Adrenal Glands

Adrenal gland enlargement and Mitotane (Lysodren Rx) treatment

Question: Dr. Richards,

Thank you for the quick response to my last question. We just received news that our 13 year old golden retriever does not have Cushing's disease. He was tested (dexamethasone and other tests) and all was negative. He has been drinking and urinating excessively. Now after an ultrasound it seems the adrenal gland is slightly enlarged. He has no tumors and our vet (who we think is terrific) wants to start a program of lysodren which we were informed kills the cells of the adrenal cortex selectively. I wanted to know your thoughts on this drug and problem. Thanks again, Gina

Answer: Gina-

There are several possibilities when adrenal gland enlargement is identified. The most likely problem is hypertrophy of the adrenal gland due to stimulation from the pituitary gland, which is one of the two major causes of hyperadrenocorticism (HAC, Cushing's disease). In this case, there is not an adrenal gland tumor. The adrenal gland is doing exactly what it should do in response to stimulation from the pituitary gland.

If an adrenal gland tumor is present, it may be one of several types. (metastasis from another site, adrenal gland adenoma, adrenal gland adenocarcinoma, pheochromocytoma). In this case, the problem is identifying the type of tumor present.

Ultrasonagraphy of the adrenal glands seems to be difficult, based on conflicts among the reported findings in adrenal gland tumors among the clinical studies that I can find. I do not do ultrasonagrahic examinations in my practice and my personal experience with this technique is minimal, so this is simply my impression based on reviewing the available literature. Given the conflicts in the literature, though, I think that I would be cautious about using mitotane (Lysodren Rx) for an adrenal gland tumor unless there was support for the diagnosis of hyperadrenocorticism (Cushing's disease) in the lab work, since this therapy is directed at adrenal gland carcinomas and adenocarcinomas and won't work for the other types of tumors. The classic case of an adrenal gland adenoma or carcinoma would be one large adrenal gland and one atrophied (smaller than normal) adrenal gland, but in several studies this didn't always hold true. The opposite adrenal gland can be enlarged because there is concurrent pituitary dependent Cushing's disease, because of a tumor affecting that gland too (adrenal origin or other origin) and also simply because it didn't atrophy as expected.

There are approximately 20 possible causes of increased drinking and increased urination in dogs. Many of these can be ruled out quickly based on the dog's sex, the medical history and general chemistry profiles. The remaining possibilities are then usually the hormonal diseases (hyperadrenocorticism, hypoadrenocortisicm, diabetes insipidus), infections (pyelonephritis both sexes, pyometra in females) and cancers (pheochromocytomas and metastatic cancers producing pseudohormones). Sorting through these conditions can be very difficult.

If both a low dose dexamethasone suppression test and ACTH response test fail to show the presence of hyperadrenocorticism, the likelihood that this is the problem is low, but unfortunately, not totally ruled out. There are dogs who have Cushing's disease who do not test positive for it on either of these tests. When this happens, an effort should be made to eliminate the other possible causes of increased drinking and increased urinating. If no other cause can be found and if there are other signs of Cushing's disease, such as thinning of the hair coat, thinning of the skin, a pendulous abdomen, panting, muscular weakness, calcinosis cutis (calcium deposits in the skin), recurrent bladder infections or other less common clinical signs, then it is reasonable to treat for Cushing's disease to see if a response to therapy can be obtained. This has to be done very carefully, since mitotane does kill adrenal gland tissue, which can cause significant problems if hyperadrenocorticism is not present.

With all of that in mind, there is still the question of what to do. It is important to be sure that an effort has been made to rule out as many of the other causes of increased drinking and urinating as possible. If this has been done to your vet's satisfaction (and yours) and if he or she still believes that Cushing's disease is most likely even without the positive test results it is considered to be reasonable by many internal medicine specialists to attempt treatment to see if it will help. On the other hand, if the only symptom is increased drinking and urinating and if that doesn't bother you or your dog too much, it is also reasonable to do nothing and wait to retest at a later date. Sometimes, over time, further symptoms develop or lab results finally match a disease process.

Mitotane (Lysodren Rx) does selectively destroy adrenal gland tissue. As long as that is appropriate for the disease process, it is a good medication. Some dogs do react adversely to it and we have had one death using it that we really feel was a direct result of the medication and not from creating hypoadrenocorticism accidentally. We have also had several dogs that we have treated with mitotane who did ultimately develop hypoadrenocorticism that required therapy. Some of these eventually returned to a Cushingoid state but we did treat one dog life long for Addison's disease that we created with the medication. In a few dogs who have Cushing's disease, mitotane brings a sudden worsening of clinical signs when it is used but this is a complication of the disease more than of the medication since it is likely this would have happened quickly, anyway. If you and your vet do elect a therapeutic trial of the medication you should watch carefully for signs of problems, such as a loss of appetite or weakness and it would be best to monitor water intake as closely as possible so that you can alert your vet when water intake starts to decrease so that dosage adjustments can be made accordingly. I am sure that your vet will go over this type of thing with you again but do remember that you play a big role in the success or failure of Lysodren therapy.

I think that there are several notes with the list of possible differentials for increased drinking and urinating on our site but if you can't find them, let me know and I'll send you a new one as I am working on this for next month's VetInfo Digest.

Mike Richards, DVM