the tumor size, and restore the normal pituitary function.
Pituitary gland is the master gland that plays a critical role in regulating growth and development, metabolism, and reproduction in our body. This gland produces prolactin and a number of other key hormones including:

  • Growth hormone, which regulates growth
  • ACTH or adrenocorticotropin hormone which stimulates the adrenal glands to produce cortisol, especially during stressful events such as surgery, trauma etc.
  • Thyroid stimulating hormone (TSH), which signals the thyroid gland to produce thyroid hormone
  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which regulate ovulation and estrogen and progesterone production in women, and sperm formation and testosterone production in men.

A prolactinoma is a benign tumor of the pituitary gland that produces an excessive amount of the hormone prolactin. Prolactin is a natural hormone which supports normal lactation of a woman. Lactation is the secretion of milk by the mammary glands of the breast. Prolactin stimulates the breast tissues to enlarge during pregnancy. The prolactin level of a mother falls after delivery of the baby unless she breastfeeds her infant. Each time the baby nurses from the breasts, prolactin levels rise to maintain milk production.
Prolactinomas are the most common type of pituitary tumor. The excessive release of prolactin from the tumor into the blood causes pressure of the tumor on surrounding tissues resulting in a condition known as hyperprolactinemia. Most prolactinomas occur in women between 20 and 34 years old. However, it can occur in both sexes at any age. The disorder is rare in children.

Types of Prolactinomas:

Prolactinomas are usually classified into 2 groups. These include microadenomas which are less than 1 cm while macroadenomas are above 8mm. The size may play a role in symptoms caused by local compression, and are considered for determining the choice of treatment.

Symptoms of Prolactinomas:

Signs and symptoms can result from excessive prolactin in your blood or from pressure on surrounding tissues from a large tumor. Some of the signs and symptoms of prolactinoma are specific to females or males as elevated prolactin can disrupt the reproductive system.
Most women with prolactinomas are likely to have microprolactinomas.

Prolactinoma in females can cause:

  • Irregular menstrual periods called oligomenorrhea or no menstrual periods known as amenorrhea as excessive prolactin interferes with the pituitary's production of the hormones FSH and LH which control the menstrual cycle.   
  • Milky discharge from the breasts called as galactorrhea even if you are not pregnant or breast-feeding
  • Painful intercourse due to vaginal dryness
  • Acne and excessive body and facial hair growth known as hirsutism
  • infertility because of impaired egg release by the ovaries

Women with prolactinomas do not have any increased risk of breast cancer.
Men with prolactinomas usually have macroprolactinomas where the tumours are larger than 10mm in diameter.

Prolactinoma in males can cause:

  • Erectile dysfunction
  • Decreased body and facial hair
  • Uncommonly, enlarged breasts called as gynecomastia
  • infertility due to a low sperm count
  • Milk production by the male breast can occur but is very uncommon even when prolactin levels are very high.

Prolactinoma in both sexes can cause:

  • Low bone density
  • Reduction of other hormone production by the pituitary gland as a result of tumor pressure
  • Loss of interest in sexual activity or low libido
  • Headaches
  • Visual disturbances
  • Infertility

Women are more likely to notice signs and symptoms earlier than men, when tumors are smaller in size, probably because they are alerted by missed or irregular menstrual periods. Men tend to notice signs and symptoms later, when tumors are larger. Enlargement of the pituitary gland can also cause local symptoms such as headache or vision problems.

Causes of Prolactinomas:

The sources of many pituitary tumors, including prolactinomas is unknown.
Most pituitary tumors appear sporadically which means that no one else in the family has had a pituitary tumor.
A genetic disorder called multiple endocrine neoplasia type I (MEN1) may be responsible for prolactinomas in some patients. MEN1 is an inherited condition characterized by a high frequency of peptic ulcer disease and abnormal hormone production from the pancreas, parathyroid, and pituitary glands. Prolactinomas are a characteristic feature of MEN1. A small number of people have a familial tendency to develop prolactinomas but do not appear to have MEN1.
The main cause is raise in the level of prolactin which may be due to

  • Pregnancy and breast-feeding
  • Nipple stimulation and suckling
  • Stress

Certain medications that include:

  • Anti sickness medications such as Metoclopramide, stemetil, Domperidone, also acid reducing medication like Omeprazole can raise your prolactin level.
  • Certain antidepressants and tranquillisers used to treat mental health illness can raise prolactin. Examples include Amytriptyline and Fluoxetine and risperidone.
  • Some homeopathic and herbal medications.

