Multi Symptom Disorder or Multiple Disorder problems


Neurologic signs with Cushing's and other disorders

Question: Dear Dr. Mike: My 12-year-old schnauzer Delaney was diagnosed with pituitary-dependent Cushings about a year ago. He also has heart disease and kidney disease, and has had several bouts with pancreatitis since he was one year old. My vet and I have been able to successfully manage all of these problems with regular medications and regular blood testing (about every 3 or 4 months)--until now. In the past month, Delaney has lost 2 pounds (he is down to 15 pounds) and has been vomiting occasionally. The only food he can keep down is canned NF--he has been on WD all of his life, so he is very muscular and slim. (He is still very hungry when I feed him. He has four meals a day, about 1-1/3 cans per day.) He seems more nervous or anxious than usual and has trouble getting comfortable, and his body quivers frequently, even when at rest. (I have noticed the quivering, particularly of his hind legs, for the past couple of years.) He has also recently developed a urine drip, which bothers him tremendously and causes him to lick himself. (My vet did prescribe phenylpropanolan, but he doesn't tolerate it and vomits.) Delaney has had complete blood workups in the past month, and the only abnormalities are a slightly elevated amylase (1689) and glucose (158). He had a full-body ultrasound, which showed that his heart disease has not worsened and that one of his kidneys shows "mineral deposits" and is smaller than normal. The other kidney appeared normal. His pancreas also appeared normal. My vet indicated that his adrenal gland appeared to be a bit larger than he had hoped, but since he had just run an ACTH test two months ago and it was in the correct range, he would not address that at the present time and concentrate on the existing problem. The radiologist found no existence of tumors, although Delaney has many fatty (liquid-filled) tumors all over his body, which my vet says are not a problem.

That leaves us with the problem of determining what is going on now. Why is Delaney vomiting and losing weight? Why is his body weakening and the quivering increasing? Do you suspect that something else may be going on, i.e., cancer, etc., or are these symptoms the result of one or all of his current diseases? (I have read the 1999 article on Cushings, in addition to many other resources on the subject.) In all of my research, I have never found a good definition of "neurological symptoms." What, specifically, are they? Is there any way to reverse them?

Delaney is my constant companion and soulmate. If there is anything I can do to prolong a quality life for him, I will do it. I will appreciate any insight you can provide. By the way, I do trust my vet totally--I have been trusting him for 16 years with my animal companions--but realize the value of input from other sources. He fully agrees.

Thank you for your assistance. Best wishes, Sharon

Answer: Sharon-

I think that you are right about finding descriptions for neurologic signs when this is mentioned as a possibility. The problem with neurologic signs is that they can be almost anything because the nervous system controls most of the functions in the body. Among the possibilities for neurologic signs are weakness, tremoring, paralysis, blindness, head pressing, confusion, seizures, balance problems, behavioral changes, depression and loss of senses such as touch, smell, taste, hearing. There are probably a number of other neurologic signs that I am forgetting, but the basic situation is that very many problems can be due to neurologic damage, so if there is no evidence for a physical cause for a problem it might be a neurologic problem. In Cushing's disease the most common neurologic signs that occur are tremoring, weakness (which is also muscular in this case) and seizures. It is possible for vomiting to occur due to neurologic disorders, especially ones that cause increased pressure on the brain or disturbances in balance.

We have patients who seem to experience gradual weight loss when we treat them for Cushing's disease. We have always assumed that this was due to a decrease in cortisol levels which lowers the tendency for the patient to have an increased appetite and weight gain. However, Cushing's disease is most often caused by cancer of the pituitary gland or cancer of the adrenal gland. When the cancer affects the pituitary gland it can become large enough to cause problems, including weight loss and the neurologic signs mentioned above. It is hard to say if this is happening without an MRI examination. I am not aware of a veterinarian in the US who is actively pursuing removal of pituitary tumors as a solution to Cushing's disease but this is an available option in the Netherlands as it is done at Utrecht.

Many older dogs have tremoring in the rear limbs, so this may be just an effect of aging and not related to the Cushing's disease. In addition, many dogs with Cushing's disease have muscular weakness which could also contribute to muscle weakness and tremors. There are probably some dogs whose ability to regulate body heat is adversely affected by having Cushing's disease as well.

It would probably be OK to feed Delaney more. I think that I would probably advise that in this situation for a client of mine but since your vet is more familiar with the pancreatitis history it would be best to ask him or her about this.

