Patient information: Gonadotroph adenomas and other nonfunctioning adenomas

PITUITARY TUMORS OVERVIEW

Pituitary tumors are abnormal growths in a small organ in the center of the brain called the pituitary gland (figure 1). This gland releases growth hormone, prolactin, and hormones that control the thyroid gland, adrenal glands and reproductive organs.

Most pituitary tumors are adenomas. Pituitary adenomas that produce hormones are said to be "functioning"; those that do not produce hormones are called "nonfunctioning". The most common nonfunctioning pituitary adenomas are called gonadotroph adenomas.

Nonfunctioning adenomas do not overproduce hormones, thus most people do not have noticeable signs or symptoms in the early stages. Instead, these adenomas often grow until they become so large that vital structures near the pituitary gland are affected. One such structure is the nerve to the eyes, which can become compressed as the adenoma grows, causing vision loss.

PITUITARY TUMOR SYMPTOMS

Vision loss — Loss of vision, double vision and headache are the most common symptoms of non-functioning pituitary adenomas. Loss of vision may affect one or both eyes. Vision becomes impaired when the growing adenoma compresses the nerves to the eyes.

Vision is usually lost so slowly that many people do not seek help for months or even years. Even at this time, the adenoma may not be detected.

Other symptoms — Other symptoms caused by growth of the adenoma include the following:

• Headaches
• Double vision
• Leakage of cerebrospinal fluid from the nose
• Sudden bleeding into the adenoma, causing excruciating headache and double vision

Hormonal symptoms — Some people with gonadotroph adenomas have symptoms due to excessive secretion of hormones, FSH and LH.

High levels of gonadotropins

• Premenopausal women with excessive secretion of follicle-stimulating hormone (FSH) may have irregular menstrual periods and multiple cysts in the ovaries.
• Prepubertal girls with excessive FSH secretion may have breast development and vaginal bleeding.
• Men with excessive luteinizing hormone (LH) production may have high testosterone levels.
• Prepubertal boys with excessive LH production may have premature puberty.

Low levels of gonadotropins — Symptoms may also occur as a result of low levels of pituitary hormones; this can occur when normal pituitary cells are compressed by the tumor. When these cells are compressed, lower levels of hormones from the thyroid, adrenal glands, and testicles or ovaries may result. Common symptoms of low levels of these hormones include fatigue, nausea, vomiting, weakness, loss of sexual drive, and lack of menstrual periods.

PITUITARY TUMOR DIAGNOSIS

Gonadotroph and other non-functioning pituitary tumors are usually diagnosed when they become large enough to cause neurologic symptoms such as vision loss. They may also be noticed when an imaging test (eg, MRI or CT scan) of the head is performed for an unrelated reason (eg, after a car accident). MRI is preferred because it provides the clearest images of the pituitary and associated structures.

If a mass is seen with MRI, blood testing is done to determine if the mass is made of pituitary or non-pituitary origin. In some people with gonadotroph adenomas, there are higher than normal blood levels of FSH or LH. As a result, some women have high levels of estrogen (estradiol) and some men have high levels of testosterone. However, some gonadotroph adenomas do not overproduce these hormones. In this case, other hormone levels are measured to determine the if mass is another type of adenoma (eg, lactotroph adenoma, somatotroph adenoma) (table 1).

PITUITARY TUMORS TREATMENTS

Surgery — Surgery is currently the only treatment that provides rapid relief of neurologic symptoms for people with non-functioning pituitary adenomas. Surgery reduces the size of the tumor and decreases production of hormones in more than 90 percent of people; it improves vision in about 70 percent of people [1].

Surgery is performed through the sinus behind the nose (called the sphenoid sinus), and is called transsphenoidal surgery (figure 2). A small incision is made inside the nose, then extended through the sphenoid sinus. This allows the surgeon to visualize and remove the adenoma. An endoscope (a thin, lighted tube with a camera) may be used to ensure that the adenoma has been removed completely.

Complications — The risk of surgical complications is lower when the procedure is performed by a surgeon who has significant experience (eg, more than 500 transsphenoidal procedures) operating on the pituitary gland.

