Cushing's with Renal Disease

Question: In early Oct. my 141/2 yr. old neutered male doxie was diagnosed w/Cushing's Disease. He had all the customary testing i.e. Dex suppression tests etc. and the test indicated Pituitary Dependent Cushing's. The vet elected to start him on Lysodren. He was admitted after finishing a 5 day course of this drug with vomiting and increased diarrhea-he also has colitis and hypothyroidism so some diarrhea was normal- but this was worse. The vet kept him on fluid therapy for 2 days before doing labs. On the second day he ordered a chem panel and found that his "kidney's were failing". This suprised me as his Bun was only slightly elevated before initiation of Lysodren therapy and his Creatinine had been normal. He kept him on fluid for another 48 hrs and his kidney values improved only slightly-BUN down to 112. He was discharged to my care on a low protein diet and PO4 binders. We repeated labs a week later and BUN was up to 128 and urine tests showed he wasn't concentrating his urine. I was told that Darcy was entering ESRD and that the prognosis was not good. My vet was opposed to giving subq fluid but as I work in a hospital and have access to the equipment and had friends with training help I started giving him 200ccs of fluid every other day. In addition, I started him on 5mgs of Pepcid in the morning. Initially he was very weak, thin and had lost a great deal of muscle. Very soon his appetite improved, he gained wt and got stronger. He went from 14.25lbs to 16lbs now. He's had labs repeated and on 11/1 is BUN was 128, 11/19 BUN was 56, 11/19 BUN was 56, 11/26 BUN was 57, 12/2 BUN was 59 and Creatinine was 1.7. His last labs were done on 12/30 and showed a BUN of 21 and a Creatinine of 1.2. Darcy did have a bout of pneumonia in November due, I believe, to aspiration of the liquid aluminum hydroxide I was giving him by syringe. He responded well to the antibiotics and his WBCs were normal on his last CBC. I have since found an aluminum hydroxide product in tablet form so I no longer risk using the liquid. I should also add that Darcy was started on Epogen because of low PCV. This has improved enough so that I have cut way back on the Epogen for fear of increasing his PCV too much too fast. My questions are:

When should I next have him tested? My vet is sometimes reluctant to do labs -and I don't need unnecessary expense-taking the leave well enough alone approach but Darcy's made such good progress I don't want to let anything realistically treatable slide. What is a responsible schedule for testing and rechecks while all is going well?

Is it possible that his kidney's were so "insulted" by the Lysodren that they failed but by so aggressively supporting them we've allowed them to recover? Could it be that this is not primary kidney disease after all and that if I get him through this he will no longer have kidney disease? I've read that kidney disease is not reversible and is always progressive. What could account for the improvement in his lab values?

What do I do about the Cushing's Disease? We've all but forgotten about that during the this time and I certainly don't want to put him thru any more Dex tests. Would Anipryl be risky? His hair has almost all come back since the Cushing's diagnosis and his water consumption and peeing are normal when you consider the subq fluid. He used to get me up 3-4 times per night to drink and pee and now usually sleeps thru the nite.

He's started itching lately. I know there are may possible causes but do you have any suggestions? The vet prescribed Atarax but that caused agitation and disorientation and I stopped it. He's on so many meds that I don't know how to distinguish between and allergic rxn and a skin disease. I don't see anything abnormal but there are some rough spots on his chest. I've read about a condition called calcinosis cutis-Darcy takes calcium carbonate on an alternating basis w/ the aluminum hydroxide as PO4 binders-could that be the cause? If it is ,is the condition dangerous?

Sorry for going on so long but I love this dog alot and have worked very hard to get him through this. I'm afraid I'll overlook something simple. I know he won't live forever but I do want him to have as much quality time as possible. Other than these recent catastrophes, he's been doing remarkably well and enjoying his life. Thanks for your help. Donna