Vomiting can be caused by a number of illnesses so it is a very non-specific sign. Many of the potential possibilities can be ruled out by normal serum chemistry findings when lab work is done and I think it is reasonable to assume that they aren't present since Delaney has had lab work recently. If the intestines didn't seem thickened when the ultrasound examination was done the potential for the vomiting to be a sign of inflammatory bowel disease (IBD) is lessened but the history of chronic pancreatitis still makes this something to think about. It would be a good idea to review the medications that you are using since there are multiple problems and to try to be sure that one of them isn't a possible cause of the vomiting --- or that interference between two of them isn't contributing. Some dogs with Cushing's disease and/or chronic pancreatitis develop gastrointestinal irritation or ulcers that might contribute to vomiting, as well. This is also true of dogs with kidney disease. Using a medication to protect the GI tract, such as cimetidine (Tagamet Rx) or related drugs may be helpful. I know this is a frustrating problem and I hope that it has already been resolved. Vomiting can sometimes occur in patients being treated for Cushing's disease when the dosage of mitotane is too high and is causing hypoadrenocorticism (Addison's disease). This is probably more common early in the use of mitotane but it still has to be kept in mind when vomiting occurs in patients being treated with mitotane. If this is the cause then administering physiologic dosages (about 0.2mg/kg per day) of prednisone or prednisolone should resolve the signs.

Incontinence can be due to neurologic disease, as well. If this is the case, medications directed at the neurologic problem present can be helpful. There is a small possibility of detrussor atony associated with Cushing's disease and this might respond to administration of bethanecol. This isn't very likely, though.

Dogs with Cushing's disease frequently have urinary tract infections and this may cause symptoms that resemble incontinence, or even cause incontinence. It is always worth considering this possibility when any urinary tract problem occurs in a dog with Cushing's disease. For some reason, even good control of Cushing's disease won't always lessen the incidence of secondary urinary tract infections in some patients. Culturing urine obtained by cystocentesis is the best way to rule out bacterial urinary tract infections. Cystocentesis is the process of obtaining urine by sticking a needle into the bladder to get the urine. This is not as hard to do as it sounds. Most dogs don't seem to mind this any more than drawing blood.

Male dogs will sometimes respond to testosterone supplementation when they have incontinence when they won't respond to phenylpropanolamine.

I can't tell from your note how you are treating the Cushing's disease but we have tried both selegiline (Anipryl Rx) and mitotane (Lysodren Rx) in a couple of dogs now, hoping to lower the dosage of mitotane when we thought it might be causing side effects. We haven't caused any problems that we have been able to see, yet. The combination seems to make our patients feel better than when we use mitotane alone, but that is a very subjective observation.

I hope this helps some.

Mike Richards, DVM 12/21/2001

Some Cushing's with Addison's questions


I think from reading your note that you had several questions about Cushing's disease.

Question: 1) Why was a diagnosis of Cushing's disease made, treatment started and then treatment for Addison's disease initiated after this treatment and what is the difference between Florinef (Rx) and DOCP?

Answer: The treatment of Cushing's disease (hyperadrenocorticism) with mitotane (Lysodren Rx) sometimes results in the total destruction of the adrenal glands. When this happens, the result is artificial creation of a different condition, Addison's disease (hypoadrenocorticism). Some veterinarians think this is the best outcome for Cushing's disease but this is debatable. In any case, when it happens, it is usually possible to treat successfully for the Addison's disease.

There are two ways to replace the mineralocorticoids that are deficient in Addison's disease. The first one is to use fludrocortisone (Florinef Rx). Fludrocortisone dosage is variable and often has to be increased over time. The second therapy is to use deoxycorticosterone pivulate ( DOCP, Percorten V, Rx), which is a long acting injection that usually lasts 25 days, but may vary in effectiveness from 21 days to as long as 35 days. Checking sodium and potassium levels and the ratio between them can help in establishing the duration of action for this medication. It is probably a good idea to check these electrolytes at weekly intervals when first starting to use DOCP. Fludrocortisone is expensive and the dosage levels necessary can get pretty high, with some dogs requiring as many as ten tablets daily. There are compounding pharmacies that can make it less expensively, but quality has been reported to vary some among the preparations, so this source must be used with caution. DOCP is less expensive most of the time and usually provides good control.

