As you probably know at this stage, most Cushing's disease is caused by a pituitary tumor that is over-secreting its hormonal messages to the adrenal glands and causing all the excess stimulation that leads to all the symptoms of Cushing's disease.
Most pituitary tumors responsible for Cushing’s disease are so small that their size is insignificant and we can concentrate on their hormone-producing issues only. In other words, it doesn't matter that the pituitary gland (and its tumor) is located at the base of the brain deep inside the skull as long as the tumor is very small; we can just worry about the hormones it produces and never mind its location.
Unfortunately, approximately 10-20% of dogs with pituitary dependent Cushing’s disease have a tumor that actually is large enough to take up a meaningful 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. Further, a pituitary tumor may not be macro at the time Cushing's disease is first diagnosed but may grow to become macro over the years to come. It is thus a good idea to become familiar with signs to watch for and even better to have periodic brain imaging to check the tumor's changing size.
Illustration by Wendy Brooks, DVM
How Big is too Big?
Ten millimeters (about half of an inch) 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 has adopted the human description. 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 nor do we have rules for smaller dogs with smaller brains. Still, when a dog has a pituitary tumor of 10 mm in diameter and neurologic signs, the tumor should be considered the cause of the signs. In fact, the University of California Davis School of Veterinary Medicine is using 8 mm as their cut-off size for recommending treatment.
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 size and 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 though nothing may be obvious with a formal physical examination. The dog may seem just off, listless or may develop a poor appetite. Occasionally signs are more blatantly abnormal (walking in circles or seizures) but the 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, it should be seen by the veterinarian promptly.
Most dogs diagnosed with pituitary macroadenomas have been diagnosed with Cushing’s disease at least 6 months prior and are probably well controlled on medication, so this condition tends not to appear out of the blue in an otherwise normal dog. In this situation, a macrotumor must be considered, especially if fresh blood testing does not reveal any new diseases. Of course, blatant neurologic signs in a dog with Cushing’s disease would definitely be suspicious for a pituitary macrotumor as well.
Brachycephalic breeds (boxers, pugs etc.) tend to have the biggest pituitary tumors.
How is Diagnosis Confirmed?
Imaging of the brain is required to confirm a pituitary macrotumor and this means either CT (CAT scan) or MRI (magnetic resonance imaging). These procedures are expensive; for example, in Los Angeles brain imaging can easily cost a couple of thousand dollars. Special facilities are needed for the equipment involved, and 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; however, CT is more readily available.
Both these imaging procedures are performed under general anesthesia and involve some risks. The equipment used is large and the patient must spend a good eight to 10 minutes without monitoring inside the equipment. Since MRI uses powerful magnets, normal anesthetic machines cannot be used (because 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, the pituitary area is not nearly as accessible surgically in dogs.
This means that radiation therapy is the only effective treatment available for pituitary macro tumors.
Radiation therapy is performed usually two to three times weekly for four to six weeks and is an expensive undertaking of several thousand dollars. Of dogs that receive radiation therapy, 70 percent will have good improvement as a result with half of them having rapid improvement and the other half improving 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 pigment in the skin and hair 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 if the pituitary tumor responds as well, but one should plan to have to continue treatment for Cushing’s disease despite radiation as at least 50 percent still require treatment for their Cushing's disease.
Very large tumors (greater than 25 mm in diameter) tend to be too big to respond. For this reason, early detection of the tumor is best and allows for more successful 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 might 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 percent 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, 7 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 percent chance of developing clinical signs directly attributable to the macro tumor.
At this time the universities recommend brain imaging on all dogs with pituitary-dependent Cushing's disease if cost is not an issue. UC Davis recommends that any tumor 8 mm in diameter or larger be irradiated and that smaller masses be re-imaged in 12 to 14 months.
Results of the Theon/Feldman 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 five 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, seven 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.