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Pituitary Adenomas

Definition

Pituitary adenomas are benign tumors found within the pituitary gland. The pituitary gland is located at the base of the brain towards the front of the head. The pituitary gland is often referred to as the “master hormone production center” since it controls many of the hormones produced in the body, including hormones that regulate growth and the activity of other glands. A pituitary adenoma is an abnormal growth, or tumor, in this gland. When a tumor arises in this area, hormones are often affected. 

Pituitary adenomas are generally categorized by their size and by the hormones involved. Since the pituitary gland is small in size (about the size of a pea), pituitary adenomas tend to be relatively small. Microadenomas are very small (less than 1 cm or 3/8 of an inch in diameter). Macroadenomas are greater than 1 cm and generally range in size between 1.1 cm and 6 cm and can extend beyond the pituitary gland. 

Two common misconceptions exist about pituitary adenomas. One false idea is that a pituitary tumor is a “brain tumor.”  The pituitary gland is not inside the brain and pituitary tissue is different from brain tissue. Since the pituitary gland is located at the base of the brain and is connected to the brain by a thin stalk, there is often confusion, particularly by insurance companies, about the classification of a pituitary tumor. A pituitary tumor is NOT a brain tumor.

Another common misconception is that pituitary adenomas are cancerous. In over 99% of patients, it is not a cancer. It is benign and will not spread to other parts of the body. Although the tumor is benign, it can cause problems because of its size, including loss of vision, loss of normal pituitary function (hypopituitarism) and headaches, or because of excessive hormone production by the tumor.

Causes

Pituitary adenomas are common. In autopsy studies of patients who did not have known pituitary disease, as many as 26% had a small tumor (adenoma) in the gland.

Studies have shown that a change in the DNA (genetic mutation) of a pituitary cell can cause unregulated growth of that cell, resulting in a pituitary tumor, called an adenoma. There are no known environmental causes.

A very uncommon type of pituitary tumor is inherited, called multiple endocrine neoplasia, type I (a condition that increases the risk of developing pituitary, pancreatic and parathyroid tumors). In this situation, there is usually a family history of endocrine tumors, most commonly a parathyroid tumor causing high blood calcium levels, a pituitary tumor which may or may not produce an excessive amount of a hormone and less commonly, a neuroendocrine tumor of the pancreas. This occurs in fewer than 4% of patients with a pituitary tumor.

Symptoms

The symptoms of a pituitary adenoma depend on the type of tumor and the size of the tumor. A large tumor may cause loss of vision, particularly peripheral vision, if it compresses the optic chiasm [where the optic (eye) nerves come together, located above the pituitary gland]. Headache may also occur (the type of headache varies from patient to patient). Headache may occur with a large or a small tumor.

A tumor may interfere with normal pituitary function, causing hypothyroidism (low thyroid hormone level), adrenal insufficiency (low cortisol level) or hypogonadism (loss of sexual function and fertility in men, loss of menstrual periods or fertility problems in women).

Occasionally a pituitary tumor causes diabetes insipidus, which results in frequent urination and excessive thirst. Diabetes insipidus is not high blood sugar levels; it is a problem with the ability of the kidney to retain fluid because of a deficiency of the pituitary hormone vasopressin (also called antidiuretic hormone) that regulates water balance.

Specific types of tumors cause various symptoms and changes in body function:

  • Prolactinoma
  • Acromegaly
  • Cushing's
  • TSH secreting tumor
  • Non-secretory tumor: This is a tumor that does not produce an excessive amount of a pituitary hormone that can be measured in the blood. This type of tumor most commonly causes sexual dysfunction in men and loss of regular menses and infertility in premenopausal women. This type of tumor is usually detected after it has become a large, causing loss of vision and/or headache and/or hypogonadism (loss of sexual function in men, loss of menses in premenopausal women), hypothyroidism (low thyroid hormone level) or adrenal insufficiency (low cortisol level).
  • Craniopharyngioma/Rathke's cleft cyst

The pituitary gland may also develop a pituitary cyst. Cysts occur commonly in the ovaries and thyroid gland. A cyst in the pituitary gland is benign (not cancer), but causes a problem because of enlargement, causing headache and/or interference with normal pituitary function. Most common symptoms are headache and, if the cyst is large, loss of vision and loss of normal pituitary function. Sometimes a cyst may cause frequent urination and excessive thirst (diabetes insipidus).