Answer: Donna-

I think that there is a good chance that the kidney problems were due to the treatment for Cushing's disease. Approximately 5% of dogs treated with mitotane (Lysodren Rx) develop side effects consistent with hypoadrenocorticism (Addison's disease). This requires supplementation with either glucocorticoids or mineralocorticoid medications to prevent adverse effects, including kidney failure. If there was an Addisonian state induced by the use of mitotane there would be a good chance of recovery with fluid therapy and time, as the damage to the kidneys tends to fall more into the "one time insult" category rather than into a chronic progressive kidney disease category. As the adrenal glands recover from the effects of Lysodren over time, they will produce corticosteroids again in most, but not all, dogs. When this happens you will see the same signs that were present previously, such as increased drinking, increased urination, hair loss, thinning of the skin, muscular weakness, etc. It would be necessary to consider treatment again at that time. There is some chance that the current itchiness is due to calcinosis cutis, a secondary effect of Cushing's disease, but it would be good to rule out a secondary bacterial infection since there was a period when it is likely that your doxie's immune system wasn't working very well. If there was no response to antibiotics it may be necessary to think about administering corticosteroids. This seems really odd to think about in a patient suspected of having Cushing's disease, but it is not uncommon for suppressed allergies or other conditions responsive to corticosteroids to surface after treatment for Cushing's disease. The reason is that the dog was producing high levels of corticosteroids due to the disease, which was masking other symptoms. There would likely be a time when the symptoms would be suppressed again by natural recovery of the adrenal glands.

All of the above is based on the assumption that an Addisonian state was induced by therapy for Cushing's disease. The only way to really know if that happened is to do ACTH testing to determine if there is a response to the administration of ACTH. If a baseline blood sample is drawn, then ACTH administered (stimulates the adrenal gland) and blood drawn an hour later shows no response to the hormone, then it is very likely that the Lysodren completely wiped out the ability of the adrenal gland to produce cortisol, at least temporarily.

I understand why you might not want to do testing, especially now when things have improved so much. It would be necessary to do some type of testing prior to considering starting Lysodren again. It would be possible to start selegiline (Anipryl Rx) without further testing and to monitor clinical signs rather than lab values to assess success of therapy. At the present time the best study that I can find suggests that Anipryl is very effective in about 20% of the cases of hyperadrenocorticism and moderately effective in another 20%, so you would have to accept that the odds of success are less than 50%. You can always go back to Lysodren, or elect not to treat for Cushing's disease, if desired. If you do go back to Lysodren it would be probably be best to do ACTH testing shortly after starting treatment (maybe 72 hours) and then on frequent intervals until a maintenance dosage of Lysodren could be established. In any case, doing ACTH testing at the first sign of loss of appetite or vomiting would be a good idea.

I am hopeful that Darcy has continued to show progress in the kidney values and that it has not been necessary to administer Epogen (Rx) again. I am glad that you went ahead with fluid therapy, as it almost certainly helped in his recovery. I don't think it is necessary to continue the fluid therapy at this point if he has had another good test for kidney values (BUN < 30, Creatinine <1.5).

Mike Richards, DVM 2/2/2001

Cushing's and dog's death from Kidney failure

Question: My dog was started on Anipryl for Cushing's disease March 1998. He displayed many of the symptoms assoc. with the disease (excessive drinking and urinating). He had one blood test at that time which indicated that his liver enzymes were high. No other testing was done.

This past summer my dog had several UTI's and was treated with sulpha drugs. A blood test was taked in July because he was vomiting yellow bile. His kidney function was normal but his liver enzymes tested high. Determined the sulpha drugs were causing the vomiting and the medication was discontinued.

I had my dog back at the vet's the middle of Oct. 2000 because I thought his teeth were giving him problems (looked like he had a hard time chewing), sneezing a lot, had a runny nose, and was losing weight. I also mentioned to the vet that my dog would whine occasionally when he tried to lay down ( vet thought maybe arthritis). The vet checked his teeth, did not see any problems and gave my dog a polyflex inj. No blood work was done.