Another possibility of raised prolactin is an underactive thyroid gland, which can be diagnosed by a simple blood test and which requires treatment with thyroid hormone tablets. The possibility of a prolactinoma will be consider once these causes are excluded.

Complications of Prolactinomas:

Complications of prolactinoma may include:

Vision loss:

Left untreated, a prolactinoma may grow large enough to compress your optic nerve.

Hypopituitarism:

With larger prolactinomas, pressure on the normal pituitary gland can cause dysfunction of other hormones controlled by the pituitary, resulting in hypothyroidism, adrenal insufficiency and growth hormone deficiency.

Bone loss or osteoporosis:

Too much prolactin can reduce production of the hormones estrogen and testosterone, resulting in decreased bone density and an increased risk of osteoporosis.

Pregnancy complications:

During a normal pregnancy, the production of estrogen increases. If you are pregnant and have a large prolactinoma, these high levels of estrogen may cause tumor growth and associated signs and symptoms, such as headaches and changes in vision.
If you have prolactinoma and you want to become or are already pregnant, adjustments in your treatment and monitoring may be necessary. Speak to your doctor in this situation.

Diagnosis of Prolactinomas:

The tests to diagnose a prolactinoma consist of blood tests to check hormone levels and a scan of the pituitary gland to show the size of the prolactinoma. Blood tests can detect the overproduction of prolactin. The test is also done to determine if the levels of other hormones controlled by the pituitary are within the normal range. Women of childbearing age also will have a pregnancy test.
Thyroid function will usually be checked if the prolactin level is high. Questions will be asked about conditions and medications you are taking to know the cause of raised prolactin secretion.
Magnetic resonance imaging (MRI) is the most sensitive test for detecting and measuring prolactinomas. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computer tomography (CT scan) also provides an image of the pituitary, but it is less sensitive than the MRI for detection of a prolactinoma.
A vision test will be done if you have any problems with your vision. Probably you will be seen by an eye specialist called opthalmologist who will check the strength of your eyesight and chart your fields of vision and conclude if if a pituitary tumor has impaired your sight.
At times a DEXA scan is recommended in which an X-ray scan of your spine and hip bones will be done to see whether there is any evidence of thinning of the bones or osteoporosis.
Women who have not had periods for a year, and male patients with prolonged low testosterone levels are often recommended for a bone density tests to ensure that they are not developing osteoporosis.

Treatment of Prolactinomas:

The aim of treatment is to:

  • Return the production of prolactin to normal levels
  • Restore normal pituitary gland function
  • Reduce the size of the pituitary tumor
  • Eliminate any signs or symptoms from tumor pressure, such as headaches or vision problems
  • Improve quality of life

The treatment of prolactinoma can be done either by medications or surgery.

Medications for prolactinoma:

Oral medications such as dopamine agonists are often the choice of treatment which can decrease the production of prolactin and eliminate symptoms. Medications may also shrink the tumor. However, long-term treatment with medications is generally necessary.
These drugs mimic the effects of dopamine, but are much more potent and long lasting. Dopamine is the brain chemical that normally controls prolactin production. Commonly prescribed medications include bromocriptine, quinagolide and cabergoline. These drugs decrease prolactin production and may shrink the tumor in most people with prolactinoma.

  • Cabergoline is long acting and requires one or two doses per week. The usual dose of cabergoline is one tablet of 0.5mg once or twice a week, although higher doses are occasionally required. Sometimes the dose can be reduced later during long-term treatment.
  • Bromocriptine is usually given twice or three times daily. The prescribed dose is one tablet of 2.5mg.
  • Quinagolide is taken once daily, with the dose increased gradually to 75micrograms.

