We will begin with the assumption that the presence of an adrenal tumor has already been confirmed with either blood testing, special imaging or both. There are two questions that must be answered next:
- IS THE TUMOR BENIGN OR MALIGNANT?
- SHOULD YOU CHOOSE SURGICAL TREATMENT OR MEDICAL MANAGEMENT?
BENIGN VS. MALIGNANT While only approximately 15% of canine Cushing’s syndrome patients have adrenal tumors, half of these patients will have benign tumor and half will have malignant tumors. The choice of therapy may well depend on which is present, If imaging has not yet been performed, this is the time to do so. Chest radiographs will be important as malignant adrenal tumors tend to spread to the chest. If such spread is seen, the tumor can be assumed to be malignant. Absence of such findings does not mean the tumor is benign. Ultrasound of the abdomen (or even CT scanning or MRI imaging) will be needed to determine the size of the tumor, and to check for invasion of local abdominal tissues (esp. liver). Between evaluation of the chest and the abdomen, it may be possible to non-invasively determine if the tumor is malignant. It should be noted that the absence of tumor spread does not mean that the tumor is benign. WHAT IF IMAGING INDICATES THAT THE TUMOR IS BENIGN? If the adrenal tumor is benign, there is an excellent chance for complete recovery if the tumor is surgically removed. The smaller the tumor, the easier the surgery, though the surgery involves delicate tissue in a difficult area. WHAT IF IMAGING INDICATES THAT THE TUMOR IS MALIGNANT? If there is obvious tumor spread, surgery may be too risky. The decision to proceed with medical therapy will depend on patient debilitation and the degree of tumor spread versus the severity of the clinical signs of Cushing’s disease. Palliation of the clinical signs may be achieved with just partial removal of the tumor. Medical management with high doses of lysodren would be a fair alternative. WHAT YOU SHOULD KNOW ABOUT SURGERY
- Removal of the adrenal gland is a relatively difficult surgery and is probably best left to board certified surgeons. (The adrenal gland is located between the aorta, which is the largest artery of the body, the renal artery and vein, which are the sole blood supply to the kidney, and the phrenicoabdominal artery. This especially vascular area is half-jokingly referred to by surgeons as the Bermuda triangle. Surgery here is not for the inexperienced.)
- Risk of bleeding is higher for larger tumors especially if they are malignant and have invaded local structures. It is quite possible that the full extent of such invasion will not be apparent prior to the time of surgery.
- Animals with Cushings syndrome have poor healing ability and tend to have high blood pressure. Several months of medical therapy (i.e. lysodren, anipryl, or ketoconazole) prior to surgery may be a good means to strengthen the patient, especially if the tumor is believed to be benign. If the tumor is believed to be malignant, there may not be time for such stabilization.
- The dog’s natural cortisone mechanisms will have been suppressed by the tumors presence. Several months of prednisone will likely be required at home. Some patients require florinef as an additional supplement ACTH stimulation test are used to monitor the need for medication.
- Adrenal tissue is notoriously difficult for pathologists to grade as benign or malignant. It is possible that as tumor initially graded as benign wil turn out later to be malignant.
- A statistical survey of 63 dogs under-going sugery for their adrenal tumors:
- 6% (4) had inoperable tumors and were euthanized on the surgery table.
- 29% (18) died either in surgery or shortly thereafter due to complications.