The end of November my dog was vomiting yellow bile on and off for days. He would eat then 8 to 12 hours later vomit bile, stools were normal, no diarrhea, still drinking water (not as much as he had in the past) and urinating (but it seemed to take him awhile before he would urinate). In the past several years he would vomit bile for a day or two then be fine. The vet examined him, thought it could be his liver and gave my dog a polyflex and depomed inj. No blood work done. Before he gave my dog the cortisone shot, I told the vet that my dog had had a bad reaction to the depomed shot he gave him a year ago for an ear infection. (My dog was very agitated, restless, and panting heavily after receiving the cortisone until he finally vomited 6 hours later 11/99.) I took my dog back to the vet the next day (11/29/00) because he was now vomiting brown bile and his food right back up after eating. He could also barely stand. The vet took a blood test and then started my dog on sub-Q fluids. The vet called that night to say his creatinine was high and that my dogs kidneys were failing. A second blood test was taken a week later in which his creatinine was still high. My dog was on sub-Q fluids at home for three weeks before he died. I made seven trips to the vet in that three week span. Two trips because I thought my dogs teeth were bothering him. It looked like he was having a hard time chewing. Toward the end I finally realized it was not the chewing food but the swallowing that was giving him problems (swollen glands?). The vet checked his teeth two different times did not see anything wrong but pulled several teeth and gave him more cortisone. I thought my dog was straining to have a bowel movement a few days before he died, the vet checked his rectum said there was blood in his stool but he was not backed up. I took my dog back the next day because he was still straining and the vet gave him an enema. My dog had a lot of blood in his stool. I now realize my dog was straining to urinate. He was drinking water and urinating until the very end, not much of an appetite though. What he ate he vomited right back up. During the time period that my dog was vomiting the yellow bile in November he would whine like he did back in October when trying to lay down (abdominal pain, stones, disc problems?).

My questions are the following: What do Cushing's dogs generally die of? Do you give Cushing patients more cortisone when their bodies already produce too much steriods? Could the cortisone have affected the blood test results causing an elevation in the creatinine level?(A blood test was not taken the first day I brought my dog in which makes me question its validity.) Do you treat kidney failure with cortisone? Does the cortisone make a dog bleed internally?(My dog did not have loose bloody stools before he received the depomed injection) Should my dog have been on IV fluids instead of sub-Q fluids if his creatinine was high and had kidney failure? What other factors could cause the creatinine to be high? What other conditions could cause my dog to vomit yellow bile? Could he have had a urinary tract blockage (urinary or kidney stones)? Should a urinary analysis have been done? Could my dog have had a tumor? What would swollen glands indicate?

Thanks, Susan

Answer: Susan-

It is likely that I am going to miss one of your questions in this answer, so please feel free to ask for additional clarification.

Cushing's disease causes a number of secondary problems in dogs. Recurrent urinary tract infections are not uncommon in dogs with Cushing's disease and some dogs with this symptom have urinary calculi (bladder stones or stones elsewhere in the urinary tract). Infections of the skin and gums are also possible as secondary problems due to immune suppression. Diabetes mellitus commonly occurs concurrently with Cushing's disease and they complicate each other. About 15% of dogs with Cushing's disease have adrenal gland tumors and some of these are malignant. Among the 85% of dogs who have pituitary-dependent Cushing's disease, about 20% will eventually develop large enough pituitary tumors to cause central nervous system disorders. Dogs with Cushing's disease frequently develop high blood pressure and an increase in blood clotting, which leads to kidney damage, heart damage and pulmonary embolisms. Gastrointestinal ulceration can occur when cortisol levels are high. Pancreatitis seems to be more common in patients with Cushing's disease based on our clinical experience. Since Cushing's disease is a geriatric onset disorder in most cases there are often times when another problem that was present causes death before the complications of Cushing's disease does.

If Cushing's disease is treated and the treatment is successful, some of the above problems are less likely, but other problems may occur. Some dogs have reactions to the medications used to treat hyperadrenocorticism and these are sometimes fatal. Once in a while, treating for Cushing's disease leads a sudden worsening of central nervous system signs in dogs. Because dogs with Cushing's disease are producing high levels of cortisol, this sometimes is masking another disease, especially skin disease and arthritis. Some dogs who are successfully treated for Cushing's disease will need care for these conditions and if it is difficult to achieve, there is a risk of euthanasia. Some veterinary clients will decide to euthanize their dogs due to the high cost of treating Cushing's disease or the inconvenience of returning for lab work repeatedly when mitotane (Lysodren Rx) is used as the treatment method, even though it is the most consistently effective treatment.