Side effects of DOCP therapy include increased drinking and urinating, diarrhea, vomiting, loss of appetite and high sodium/low potassium levels (opposite of the levels expected with Addison's disease). These are pretty similar side effects to Addison's disease itself, so both a reaction to the medication and inadequate control of the Addison's disease by the medication have to be considered. Checking electrolyte levels can help in determining which problem is occurring. It should be noted that slight irregularities in electrolyte levels at the end of the period between injections is considered to be acceptable.

Question: 2) Does prednisone cause diarrhea when used at the dosages necessary to treat Addison's disease?

Answer: Prednisone does not cause diarrhea at physiologic levels (0.2 to 0.4 mg/kg per day) very often. It is more likely that the DOCP is the cause or that the Addison's disease is not adequately controlled at this time. I

Question: 3) How do I treat the diarrhea without affecting the Cushing's disease or Addison's disease?

Answer: The first step is to try to be sure that the Addison's disease is controlled by monitoring electrolytes. Since there was an initial diagnosis of Cushing's disease it is also conceivable that the adrenal glands could recover and that Cushing's disease could return, causing further complications. So monitoring for this possibility, perhaps through the use of ACTH response testing, would also be a good idea.

Question: 4) Are there dietary changes or dietary supplements that might help a dog with either Cushing's disease or Addison's disease?

Answer: It is probably best to try to feed high quality protein diets that are not excessively high protein quantity diets for patients with Addison's disease. It may also be beneficial to supplement salt intake in Addison patients. A good quality regular dog food sprinkled with a little table salt is probably adequate.

Cushing's disease patients probably do better with lower salt diets and may benefit from low fat, moderate fiber diets, both for weight control and to aid in preventing hyperglycemia (high blood sugar) that occurs in some Cushing's disease patients.

Since the dietary requirements are different for Cushing's disease and for Addison's disease, it really is necessary to keep monitoring for the return of Cushing's disease so that medication and diet adjustments can be made as necessary.

I hope that this information answers your questions. Please feel free to write for clarification if necessary.

Mike Richards, DVM 8/27/2001

Diagnosing Cushing's and hypothyroidism

Question: Dr. Richards,

I am a new subscriber and have been reading your ques/answers for a couple of weeks now. I am really impressed with the personal and in-depth information you provide. We have a twelve and a half year old pet, half German Shepherd half Golden Retriever, Princey by name. Princey has always been healthy with few health problems. Since the last few months, he has been drinking and urinating excessively. He has become almost completely bald at the collar area and has lost a lot of hair around his stomach area and a patch on his back, a little above his tail. His skin is dry and flaky, like dandruff. On the back area, near his tail where he has lost hair he has little raised bumps. We took him to his regular vet a few times but he said it was just old age, he took some x-rays as Princey's back legs seem to be bothering him, it takes him longer to get up. X-Rays showed slight arthritis. Around the middle of March, he was given steroids for two weeks and an aspirin a day. He finished his course of steroids and was on aspirin until April 20th. We have given him aspirin only twice after that. I don't like to put him on any medication until I am sure it is necessary and will not harm him but at the same time want to make sure he gets whatever he needs to get better. After reading your columns, we took Princey to a different vet on May 7th, as I was afraid Princey showed all the classic signs of Cushings. The new vet who seems to know a lot about Cushings, unlike the first one, examined Princey and did a urine and blood test. The urine test had a reading of one, which she said was very dilute but showed no trace of diabetes. The blood test, the vet said shows no sign of Cushings, she has asked we do a water deprivation test to rule out diabetes insipidus. She also said his thyroid levels are low and that could be causing the hair loss and skin problems and that we could put him on a thyroid supplement if his hair loss is bothering us but that it is not absolutely necessary at his age. Your column says though that sometimes blood tests are inconclusive for cushings. Also, will it hurt to put him on thyroxine if that really is not the problem? Does it have any side effects? Will it aggravate any other condition he might have, like Cushings or diabetes insipidus? Do you think we should push for more testing to rule out cushings? Is there any kind of skin test we can do? Dr. advised us to put aloe on his skin. His blood test results were all within the normal range except for these -

neutrophils 84 (normal 60 - 77),

lymphocytes 6 (normal 12 - 30),

lymphocytes absolute 570 (normal 690 - 4500),

alk phos 199 (normal 5 - 131),

GGT 24 (normal 1 - 12),

cholesterol 360 (normal 92 - 324),

BUN 10 (normal 6 -25),

creatinine 0.5 (normal 0.5 - 1.6),

BUN/Creat ratio 20 (normal 4 -27),

T4 RIA 0.42 (normal 1.0 - 4.0),

FREE T4 (RIA) 0.38 (normal 0.65 - 3.00),

uantitative platelets 448 (normal 70 - 400).