Diabetes insipidus (DI) is a disorder that commonly occurs in the days following transsphenoidal surgery. DI causes insufficient secretion of a hormone (vasopressin, also called antidiuretic hormone), which causes intense thirst and overproduction of urine (polyuria). In other people, there is excessive production of vasopressin, causing decreased urine production; this is known as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). These abnormalities usually do not last more than four to five days after surgery, but permanent diabetes insipidus can occur.

Serious complications of surgery in the immediate postoperative period occur in less than 5 percent of patients. They include worsening vision, excessive bleeding, and leakage of cerebrospinal fluid (CSF) from the nose, which can lead to meningitis.

Postoperative outlook — Surgery may be followed by a decrease, increase, or no change in hormone secretion by normal pituitary cells. Blood tests are performed four to six weeks after surgery to determine the function of these cells. Any hormonal deficiencies are treated, based upon these results.

Other blood tests may be recommended if there was excessive hormone production prior to surgery; these results can indicate if there is any remaining adenoma tissue. If there was vision loss before surgery, this should also be evaluated at the postoperative visit.

Following the postoperative visit, most experts recommend that patients visit their doctor every six to 12 months for an MRI and blood testing. Vision should also be periodically evaluated if it was affected by the tumor. If the MRI shows no tumor regrowth after a year or two, the interval between scans can be increased.

Radiation — Radiation therapy may be administered 6 to 12 months after surgery if the MRI shows that a large amount of adenoma tissue remains. Radiation therapy can help to prevent this tissue from regrowing.

Those who have little remaining adenoma tissue after surgery can be monitored by MRI, and radiation can be administered if substantial regrowth is detected. In a group of 65 patients considered at low risk for recurrence after surgery, 21 (32 percent) had evidence of tumor regrowth during a period of 76 months [2].

Types of radiation — Many types of radiation are available. The type that is recommended is often based upon the type that is available at the nearest medical center. All types use computer guidance of the radiation to the adenoma tissue. The types available vary by:

• The source of the radiation (linear accelerator, cobalt source, or proton beam)
• The number of doses, either multiple doses (fractionated) or a single dose. Single dose forms are misleadingly called "radiosurgery" (eg, gamma knife), which does not involve surgery but instead uses radiation from a gamma source. Single dose forms deliver much more radiation at once compared to fractionated forms. Therefore, single dose forms cannot be used when the adenoma tissue is too close to the optic chiasm, which is sensitive to damage from high doses of radiation.

Efficacy — Radiation is usually successful in stopping or shrinking growth of a pituitary adenoma. Most evidence about the effects of radiation on size come from older studies using fractionated radiation. No evidence so far suggests that newer forms of radiation are more or less effective in controlling adenoma size.

Side effects — Side effects of radiation can occur both during therapy and for at least 10 years after therapy.

• During radiation, nausea and lethargy may occur.
• After radiation treatment, the most serious potential side effect is nerve damage, especially the nerves to the eyes, but also to nearby parts of the brain. The chance of this side effect is very low, but still possible, even with new computer methods that target the radiation.
• The most common complication after radiation treatment is some loss of function in the remaining pituitary, which was not part of the adenoma. There is an approximately 50 percent likelihood that at least one pituitary hormone that was normal prior to radiation will become below normal within the ten years after treatment.

Drug therapy — Currently, there is no medication that consistently and substantially reduces the size of non-functioning pituitary tumors. Several medications, including dopamine-like drugs and octreotide, have been reported to improve vision in a few patients with clinically non-functioning pituitary adenomas. However, these medications did not reduce the size of the adenoma.

No treatment — Gonadotroph and other non-functioning pituitary adenomas that do not cause symptoms and are not an immediate threat to vision may not require treatment, especially if the patient is elderly or ill. This situation is increasingly common because an increasing number of adenomas are detected when MRI is performed for other reasons, such as head trauma. Hormonal deficiencies should still be treated, and reevaluation of adenoma size and function of the normal pituitary should be performed at yearly intervals.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:

Professional Level Information:
Causes, presentation, and evaluation of sellar masses
Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning adenomas
Overview of precocious puberty
Pituitary incidentaloma
Treatment of gonadotroph and other clinically nonfunctioning adenomas

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• The Endocrine Society

      (www.endo-society.org)

• The Hormone Foundation

       (www.hormone.org/public/pituitary.cfm, available in English and Spanish)

• Pituitary Tumor Network Association

      Telephone: 805-499-9973
      (www.pituitary.org/)

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