We try not to use cortisones in dogs with Cushing's disease, but there are times when a dog whose Cushing's disease is well controlled will need corticosteroid administration to treat other problems that occur. Selegiline (Anipryl Rx) does not suppress cortisol levels to the degree that mitotane does, so we try harder not to use corticosteroids in patients we are treating with this medication but we have when it seemed really necessary.

It is not likely that a single corticosteroid injection would cause kidney problems. Long term exposure to high dosages of corticosteroids can cause kidney problems through the development of high blood pressure and blood coagulation problems which can induce kidney disease. Corticosteroids do cause ulcers in some dogs and this could cause intestinal bleeding and it could cause vomiting. Long term vomiting can occur for a number of reasons, including gastrointestinal disease, liver disease, parasitism, kidney disease, chronic pancreatitis, cancer and central nervous system disorders. In dogs with Cushing's disease, several of these problems are likely to be present and they can occur independently of the Cushing's disease, as well.

One problem that occurs with some Cushing's disease patients is immune suppression, which might lead to enlargement of the submandibular lymph nodes. It is also possible that cancer was present in the oral cavity, which also leads to increased size of the submandibular lymph nodes.

Kidney damage occurs in many illnesses in which blood pressure gets low or blood pressure gets high and it can occur very quickly in the case of low blood pressure. This is not an uncommon problem when serious illness is present, especially in geriatric patients, which seems to be the case with your dog. It may have helped to use intravenous fluids rather than subcutaneous fluids if this was the case, but I do not know of a way to be sure of this.

When there are multiple problems present there is a tendency for one to lead to a worsening of another and for this process to continue to occur very quickly, leading to a situation in which the overall situation becomes overwhelming or at least seems that way. In a geriatric patient this occurs more quickly and when one of the problems becomes very severe there is a tendency among people making treatment decisions to give up and recommend euthanasia or to adopt strategies such as limiting pain and treating symptoms to keep patients as comfortable as possible but not fighting the problem all out, as might be done in a much younger patient with the prospect of recovery and a long life span, rather than recovery to the last previous level of health, which often was not very good. Age is not a decisive factor in this thinking, most of the time. The level of pre-existing disability is usually the decisive factor, especially when it is not clear that even that can be obtained with treatment. It really may have seemed obvious to your vet that your dog had no chance of return to an acceptable level of health. In that case, the real failure is not managing to communicate that to you in a way that you understood it. Sometimes I am not able to do that for clients, so I know that it can be a problem.

It is OK to ask long questions. Sometimes I miss some concerns in the long notes and if that has occurred, I will be happy to try to clarify whatever worries you.

Mike Richards, DVM 1/29/2001

Cushing's with renal disease

Q: Dear Dr. Mike: We are sorry to bother you with a second chapter about our 16-year old Dachshund Clea, who had been diagnosed with Cushing's in May. In our Aug. 30th message, we outlined the care we had been providing to her. Since that message was sent, we have done some further testing, and now have additional questions. On Wednesday, September 3, we did another blood test. Bun was 96.8 and creatinine 2.81. Because of the high bun reading, she was put on fluids iv for the day (about 6 hours). Alkaline phosphatase was 2791 and alt (sgpt) 231. These values seemed to have improved slightly but we were warned that they may reflect further loss of liver function rather than improvements. Glucose was 105.9 (normal reference range is shown to be 77.0 - 125.0). We also did a blood count, and it reported values in normal ranges except for the platelet count, which was high at 799 x 10^9/L (normal reference range is shown to be 175 - 500). Our vet told us that this was caused by the Cushing's, and by her kidney disease. We have also been told that one effect of Cushing's is to cause clotting, with a serious risk of pulmonary embolism, which makes inserting iv's risky. We had another blood profile done today (Sept. 8th) on her kidney values. Bun = 88.5 mg/dl; creatinine = 2.79 mg/dl. (Our vet decided not to put her on an iv today.) We also had her cortisol level tested on September 4th, and it was shown to be 7.1 mcg/dl (reference values: 1.0 - 4.5). We have continued to feed her with a syringe. Because of the high bun count we use only the NF and clinicare. Targets per day are 200cc of NF (pureed with water) and 100cc's of clinicare. She has seemed somewhat better than last week and more interested in her normal activities, albeit she is very weak and falls down occasionally. We have been giving her baytril injections im. Beginning August 6, injections were given twice daily of 1cc (her weight was then about 20 lbs). On August 19, on the advice of our vet, we began giving injections once daily (1.8 cc, her weight having declined to 18 lbs) and continued until this past Saturday (September 6), when we stopped. We have read the pharmaceutical information provided with the drug, and understand from that information that the normal course for baytril is ten days, and that it does have adverse side effects, including vomiting (it always had this effect on Clea when given as a tablet), and because of how it works, it should always be given in two doses, not as a single dose. That pharmaceutical information, however, warned that baytril can have an effect on clotting, and her high platelet count leaves us concerned. In reviewing our records, we noted that the vomiting episode which caused us so much worry in late July, early August coincided with the administration of the baytril. At that time, she had high bacterial count in her urine and apparent infections elsewhere, so use of baytril made sense. Now, because of our concern about her appetite, the condition of her liver and the platelet count, we decided to stop administering the baytril until we had more information and could make an informed judgment about the wisdom of this treatment.