His AST(SGOT) was 29 and ALT (SGPT) was 70. The vet said his results were all okay for his age and that if he had cushings his alk phos levels would be markedly higher. Any input from you will be greatly appreciated as I am very worried about Princey and would like to get him back to his old self as soon as possible. Thank you, padma

Answer: Padma-

There are a lot of things to consider with the information that you have so far.

It is not possible to diagnose hyperadrenocorticism (Cushing's disease) based on the results of a standard blood chemistry examination nor is it possible to rule it out based on these results. It is true that many dogs with Cushing's disease have elevations in the alkaline phosphatase levels in their serum, but many do not, as well. It is necessary to do some sort of specific testing in order to try to rule in or rule out the Cushing's disease. The most commonly recommended test is a low dose dexamethasone suppression test (LDDS). This test takes most of a day to run. A blood sample is drawn early in the morning and immediately afterwards dexamethasone is administered intravenously. In four hours a second blood sample is drawn and after 8 hours a third blood sample is drawn. The cortisol levels of the samples are compared. If Cushing's disease is not present, the cortisol levels should go from normal levels to very low levels (they are suppressed). If Cushing's is not present, the cortisol levels remain high after the injection of the dexamethasone. An alternate test is the ACTH response test. This test is less sensitive to the presence of Cushing's disease but can be run much more quickly, making it more convenient at times. To do an ACTH response test, a blood sample is drawn any time during the day and then a hormone, adrenocorticotropin (ACTH) is administered. An hour later (two for some ACTH preparations) a second blood sample is drawn. If the results of the second sample show markedly elevated levels of cortisol, it indicates that Cushing's disease is present. There are other tests that help to determine what type of Cushing's disease is present but one of these two tests is a good idea to determine if Cushing's disease is present.

It is pretty important to know if Cushing's disease is present, prior to trying to decide if hypothyroidism is actually present. The reason for this is that the presence of almost any other disease can cause the thyroid levels in the blood stream to drop. Therefore, it is hard to test accurately for hypothyroidism in a patient who has a problem like Cushing's disease. If Cushing's disease is present and can be treated for, then it is possible to more accurately test for hypothyroidism. In some cases, especially when there is only a partial response to treatment for Cushing's disease, it may be necessary to go ahead and treat for hypothyroidism without being certain if it is present. Fortunately, it is relatively safe to supplement thyroxine in a dog, even if they don't actually have hypothyroidism. It is better to work to be sure that a life long supplement is necessary before giving it, whenever possible, though. Hypothyroidism can cause increased drinking and increased urination in some patients and the hair loss can also occur with either disease, so it is entirely possible it is present and that it is the sole problem, but increased drinking and urinating are much more common with hyperadrenocorticism.

I sometimes have a hard time asking a patient to spend money on Cushing's disease tests because in our practice, I am pretty sure that of the dogs I test, only about 25% of them actually have Cushing's disease and the tests only help determine one thing -- if Cushing's disease is present or not. However, since there isn't any other way to determine if the disease is present and since it is important to both the dogs that have it and those that don't to know what is going on, I know that it is necessary to do the testing. I really do think that I would want to know if Cushing's disease was present with the clinical symptoms that Princey has. So I do recommend asking your vet about further testing.

Good luck with this.