Diagnosis

A thorough history and physical examination is necessary and should evaluate potential endocrine, visual and neurological deficits. An endocrinologist, neurosurgeon and neuro-ophthalmologist are often involved in the evaluation.

Diagnostic evaluation may include:
  • Medical history to assess endocrine symptoms (menstrual history, questions about frequent urination).
  • Blood tests to measure hormone levels, including assessment of adrenal cortisol production, thyroid function, growth hormone production, gonadal function (Men: testosterone and LH levels; Premenopausal women: LH and estrogen levels), prolactin level and alpha subunit level and blood sugar levels, as well as to identify other underlying conditions that may be causing symptoms.
  • Urine tests to measure excretion levels of certain pituitary gland hormones (beta human gonadotropin, cortisol 24 hour urine test).
  • Visual field tests to perform a thorough eye exam, including checking for problems with visual acuity, double vision and peripheral vision.
  • MRI scan to allow the identification of the pituitary tumor and determine whether it is pressing on vital structures, such as the optic chiasm.
Special Tests
  • Glucose tolerance test, the standard test for acromegaly.
  • Petrosal sinus sampling, dexamethasone suppression test and corticotropin-releasing hormone (CRH) test. These are the best tests to see if excessive secretion of hormones from the adrenal gland is due to a pituitary adenoma.

The diagnosis of a pituitary tumor is a process that requires multiple tests. While elevation of a pituitary hormone may indicate the specific type of pituitary tumor, some tumors may not produce hormone elevations at all. Some patients may have more than one pituitary disorder. For example one tumor may secrete both GH and prolactin.

Tumors may also interfere with the secretion of other pituitary hormones and cause a deficiency of other pituitary hormones. A positive MRI scan usually indicates the presence of a tumor, but some tumors are so small they may not be visualized on the MRI scan.

Due to the complexity of diagnosis, a multidisciplinary approach using endocrinologists, neurosurgeons, radiologists, neuro-ophthamolgists and pathologists is essential for proper assessment of pituitary disorders.

Treatment

The best treatment depends on the type of pituitary tumor.

Prolactin-producing tumors are most successfully treated with medical therapy (pills). The best treatment for other types of pituitary adenomas is removal of the tumor by an experienced neurosurgeon who performs pituitary surgery frequently. Although most neurosurgeons have some experience with pituitary surgery, only a few have devoted their career to pituitary surgery and have the best records of success.

The goals of treatment are to:

  • Restore production of hormones to normal
    • Stop and reverse the symptoms of hormone overproduction or deficiency
  • Correct other endocrine abnormalities (adrenal, thyroid, growth hormone production, 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, such as visual loss and headaches

Medical Therapy

Any medical therapy for a pituitary tumor should reduce hormone overproduction by the tumor, and, ideally, decrease the size of the pituitary tumor so that if there is a visual abnormality, it is improved.

Reduction in tumor size should also improve or relieve headache associated with the tumor.

Since not all pituitary adenomas produce an excessive amount of a hormone or hormones, the only measure of successful medical therapy for a non hormone-producing tumor is the effect on tumor size and symptoms (visual problems, headache).

Surgical Treatment

Some patients are not cured with surgery. The reason for this is most commonly because of the size of the tumor: the larger the tumor, the less likely it can be removed completely. Additionally, the tumor may have spread to nearby structures such as bone, the cavernous sinus (location of carotid artery and the nerves controlling eye movements) and the membrane surrounding the gland (dura mater). In this situation, the neurosurgeon removes all that can be safely removed, but if the tumor has invaded surrounding structures such as bone or the cavernous sinus or the membrane covering the pituitary, excessive hormone production may persist and the tumor may regrow.

Surgery is usually the first step to remove as much of the tumor as possible, since the medical treatments do not always shrink the tumor and, if present, relieve the pressure on the optic nerve or improve vision problems. 

