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Dog question about Cushing’s disease : 7 Pituitary Macroadenoma

Most pituitary tumors responsible for Cushing’s disease are microscopic but approximately 10% to 20% of dogs with pituitary dependent Cushing’s disease have a tumor large enough to take up a significant amount of space. These tumors are called macrotumors and, since there is not much extra space within the skull for extra structures, a macrotumor can compress normal brain tissue and lead to neurologic disease.

How Big is too Big?
Ten millimeters (about half an inch) in diameter is the size a pituitary tumor must reach to be categorized as a macrotumor in a human being. Dogs obviously have more variance in the size and shape of their skulls than do people, thus it may be inaccurate to use the human definition for dogs but so far the veterinary profession is using this size definition. It appears that up to 50% of dogs with pituitary tumors of this size do not have concurrent neurologic disease. We do not have information regarding how many of these asymptomatic dogs will go on to develop neurologic disease. Still, when a dog has a tumor of this size and neurologic signs, the tumor should be considered the cause of the signs.

Is this Cancer?

Not in the way most people think of cancer. Pituitary macrotumors are almost always benign in that they do not spread in any way. They can, however, produce harm simply because of their location.

When Would an Owner Suspect a Pituitary Macrotumor?
When a pituitary mass begins to expand, the owner is likely to notice subtle changes in behavior although nothing may be obvious with a formal physical examination. The dog may seem just “off,” listless or off food. Occasionally signs are more blatantly abnormal (walking in circles or seizures) but a more subtle start is more common. It should be noted in particular that it is extremely abnormal for a dog with Cushing's disease not to have a good appetite even while on therapy. If a dog with Cushing's disease develops a poor appetite, see the veterinarian promptly.
Most dogs diagnosed with pituitary macroadenomas have been diagnosed with Cushing’s disease at least 6 months prior so this condition tends not to appear out of the blue in an otherwise normal dog (though in some dogs, the symptoms of Cushing’s disease come after the pituitary macrotumor has been found). Neurologic signs in a dog with Cushing’s disease would definitely be suspicious for a pituitary macrotumor.

Brachycephalic breeds (boxers, pugs etc.) tend to have the biggest pituitary tumors.

How is Diagnosis Confirmed?
Special imaging of the brain is required to confirm the presence of a pituitary macrotumor and this means either CT (cat scan) or MRI (magnetic resonance imaging). These procedures are expensive (in the Los Angeles area CT runs around $700 and MRI runs around $1000). Special facilities are needed for the equipment involved, thus referral to a specialty hospital is usually required. MRI is felt to be superior for imaging the pituitary gland and is the preferred imaging method for this situation.

Both these imaging procedures are performed under general anesthesia and involve some special risks. The equipment used is large and the patient must spend a good 8 to 10 minutes without monitoring inside the equipment. Since MRI uses powerful magnets, normal anesthetic machines cannot be used (as they are metal) and injectable anesthetics are often needed. Injectable anesthesia is not as easily controlled as inhalation.

At this time there is no blood test that can distinguish a macrotumor from a microtumor but some promising tests are currently under investigation.

How is a Pituitary Macrotumor Treated?
While surgical removal of pituitary tumors is feasible in humans, this area is not nearly as accessible in dogs. This means that radiation therapy is the only effective treatment available for pituitary macrotumors.

Radiation therapy is performed usually 2 to 3 times weekly for 4 to 6 weeks and is an expensive undertaking in the Los Angeles area (usually $3000-$5000). Of dogs that receive radiation therapy 70% will have good improvement as a result; half of those will have rapid improvement and the other half will improve in the month or two following the course of therapy.

Radiation therapy is not without complication. Common problems associated with this treatment include loss of skin and hair pigment in the area irradiated, hearing loss, and sometimes problems with tear production in the eyes.

Many dogs experience a resolution of their Cushing’s disease as the pituitary tumor responds as well, but plan to have to continue treatment for Cushing’s disease despite radiation.

Early detection of the tumor allows for early treatment and better response to radiation therapy.

Is Radiation Therapy likely to be Curative?
Unfortunately, no. The pituitary tumor is likely to recur in time (ranges are reported at 2.5 to 26 months for recurrence). Keep in mind that these patients are geriatric and may not live long enough to see their tumor recur. For more details, see the results of the Theon/Feldman study below.

Should all Dogs with Pituitary Cushing’s Disease be Imaged to Potentially Catch the Tumor Early?
This is a difficult question to answer; there are arguments either way. Imaging is not without risk since it involves general anesthesia and Cushing's disease patients are generally elderly. Further, imaging is expensive and there is only a 10 to 20% chance of finding a tumor big enough to warrant therapy. By the time it has been determined that a dog has Cushing's disease, many owners are tired of the seemingly endless progression of testing and associated expense.

On the other hand, imaging early will identify dogs at risk for the development of a macrotumor. For example, a dog with a small tumor (less than 4 mm in diameter) at the time of Cushing's diagnosis is unlikely to live long enough for that tumor to quadruple in size to a tumor large enough to warrant attention. A dog with a larger tumor (say, 8 mm in diameter) could easily have a tumor of significant size in a year or two and such a patient should be re-imaged in 12 to 16 months to re-evaluate the tumor size. A tumor 10 mm in diameter at the time of the diagnosis of Cushing's disease is probably large enough to warrant radiotherapy right off the bat even if no signs are yet seen. If this last patient is not imaged at the beginning, it is likely that the tumor will not be treatable when it is big enough to create more obvious symptoms.

A dog with an initial tumor size greater than 10 mm in diameter has a 66% chance of developing clinical signs directly attributable to the macrotumor.

Results of a Recent Study
(Theon, A.P. and Feldman E.C. Megavoltage irradiation of pituitary macrotumors in dogs with neurologic signs. Journal of the American Veterinary Medical Association, Vol 213, No 2, July 15, 1998.)

Overall survival was increased in macrotumor patients with radiotherapy. The average survival time was approximately 5 months from the time neurologic problems had started (patients without neurologic problems were not included in this study). Out of 24 dogs in the study, 7 survived longer than one year from the time of tumor diagnosis. If neurologic problems were categorized as “severe” (i.e., there was a compromised ability to walk), survival time was not improved by radiotherapy. Milder neurologic deficits were associated with longer survival.

In this study, both dogs with ACTH secreting tumors (the kind that cause Cushing’s disease) and pituitary tumors that were hormonally inactive (the kind that do not cause Cushing’s disease) were studied. The dogs with ACTH secreting tumors had better responses to radiotherapy than those with inactive tumors; however, in these patients, radiotherapy yielded a better chance of resolving neurologic problems than it did in resolving the symptoms of Cushing’s disease.
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