On Sept. 6th, the day we discontinued the baytril injections, her appetite seemed to have returned, at least partially; she has eaten a little solid food on her own (for the 1st time in over a month), mostly of the high protein foods she likes so much (sliced roast beef from the delicatessen, and some canned dog food, baked chicken and rice (about 1/3 cup total of the combined foods)). Perhaps, the baytril was a factor in suppressing her appetite? She now weighs 17.6 lbs. What do you suggest about the baytril? Were we wrong to have administered it as we did for nearly a month, especially since she was on augmentin 21 days before that time? Should we use it as a preventative, or does that do more harm than good? It seemed a bit odd that the reason we were told not to use tagamet to help with Clea's digestion is the inability of the liver to break it down, yet doesn't breakdown of baytril in the body use the same system? And what do you suggest about the platelet problem? Our vet said something about aspirin, but what do you recommend? Will we have to continue to put Clea on iv's from time to time to help with the kidney disease? Because she has begun eating a little on her own, we have slowed down the syringe feeding, which she fights vigorously. She seems hungry, but the foods she nibbles are all high in protein.

Should we put her back on lysodren in an effort to control the Cushing's even though her appetite is so poor? Should we consider half the previously prescribed dose (that is, 250 mg daily instead of 500 mg)? Do you think that would be a good idea considering her kidney problem? (Our questions and concerns about the effect of the lysodren therapy, possible overdose before she reached her maintenance level on lysodren, etc., were sent to you in our earlier message, so we won't repeat them again here.) Clea does really pretty well considering the illness and her age. She sleeps most of the day, but when she is awake she is alert and mobile (though weak and lame--her hindquarters give out every now and then). This past week, she has started barking again, with demands to go outside. She is alert to activities outside in her yard, and will sit before the screen door and watch for squirrels. Her breathing is easy and not labored, both when she is at rest and when she is active. (We have noticed occasional tremors in the past few days.) She is not experiencing any discomfort, let alone pain despite the weakness, so we still hope that there is something we can do for her. Well, this is a long list of problems, and the message got a bit longer than we meant it to. But we love this little dog dearly, and we really would appreciate any advice you can offer us. Many thanks. Tom and Maria

A: Tom and Maria-

We have used Baytril for long time periods when it seemed necessary. So far, it seems to cause less side effects than many antibiotics but that doesn't mean it couldn't be the cause of vomiting or inappetance in Clea. I am not sure I followed the rationale for antibiotic therapy but as you may have figured out we get a lot of email and it is difficult to keep track of individual cases.

I think I'd consider the use of one of the alternative therapies for Cushing's disease. Deprenyl is approved for this purpose now and ketaconazole is used for control of Cushing's as well. Both therapies are reported to be a little more expensive than mitotane (Lysodren Rx) therapy but that doesn't seem to be a major concern on your part. These products seem to have a little more safety margin than Lysodren. You might want to ask your vet about this.

I don't think I'd be too concerned about the platelet levels. Aspirin will deactivate platelet function but does not decrease platelet numbers, as far as I know. I do not think it would be harmful to use aspirin unless it caused gastrointestinal upset but I wouldn't be overly concerned about the possibility of clotting, personally. Perhaps your vet has a bad experience with this that I have managed to miss in my practice but so far, this has not been a big problem in our Cushing's patients, to the best of my knowledge and memory.