Another minority of patients with pituitary tumor will have a recurrence of the tumor. Even though the tumor was successfully removed by surgery originally, years later the tumor may come back. Additional treatment is required in either the form of medical therapy, repeat surgery or radiation therapy.

Radiation Therapy

Radiation is used when there is tumor remaining after surgery, to prevent regrowth or when surgery is cannot be performed. Since these tumors are slow growing, radiation treatment is not routinely recommended. Radiation does not produce an immediate effect to lower excessive hormone production or shrink the tumor. For example, in patients with acromegaly (excessive growth hormone production), growth hormone levels may remain elevated for 10 to 20 years after conventional radiation.

Two general types of radiation are used:

  • Conventional (fractionated) radiation refers to delivery of a small amount of radiation every day for 4 to 5 weeks.
  • Stereotactic radiation refers to delivery of a precisely focused beam of radiation to the remaining tumor, usually as one or a few more treatments (Gamma Knife, LINEAC, Cyber knife, proton beam). Find out more about Gamma Knife treatment at UVA.

The decision about which type of radiation to use is made only after a careful review of the MRI scan to assess the size and location of the residual tumor. A large tumor that is near the optic chiasm (eye nerves) is not suitable for stereotactic radiation because of the intensity (radiation dose) of the single treatment and risk of damage to vision. Stereotactic radiation is only appropriate for a small tumor that is not near the optic chiasm. 
Side effects of radiation include:

  • Loss of normal pituitary function
  • Damage to vision (uncommon)

These risks must be weighed against the risk of tumor regrowth. Hair loss does not usually occur. 
Hormonal deficiencies may occur within a year or many years after treatment. One study reported that 50% of patients treated with conventional radiation developed deficiency of one or more pituitary hormones within two years of treatment. Studies of Gamma Knife focused radiation suggest that about one-third of patients develop a pituitary hormone deficiency two to three years after treatment. It is expected that this percentage will increase with longer time after the treatment. Although development of a pituitary hormone deficiency is not desirable, hormone replacement therapy is available.

Hormonal Deficiency

If the pituitary gland does not recover normal function after surgery or radiation, hormone replacement is usually life long. Depending on the tumor type, the treatment and the effects of treatment, some patients have return of normal pituitary function and replacement hormone(s) can be stopped. This should only be done with the appropriate blood testing to make sure the pituitary gland has resumed normal function. Do not stop the medication on your own without supervision from your endocrinologist. 

If a patient requires steroid (cortisol) replacement, a "Medic Alert" bracelet or necklace should be worn at all times. Another illness such as flu, pneumonia or an accident requires an increase in the steroid dose. With attention to these important details, a patient with a pituitary tumor should have a full and productive life.

Prevention

There are no known steps to prevent pituitary adenomas. 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 caused by chronic hormonal overexposure. 

If untreated, pituitary adenomas can lead to:

  • Blindness
  • Severe headaches
  • Complications related to specific high hormone levels:
    • Acromegaly: heart disease, high blood pressure, abnormal lipids (cholesterol), diabetes, sleep apnea, joint disease (osteoarthritis), colon polyps
    • Cushing's disease: heart disease, abnormal lipids (cholesterol), diabetes mellitus, high blood pressure, osteoporosis and bone fractures, depression, memory loss
    • Prolactinoma: osteoporosis, increases the risk for bone fractures, loss of muscle mass, anemia, loss of regular menstrual cycles, infertility
    • Non-functioning adenoma, craniopharyngioma, Rathke's cleft cyst, pituitary cyst
  • An increased risk of dying earlier than expected (mainly in patients with uncontrolled acromegaly or Cushing's disease

Lowering of the hormone level to normal and removing the tumor reduces these risks. With prompt and proper treatment and, if necessary, appropriate hormone replacement, patients who have had a pituitary tumor can expect to live a normal, productive life. 

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Advanced Treatment

Treatment of tumors at the base of the skull is highly complex. These tumors are hard to reach, and surgery is a delicate process that can affect many areas of the body.

At UVA’s Skull Base Center, we have a team of experts who provide comprehensive management of these challenging tumors.

Treatment approaches include Gamma Knife Radiosurgery, for faster planning and treatment of complex tumors without invasive surgery.