Mike Richards, DVM 5/15/2001

Cushing's with heart enlargement in Doxie - chronic cough

Question: Dear Dr. Mike,

I wrote to you in February regarding my mini doxie Wizzo. At that time her vets were trying to determine if she had Cushing's disease. Since then they have confirmed Cushing's, started Lysodren, which she responded to beautifully based on the ACTH stim tests, and now have her on a weekly maintenance dose. Unfortunately, she continued to be weak and listless so the doctor did an x-ray and discovered that Wizzo had a "slight" heart enlargement. She was put on Vasotec and Lasix. The Lasix has since been discontinued. Throughout all this she has had a persistent cough, some days worse than others. She was not regaining any strength and showed no interest in doing anything but lying by me or my husband. She was then started on Tussigon and Tribrissen. She seemed to be improving, but after she completed the Tribrissen her cough intensified and the listlessness returned. Rather than put her back on the Tribrissen, her vet put her on Baytril. When she showed no improvement after 4 days, we took her back to the vet. He stopped the Baytril, resumed the Tribrissen, and put her on Prednisone 5mg on 5/3. 5/5, and 5/7. Finally, something worked. Her cough stopped and she started to act like her old self again. However, since the Prednisone is stopped, her cough is coming back. She is still on Tribrissen and Vasotec and gets Tussigon 1/4 tab 2x a day (any more than that makes her too drowsy). I spoke to her vet by phone, and he said if her cough continues to worsen again, she will have to be x-rayed again. He did not venture what else may need to be done.

I realize that medicine is not an exact science, but I'm concerned that there seems to be so much trial and error involved in her treatment. What would be the customary course of action at this point? Could she be kept on a low dose of Prednisone if that is working? Would that interfere with her Lysodren tx? Her doctors tend to go with the cheapest and easiest course of action, though I have assured thaem that my primary concern is getting Wizzo stabilized. I am so appreciative of this web site. I find it so reassuring to be able to find additional up-to-date information about Wizzo's problems. Thank you. Donna

Answer: Donna-

It is always difficult for me to figure out what to do when I have a patient who has Cushing's disease but also has a problem that responds well to the use of corticosteroids. There seem to be two choices in this circumstance.

One consideration would be to try to back off a little on the regulation of the Cushing's disease and let the natural cortisol levels rise, since that is what happens with Cushing's disease, to see if that would allow resolution of the problem without using additional medication. The problems with this approach is that it is know what level of cortisol to try to regulate to and that when administering Lysodren there will be ups and downs in the cortisol levels based on when the Lysodren is given.

The other approach is to regulate the Cushing's disease using the standard testing and then to add prednisone to achieve the desired therapeutic result, in this case a decrease in the coughing. This is the approach to this problem that we usually take. The problem with this approach is that prednisone use does interfere with the ACTH response test, which is the test usually used to evaluate the response to Lysodren. I haven't quite figured out an exact way to make adjustments for the effect of prednisone but we haven't gotten into trouble that I am aware of doing this, probably because the prednisone supplementation helps protect against the effects of Lysodren overdosage, if we are sometimes using too much Lysodren.

A third approach to this problem would be to administered sufficient quantities of Lysodren to completely wipe out the adrenal glands and then treat for hypoadrenocorticism (Addison's disease). The complications with this approach are that hypoadrenocorticism is more likely to be life threatening than hyperadrenocorticism and so it is important that the pet's caretaker really understand the importance of the medications. The advantage is that the physiologically appropriate dosage of prednisone has been established, so as long as control of the secondary problem (coughing) requires at least that dosage there should be no problem with glucocorticoid levels. It is still necessary to also supplement a mineralocorticoid product such as Florinaf (Rx), in addition to prednisone or another glucocorticoid.

I suspect that the absolute best approach to each patient probably varies from one to another, but we tend to use Lysodren and prednisone at the same time and try to balance the dosages when we must deal with a need for cortisone supplementation in a patient being treated for Cushing's disease.

It would be helpful, if possible, to be sure that the prednisone was necessary. The two conditions that lead to chronic coughing that are most responsive to the use of corticosteroids are collapsing tracheas and chronic allergic bronchitis, in dogs. Both of these conditions usually respond better to prednisone than to antibiotics and often respond better to prednisone than to cough suppressants. Collapsing trachea problems often show up on X-rays but can be definitively diagnosed by endoscopic examination of the trachea. Allergic bronchitis is hard to diagnose with certainty but trachea wash or bronchoalveolar lavage may allow a tentative diagnosis with strong evidence to support it. This testing also allows for culture of whatever bacteria are found, which can help in the choice of antibiotics if they seem necessary. Most veterinary practices can do tracheal wash procedures but may be uncomfortable evaluating the results and most veterinary practices probably don't have endscopes at this point. We refer our patients to an internal medicine specialist for endoscopic examinations. Your vet may be willing to do this, too.

Good luck with this. If you have further questions or are confused by the information in this note, please feel free to ask for clarification.