- Average life span for dogs undergoing surgery is 36 months (this includes averaging in those who died shortly after surgery)
MEDICAL THERAPY FOR THE ADRENAL TUMOR Lysodren is a drug of chemotherapy which is able to erode the cortisol-producing layers of the adrenal gland. This ability hs made lysodren, the traditional medication for the treatment of pituitary Cushing’s disease and it turns out the adrenal tumors will respond to higher doses as well. The higher doses needed to control adrenal tumors tend to produce more lysodren reactions than are seen in the treatment of pituitary tumors. The average survival time for this type of therapy is 16 months. For a review of the basics of lysodren therapy click here. ADVANTAGES OF KETOCONAZOLE OVER LYSODREN Because of the nature of the adrenal interference produced by Ketoconazole, it is not possible to induce Addison’s disease. Because Addison’s disease is not of concern, monitoring tests are not necessary when Ketoconazole is used to treat Cushing’s disease. Ketoconazole lists vomiting and diarrhea as potential side effects as does Lysodren but with ketoconazole, no “antidote” pills are needed. Ketoconazole is simply discontinued until the side effects resolve. The dose is modified and re-started. ADVANTAGES OF LYSODREN OVER KETOCONAZOLE Ketoconazole is given twice a day indefinitely whereas Lysodren is given once or twice a week, a much more convenient scheduling. Ketoconazole is enormously expensive even when compared to the cost of all the monitoring tests associated with Lysodren. Because few people can afford to treat with Ketoconazole, most veterinarians do not have a lot of experience using this drug. Most veterinarians have extensive experience with Lysodren. Approximately one dog in five will not respond to Ketoconazole. This is thought to be a problem with absorption of the drug from the intestinal tract. L-DEPRENYL (BRAND NAME: ANIPRYL): THE LATEST INNOVATION So the search for a better Lysodren alternative continued. L-deprenyl represents a completely different approach. Rather than trying to interfere with the adrenal gland’s over-production of steroid hormones, L-deprenyl addresses the pituitary tumor directly. Studies with L-deprenyl began when it was found that this medication might be helpful in treating humans with Parkinson’s disease. Research in dogs, however, uncovered some surprising results involving ACTH release from the pituitary gland. Previously in this web site, we reviewed the feed back loop involving the regulation of adrenal secretion by the pituitary gland. In fact, only part of the pituitary gland (the anterior pituitary) is involved in the feedback loop presented. There are two other parts to the pituitary gland: the intermediate part and the posterior part. The posterior part is involved in the regulation of unrelated hormones and does not concern us but the intermediate part is definitely able to secrete ACTH and is not subject to the same feedback loop as the anterior pituitary is. So how might we influence ACTH secretion of the intermediate pituitary gland? Research using L-Deprenyl showed us that ACTH secretion in this area of the pituitary is governed by the neurotransmitter: dopamine. When dopamine levels are high, ACTH secretion shuts down. Pituitary tumors are not very responsive to normal regulatory mechanisms in the body, but most pituitary tumors in dogs with Cushing’s disease are not located in the intermediate pituitary area. This means the intermediate area is still able to respond normally to dopamine regulation. So how do we raise dopamine levels in the pituitary gland? L-Deprenyl inhibits the enzymes involved in degradation of dopamine. This means that the dopamine present lasts much longer. It also stimulates the production of other neurotransmitters that serve to stimulate dopamine production. It is also able to synergize with dopamine as dopamine binds to the intermediate pituitary gland. More dopamine, means less ACTH release overall, which means less steroid production by the adrenal glands. SIDE EFFECTS OF ESPECIALLY LOW INCIDENCE WITH L-DEPRENYL USE (APPROXIMATELY 5% EXPERIENCED MINOR NAUSEA, RESTLESSNESS, OR REDUCED HEARING CAPACITY ) ADVANTAGES OF L-DEPRENYL OVER LYSODREN Because of the unique mechanism of this medication, Addison’s disease is not a concern and thus no monitoring tests are required with the use of L-Deprenyl. L-Deprenyl is the only medication approved by the FDA for the treatment of Cushing’s disease in the dog. ADVANTAGES OF LYSODREN OVER L-DEPRENYL L-Deprenyl is substantially more expensive than Lysodren. Approximately one dog in five with pituitary Cushing’s diseaqe will not respond to L-Deprenyl. The usual protocol if no response has been seen after two months of therapy is to double the dose and continue for one more month before determining the patient to be a non-responder and selecting another medication.
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