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Prolactinoma

Prolactinomas are pituitary adenomas that secrete too much of the hormone prolactin (PRL). Prolactin normally is only secreted at a high level in women during ...

condition

Definition

Prolactinomas are pituitary adenomas that secrete too much of the hormone prolactin (PRL). Prolactin normally is only secreted at a high level in women during pregnancy and who are breast-feeding, as prolactin stimulates the breast to produce milk.

Excess prolactin from prolactinomas causes reduced reproductive function by inhibiting secretion of gonadotropin releasing hormone (GnRH) by the hypothalamus. Normally GnRH stimulates the pituitary to produce luteinizing hormone (LH), which stimulates secretion of sex hormones, estrogen by the ovary and testosterone by the testes. Inhibition of GnRH secretion by high levels of prolactin results in reproductive-related symptoms.

Prolactin-secreting pituitary adenomas are the most common type of hormone secreting pituitary adenoma. Most prolactinomas occur in people under age 40, but are rare in children. Women are five times more likely than men to be diagnosed with a prolactinoma. At least half of prolactinomas are microadenomas (small in size, less than 1 cm or 3/8 of an inch in diameter). Microprolactinomas are most commonly found in women. Prolactinomas in men are usually macroadenomas (larger than 1 cm or 3/8 of an inch in diameter).

A multidisciplinary approach is essential due to the involvement of both endocrine and neurosurgical expertise in the appropriate management of patients with prolactinomas.

Symptoms

Because prolactinomas affect reproductive hormones the symptoms are different for women and men.

Women:

  • Irregular periods or cessation of menstrual cycles
  • Galactorrhea, production of milk by the breast (most common in women who are also taking oral contraceptives)
  • Loss of sexual interest
  • Infertility
  • Osteoporosis (due to low sex hormone as a result of the presence of prolactin excess for months to years)

Men:

  • Reduced sex drive or libido
  • Erectile dysfunction
  • Infertility
  • Enlargement of the breasts, called gynecomastia
  • Osteoporosis
  • Visual loss
diagnosis

Diagnosis

A full medical history and physical examination are the first steps to determine the presence of symptoms. Blood tests are taken and measured to indicate pituitary hormone imbalances. The diagnosis of prolactinoma is made by the following:

  • Serum prolactin value: Elevated prolactin of greater than 150 ng/ml generally indicate positive results (levels between 20 and 100ng/ml are also elevated yet can be caused by some medications that interfere with the normal suppression of prolactin secretion from the pituitary gland)
  • Imaging of the pituitary by MRI: Presence of a pituitary tumor on MRI scan. Some small adenomas may be difficult to visualize by imaging, however, elevated prolactin hormone levels will indicate a tumor is present.
treatment

Treatment

Prolactinomas can be treated effectively by medical therapy and rarely require surgical treatment. Medication is required on an indefinite basis and the adenoma usually recurs if treatment is stopped. Regular follow up with measurement of prolactin and assessment of other pituitary function is required, together with MRI scans. If a recurrent tumor is found, additional treatment is necessary.

The primary treatment of prolactinomas is taking medicine to reduce the secretion of prolactin.  Some tumors may require surgical removal.

The goals of treatment are to:

  • Restore production of PRL to normal
  • Stop and reverse the symptoms of prolactinomas
  • Correct other endocrine abnormalities (thyroid, adrenal, ovaries or testes)
  • Remove and/or destroy the tumor to restore endocrine function to normal and to relieve any symptoms directly related to the tumor (headaches, visual disturbance)

Medical Therapy

Dopamine agonist drugs mimic the effect of dopamine, which normally inhibits the secretion of prolactin. These oral medications include:     

  • Cabergoline (Dostinex)
  • Bromocriptine (Parlodel)

Medical treatment with Cabergoline will suppress high prolactin levels to normal in a majority of patients, and in small prolactinomas (microadenomas), normal reproductive function can be restored in 6-8 weeks. Medication is taken on an indefinite basis and is effective in some 90% of prolactinomas.

Medication commonly results in shrinkage of the prolactinoma and after a few years of treatment some small prolactinomas may disappear. In a majority however, continued medical therapy is required. Cabergoline and Bromocriptine are only effective for as long as they are administered and prolactinomas usually enlarge if treatment is discontinued. In women medication usually results in restoration of menstrual cycles and pregnancy may occur. With larger tumors continued treatment is needed throughout the pregnancy but this is not required with smaller tumors.

Surgery

In a a small number of prolactinomas, those which are resistant to Dopamine agonists, surgical treatment is required, either to remove a large tumor or for removal of smaller tumor. This can be achieved by a transsphenoidal operation (through the nose) without disturbing the brain or the eye nerves.

After successful surgery

After complete removal of the tumor, a patient can expect to have the symptoms of a prolactinoma resolve within days. In some cases, pituitary deficiencies may result and can be replaced. In larger tumors, usually in men, reproductive function may not return and additional treatment with replacement testosterone is required.

Radiation Therapy

Radiotherapy is most often performed after surgery has removed the majority of a tumor that does not respond to medication, but some tumor remains which cannot be safely removed. Two main approaches are used are:

  • Focused irradiation (Gamma Knife or Linnac)
  • External pituitary irradiation 
prevention

Prevention

There are no known steps to prevent prolactinomas. Early diagnosis allows for tumors to be diagnosed when they are small, which improves the chance of cure following surgery alone. Early treatment prevents permanent effects, such as osteoporosis, caused by chronic prolactin overexposure.

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