Mike Richards, DVM 5/15/2001

Hypothyroidism and Atherosclerosis

Question: Hi Dr Mike,

Jake my 7 yr. old Shepherd / Husky has just been diagnosed with Hypothyroid and clogged arteries mainly the aorta. He had ultrasonography and the vet said he had never seen anything like it and the prognosis is grim.

Here's how it started 6 months ago: * Weakness in the hind quarters, at times he couldn't walk he was thought to have Myasthenia Gravis. * Stiff hind legs * General lethargy and depression * Skin inflammation and hair loss * Trembling * Severe vomiting * Anorexia * Weight loss (10 lb.) * Some muscle loss * Arrhythmia (rapid) * Weak pulse

I rushed him to the emergency clinic when the vomiting started and the vet did many diagnostic tests: CBC, WBC, Chem 7, urinalysis, and most were normal except: ALKP 222 BUN 29.4 CREA 2.66 but his cholesterol was 1018.6 !!!

The internist that did the ultrasound the following week prescribed: ~ Soloxine ~ Adult dose fish oil ~ Science Diet R/D ~ Mevacor I've added 1,000 IU vitamin E, lecithin, oatmeal, garlic, 1 enteric aspirin and Pepto Bismol or Pepcid AC The problem is he is still vomiting at night and I worry that he will continue to lose weight and or muscle and the meds won't work! My question is why is he vomiting so much??? And is there anything else I can do? Can plaque be reversed? Is there a treatment available (I e-mailed a vascular site to you) Is he at risk for heart attack or Angina pain? It's so rare no one seems to know...Please help!

Thank you for your time, Jake & Lisa

PS. We live in Maine about 4 hour from Tufts Univ. I know they probably can't do angioplasty but do think they could do anything?

Answer: Jake and Lisa-

There are reports of severe alterations in lipid metabolism in some dogs with kidney failure. Since the creatinine level is high enough to suspect that kidney disease is present, this is something to consider. There is an article on this in the Dec 1, 1999 issue of the AVMA Journal. In this article the authors (Bauer, JE; Markwell PJ, et al.) suggested that there is a benefit to using cholesterol control medications in dogs, although the research was done with rats. Kidney problems would be likely to cause vomiting if they continue to be present. Unfortunately, atherosclerosis is rare enough in dogs that I can not recall seeing a dog with this condition and do not have enough experience to tell you if vomiting is a common problem in patients with this condition.

When atherosclerosis is associated with hypothyroidism, treatment of the hypothyroidism and use of a restricted fat diet has been shown to reverse some of the atherosclerotic lesions (Compendium of Continuing Education, Sept. 1995, Zeiss and Waddle).

The internist has taken the steps recommended in the articles above to try to control the situation, along with current recommendations to use fish oils.

I would be worried by the use of aspirin in a patient with chronic vomiting and would encourage the use of famotidine (Pepcid AC tm). I can understand the desire to use aspirin given the overall situation but it just worries me when GI signs are present.

If the graft surgery you emailed the link to is available, the teaching hospitals are the most likely places to be doing it. There are several articles on using grafts in dogs, mostly written as research projects to evaluate the use of grafts or graft protective medications in humans. This rarely benefits clinical patients since there is no support for the continuance of these procedures after the research needs are met, in many cases. The schools are usually happy to answer questions about whether or not they offer particular procedures and will often provide information on other places that are performing procedures that they do not do. It would be worth asking your vet to call Tufts and ask about available therapy.

I wish that I could help more with this situation. I hope that you are seeing some progress with the therapy undertaken so far.

Mike Richards, DVM 2/22/2001

Multi problems with heart murmur

Questions: Thanks for such a great service! I have a Schnoodle, approximately 11 years old or so. We've had her for just under a year, having gotten her from a rescue organization. She's very overweight, and at first, the rescue people suspected Cushing's. She was tested, and it came out that she had thyroid problems, so we give her two Soloxine pills daily. She's eating low cal dog food. Her weight hasn't really gone down significantly--a few pounds. (She's currently 18.6 lbs, down from about 21) Her fur is very thin, especially over her rump. A few days ago, she had an episode of staggering. My husband thought her paws were asleep, but I took her to the vet anyway. He discovered a heart murmur, about grade 4, he said. She also has a cough, which I understand is indicative of heart problems. Anyway, the vet didn't seem too concerned. He said he could send me off to get a full cardiovascular workup, but that would cost about $600, and so just watch her. He didn't offer any medications or other tests. I'm now very confused. Does she have Cushing's, a thyroid problem, heart problems, what? What tests should I ask about? I guess I should stress that this little dog is not just a pet, but a member of my family, and as such, is worth the money to keep her healthy as long as possible. I guess my question is just what questions to ask the vet. Thank you so much..