Monitoring the renal disease is important and continuing to treat symptoms of problems is a good idea. In complicated cases of hormonal disease it can be helpful to consider consulting with an endocrinologist or internal medicine specialist. Dr. Chiapella in Manassas is very good and the vets at the veterinary school at Blacksburg are also a good choice. This is not always necessary but when I am struggling with a case I like to get a second opinion on it --- even if I'm doing the best that can be done it is reassuring to hear that for the owner.

Good luck with this.

Mike Richards, DVM

Cushing's amended answer

Q: Your Q&A site was recommended to us by Leslie, whose dog also has Cushing's. We have a number of questions, and apologize for the length of the explanation. Our dog (Cleopatra = "Clea") is a 16 year old (this month) longhaired dachshund who was diagnosed with Cushing's in May (dexamethasone suppression test give May 15). We had taken her to our vet because of persistent weakness, quite noticeable in an otherwise active dog. She had also begun to drink and urinate profusely, and had a huge appetite. On a blood panel done a week earlier, her liver enzymes were elevated, but the test was otherwise normal. On that test, the initial cortisol reading was 6.6 mcg/dl, and the reading was elevated to 29.0 and 22.8 at 5 and 8 hours. She went absolutely flat after the test, and took about a week to recover. Because we had been unsuccessful with lysodren on two prior occasions in treating dogs with Cushing's, we tried to treat her condition with Eldepryl (Anipryl). The drug was available only in human form (for Parkinson's). Beginning May 20, we administered 1 5mg capsule once a day until May 28, when we began administering 2 5mg capsules once a day, until a second dexamethasone suppression test was done July 14th. The readings for this test were 6.0 pre administration and 14.0 and 16.5 at the 5 and 8 hour marks. Again, Clea seemed to suffer greatly from this test. He told us that the drug had slightly changed the level of cortisol in her system, but not enough and recommended that we increase the dosage to the test dosage (4 5mg capsules once a day). We did try, but Clea is very resistant to taking pills, and the capsules are quite large, unsuitable for administration to a dog. A blood panel also done at this time disclosed that Clea's urea nitrogen had greatly increased, from 38 MG/DL in May to 92 on July 14. Creatinine was 1.8 then, still in the range of normal (although her liver values were greatly elevated). This was diagnosed as a bladder and/or kidney infection. The bladder infection was confirmed by urine tests and a culture. We treated this with a liquid antibiotic called "augmentin." On July 22, we had a sonogram done, and this test reported a large adrenal tumor. Clea's liver was enlarged and opaque (as would be expected from Cushing's), and some indication of kidney deterioration. On the preceding Friday, Clea had tried to navigate a flight of stairs, but had fallen all the way to the bottom. Examination for possible injury in this situation, seemed to show only mild aggravation of an old lower back injury, but we wonder about that. In any event, she was by this time very weak, and with her liver and kidney problems, we decided against surgery. (One of the Cushing's dogs we had previously owned had had this surgery, but then had never gotten to his feet again. He died within a month from pneumonia. With an old dog, who had been weakened from the effect of the Cushing's, and who had a bunch of other problems, surgery seemed to be a poor choice.) Instead, we began to treat with lysodren (1/2 500mg tablet twice a day), as our vet recommended. These pills are dreadful. We were told that lysodren could be compounded and presented in liquid form at the required dosage, but we were never able to find someone who could do that. By the time of the sonogram, Clea's appetite (which had been very good up to that point) tapered off, and by the end of the month, ahe was not eating at all. We began to administer Lysodren on July 27 (250mg, twice a day), although the information we had available to us then indicated that an adrenal tumor is very resistant to treatment with lysodren. An ACTH stimulation test given Aug. 6 showed that we had made some progress (pre test value reported as 2.0; post 2 hours, 7.8), and our vet advised us to increase the Lysodren dose. But Clea's kidney values had worsened (a blood test on that day showed urea nitrogen at 106.1 and creatinine at 2.63), she had stopped eating (and drinking by that point) and had begun vomiting. We were told that the vomiting was brought on by the deterioration of her kidneys (and probably other organs as well, particularly the liver). On August 10, we took her to the emergency room because of the vomiting. She was on iv fluids for about 2 days, and her kidney values improved (urea nitrogen from 107 (when admitted) to 51.3, Creatinine from 4.5 to 2.5), and the vomiting stopped. We also stopped giving her lysodren. When she came home with us, we began giving her baytril by intramuscular injection (1.8 cc once a day) to control the infections. Since August 13, we have fed Clea by syringe (with Clinicare, a Veterinary product like Ensure, and with pureed dietary foods such as "EN-Formula" (easy on the digestive system after vomiting and diarrhea episodes) and more recently "NF-Formula" (said to be easy on the kidneys)(both processed by Purina CNM and available by prescription through the Vet's office)), but she has shown no interest in eating solid food on her own, not even her most favorite foods, although she has taken a bite or two, here and there. In the past couple of days, we have added small quantities of pureed egg noodles for calories (with a couple of pureed boiled chicken livers). On August 20 and 21, we profused her kidneys a second time, reducing the Urea Nitrogen to 43.5 and the Creatinine to 1.96 (normal being reported as [7-27] and [.50-1.80] respectively), but still she will not eat. A blood test administered last week (August 27), showed her urea nitrogen at 49 and creatinine at 2.6 (Alkaline phosphatase was shown at 2800 U/L and ALT (SGPT) at 385, about where these values have been for the better part of three months). We were alarmed when glucose was shown at 23 MG/DL, a large drop-off from the last time this value was tested (on Aug. 19), when it was 99.1. This was explained to us as the effect of allowing the blood sample to sit before being sent to the lab. But we have never seen this before, even in blood samples handled in the same way, so it is alarming. Clea is also noticeably weaker, and her eyes are a little red. She drinks water on her own and appears interested in her food bowl but just won't eat. Her weight has declined over three weeks from 20.2 lbs to 17.8 lbs.