These drugs are safe and well tolerated by most patients. These drugs should be taken with food to minimize any side effects, particularly dizziness on standing up, nausea and headaches. Cabergoline should to be taken at night when going to bed with a light supper or snack such as tea/milk and a biscuit. This should reduce the chance of any unwanted effects.
Also these drugs should start with a very low dose of medication which can be gradually increased to reduce the side effects. Generally these side effects will diminish as your body becomes used to the medication. But in case they persist or become unbearable, discuss with your consultant. Occasionally, the medications may cause slight constipation which can usually be cured by increasing the amount of fiber in your diet. Tiredness, abdominal pain, breast discomfort and nasal congestion are some of the other side effects of these medication. Psychological disturbance may be a rare complication of either cabergoline or bromocriptine.
Cabergoline appears to be more effective than bromocriptine. It also has less frequent and less severe side effects. However, it is more expensive than bromocriptine.
Patients with Parkinson's disease using dopamine agonists in large doses, often at least 20 times those used for prolactinoma treatment will have risk associated with some heart valve problems. However, this is not the case in patients with prolactinoma on the lower doses of cabergoline which are generally used in this condition. Patients taking Cabergoline or Bromocriptine for pituitary conditions will be advised to have occasional echocardiograms as a precaution. Generally within a few weeks of starting the treatment, prolactin levels fall to normal. Once prolactin comes to normal level, menstrual cycles usually resume, interest in sex is regained and fertility is restored in most cases of a women. In men, testosterone levels may raise, which often improves sex drive and potency.
Mostly all prolactinomas shrink in size following treatment with these medications. There is a probability that your vision will improve as the tumour shrinks if your prolactinoma is pressing on the nerves to the eyes. In case of a large prolactinoma, several pituitary scans should be done over the months and years to assess the shrinkage of tumor.
You may be able to taper off the medication with your doctor's guidance if medication shrinks the tumor significantly and your prolactin level remains normal for two years. But never stop taking your medication without your doctor's approval.
Medication during pregnancy:
The most commonly prescribed medicine when treating women who want to restore their fertility is Bromocriptine. However, most patients are recommended to discontinue medication once you become pregnant. But you should seek advice from your endocrinologist before stopping it. In case you have a large prolactinoma or you develop signs and symptoms such as headaches or vision changes, restarting your medication may be recommended to prevent complications from the prolactinoma.
If you are being treated for prolactinoma and you would like to start a family, it is advisable to discuss your options with your doctor before you become pregnant. You will need to continue consulting your endocrinologist throughout your pregnancy, to monitor the progress.

Surgery:

Surgery to remove the tumor will be the only option if drug therapy for prolactinoma doesn't work or you can't tolerate the medication. Surgery may be necessary to relieve pressure on the nerves that control your vision. The type of surgery will depend on the size and extent of your tumor. These include:

Transsphenoidal surgery:

This is the most commonly used surgical procedure, in which the tumor is removed through the nasal cavity. As no other areas of the brain are touched during surgery, complication rates are low and this surgery leaves no visible scars.

Transcranial surgery:

This procedure is used if your tumor is large or has spread to nearby brain tissue which is also known as a craniotomy. The surgeon reaches the tumor through the upper part of the skull. This involves delicately opening the brain to remove the tumor in the pituitary gland. The outcome of surgery depends on the size and location of the tumor, prolactin levels before surgery and the skill of the surgeon.
The higher the prolactin level, the lower the chance of normalizing serum prolactin. Surgery corrects the prolactin level in most people with small pituitary tumors or whose blood prolactin level is below 250 mg/mL. However, many pituitary tumors come back within five years of surgery. For people with larger tumors that can only be partially removed, drug therapy often can return the prolactin level to a normal range after surgery. Drug therapy may also be started before surgery to debulk the tumor for the surgical procedure.

Radiation Therapy:

Surgery is not possible for people who don't respond to medication. In such cases, radiation therapy may be an option.