Answer: Stephanie- I think that it would be worthwhile to consider testing for hyperadrenocorticism even though hypothyroidism has been diagnosed already. It is not too unusual for dogs to have more than one hormonal disease. It is also possible for hyperadrenocorticism to lower the T4 levels. If a total T4 was the only test used to diagnose the hypothyroidism it is possible that this test result was influenced by the presence of another disorder such as Cushing's disease.

I also think that it would be a good idea to consider using some medications in a dog with a heart murmur and a cough. I tend not to treat dogs with heart murmurs immediately, preferring to wait until they develop clinical signs of heart disease. These signs include weight loss, lethargy, decreased exercise tolerance, coughing and fainting (syncope). Once signs develop, I do think it is a good idea to treat for heart disease. I do not think that all patients need a full cardiac work-up. Often, X-rays of the chest to rule out other causes of coughing is all that is necessary to justify the use of medications for heart disease when a murmur and clinical symptoms are present. I think it is best to consider having a cardiologist examine patients and run appropriate lab tests, such as cardiac ultrasound exam, but I don't consider it to be absolutely necessary for all patients. I like enalapril (Enacard, Vasotec Rx) when clinical signs are not bothering the patient too much but will use spironolactone and furosemide (Lasix Rx), in addition to enalapril, if there are signs that justify this use. Most of the time it is possible to relieve the coughing and to help patients feel better.

If you wish to have the best possible work up for your schnoodle and you are not concerned about the cost, you should let your vet know this. If you want to do the best possible job that can be done within a set amount of money, like $400 or $600, then you should let your vet know that, too. It sounds like your dog may benefit from hormonal testing or from a cardiac examination (or treatment for signs present) and you should be the one who determines if the cost is worth it to you.

Good luck with this.

Mike Richards, DVM 12/16/2000

Multi disorders with weight loss - continued

Question: Dr. Richards:

I'm a little confused so please forgive me if I seem thick headed this is a whole new world for me and I'm struggling to understand. Max has hyperthyroidism, diabetes and Addison's. As far as I know he never had Cushing's and was never treated for it. He was tested for Cushing's in June and that is when we discovered that he had Addison's. Prior to January 2000 he didn't take anything. In January he started with the Soloxine, in March we added insulin and in July we added Florinef.

Also, you mentioned in your response that the dosage of thyroxine was high. Is Soloxine the commercial name for thyroxine? He weighs about 85 pounds and is getting 2mg of Soloxine / day. Is that on the high side?

Thanks for all of your time I really appreciate it.

Dana Answer: Dana-

In this case, I think it is me who was confused. That happens sometimes when I try to answer too many questions in one night.

There are three current problems based on your notes. 1) hypothyroidism 2) diabetes mellitus 3) hypoadrenocorticism (Addison's disease). There is a condition referred to as autoimmune polyglandular syndrome, in which there are immune system problems which cause all three of these diseases to occur simultaneously, or some combination of them to occur. As far as I know, there is no treatment for the immune system influence on these conditions so they are all treated as if they occurred independently and coincidentally.

The usual starting dosage for thyroxine is 0.02mg/kg of thyroxine (Soloxine Rx) every 12 hours. For an 85 pound dog this would be about 0.8mg every 12 hours. This is usually administered until it is clear that a clinical response to the hormone supplementation has occurred or for a month or two. After this initial period, most dogs require less than 1 mg of thyroxine (Soloxine Rx) per day to maintain adequate levels of thyroxine in their blood stream and it is usually possible to give thyroxine once a day. The most accurate way to determine the necessary dosage for this medication is to do blood testing for thyroxine levels. Dogs are pretty resistant to adverse effects from giving too much thyroxine but it is still a good idea to try to give only the necessary dosage.