We have a number of questions, which boil down to how to proceed. What can we do about her refusal to eat? Is there a better diet for her present condition? Would it hurt her to feed her the chicken livers (and gizzards) which she likes? Is it possible that this situation has been brought on or aggravated by a rapid decline in the cortisol levels in her system, even though she had reached her maintenance level? If so, would administration of prednisolone help her? The low dose dex suppression test made her go flat when it was done in July. Would it be helpful to try lysodren again, even though she is not eating? Is there a protocol for renal insufficiency that we can follow for her? Thanks for considering Clea's case. It took a while to set it out, but we wanted you to know as much as we could tell you. Any suggestions would be most appreciated. Tom and Maria

A: Tom-

I didn't realize you had tried l-deprenyl when I sent the previous message. It will only work in pituitary dependent Cushing's disease so it is not surprising that it did not work well with an adrenal tumor present. Ketaconazole may alleviate the cushingoid effects of the tumor but will not stop the progression of the cancer so it is also a questionable choice. I can understand not wanting to do surgery for adrenal gland tumors, especially in an already compromised patient, but that is sometime to consider, as you know. Lysodren at dosages high enough to totally destroy the adrenal tissue has been advocated for treatment of adrenal gland tumors, as well. This does produce the opposite problem, hypoadrenocorticism or Addison's disease, and it is necessary to treat for this with appropriate medications, including Florinef (Rx) and possibly prednisone.

I think that I would be more worried about hypertension associated with the Cushing's disease leading to the secondary effects on the kidneys and possibly causing some of the other observed symptoms but I may not be aware of some detail of the case that makes your vets suspicious of this. Spread of the adrenal tumor to the kidneys is also possible and may be a contributing factor in their problems. Most vets are still not equipped to accurately measure blood pressure due to the cost of equipment and the learning curve associated with use of it.

It is acceptable to crush the Lysodren and load the powder into smaller gelatin capsules available at some pharmacies (you might have to search for one or ask the pharmacist or your vet to order them for you). This usually means giving a higher number of capsules than than the number of pills you were giving but the smaller size may make it more acceptable, anyway.

Do consider asking for referral to an internal medicine specialist. I think that Cleopatra sounds like a patient with a very complicated case of Cushing's disease and it is often best to seek the help of someone who deals with the most complicated cases on a more routine basis.

Mike Richards, DVM