Addison's disease is usually treated with either fludrocortisone acetate (Florinef Rx) or DOCP or desoxycorticosterone pivalate ( Percorten-V Rx) when there appears to be suppression of cortisol levels and when there is no response to ACTH stimulation or very poor response. In some dogs, the cortisol levels are low but there is some response to ACTH stimulation and changes in sodium and potassium levels don't occur. These dogs usually only require supplementation with glucocorticoids (prednisone, for example). I think that Michigan State University runs a test for naturally occurring ACTH levels in dogs, to help differentiate between dogs that need mineralocorticoid (fludrocortisone, DOCP). If the ACTH level is high, then it is more likely that the dog has Addison's disease that will require Florinef or Percorten and if the ACTH levels are low, then glucocorticoid administration may be all that is necessary.

Most of the vets that I know monitor the electrolyte (sodium and potassium) levels, BUN and creatinine to determine if treatment for Addison's disease is working, which is what we do as well. So I don't have much experience using cortisol levels as a monitoring technique. Your vet may have good reason to monitor these, though, since it was a good call to pick up on the Addison's in addition to the other disorders.

I think I'd still be worried about the control of the diabetes as the major potential cause of weight loss but having all three of these conditions does make the whole situation very confusing. I don't envy you or your vet, since balancing the treatment needs of two hormonal diseases against each other is hard and three is very hard.

I'm sorry that I caused you some confusion with the initial reply. I'm glad you responded back and pointed out the error. Please feel free to ask for clarification or for additional information at any time.

Mike Richards, DVM 12/12/2000

Weight loss with Hypothyroidism, Diabetes and Addison's

Question: I'm hoping you may have run into this situation before and can give me some advice. My dog Max will be 10 in December. He's a mix but has always been a big dog. At his prime he weighed 110lbs and was not fat but very fit. I say this because I know that big dogs usually have shorter life spans and I realize Max is getting toward the end of his. He's had a terrible lick spot on his foot all of his life. We went to several different vets and tried many treatments with no success. Last fall/winter it got very bad and required several trips to the emergency vet clinic. Through the clinic he saw a vet who specializes in dermatology and we discovered he suffered from hypothyroidism. He has been taking 2 .5mg tablets of Soloxine twice a day since he was diagnosed and it has gotten his licking under control. While we were going through all this we noticed that he was loosing a lot of weight, drinking a lot of water and going to the bathroom all the time. In March he was diagnosed with diabetes. He regulated fairly quickly and bounced back but in June we noticed the dramatic weight loss again and took him back to the vet. He was diagnosed with Addison's disease and has been on Florinef since. He has been taking 0.1mg tablets - 1.5 tablets twice a day alternating with 1.5 tablets once a day since he was diagnosed. Again he bounced back but in August was accidentally given Humulin N instead of Humulin U. As soon as this was discovered he was immediately switched back and had put on a few pounds. Several weeks ago we went back to our vet for a regular blood check. His blood glucose was great - 83.5, but his cortisol level was 1.3. Here's our problem. We've increased the Florinef to 1.5 tablets twice a day every day when we got the results. He seemed to loose more weight and continued to be very thirsty. My husband was concerned about the weight loss and put him back on his old Florinef schedule. I spoke with our vet, who has been great but admits he's not quite sure what to do since he has three major problems, and we agreed to go back to the increased Florinef schedule, feed him twice a day and back off on the insulin. We were giving him 58 units we now give him 54 units. He's not on a special diet since we are afraid he wouldn't eat it and he can't afford a weight loss. Is there any advice you have? Do you know if the weight loss could be a short term side effect of the increased Florinef? Any help you could give would be great. Max has been a great dog and deserves the best.

Thanks, Dana

Answer: Dana-

This is a confusing set of problems to be dealing with, since there are many possible interactions.

I am assuming that the treatment for hyperadrenocorticism (Cushing's disease) led to the permanent destruction of the adrenal cortex, leading to the diagnosis of hypoadrenocorticism (Addison's disease). This can be a transient effect of treatment for Cushing's disease, or a permanent effect, depending on whether the adrenal gland was simply suppressed too severely (the goal of treatment is to suppress the adrenal glands, but not enough to make them stop working entirely). It would be necessary to monitor ACTH response tests for at least a few months to be sure that the effect was permanent. If not, you may be in a situation in which the Cushing's disease has returned but is not being accounted for. I am assuming that this is not the case but it is worth thinking about if no further testing has been done.

Weight loss is a symptom of unregulated diabetes and of unregulated hypoadrenocorticism. So my first guess would be that one or the other of these diseases is not being adequately controlled. It is more likely that the diabetes is not controlled well but you still have to consider both possibilities because hypoadrenocorticism is more likely to be fatal quickly, so checking to see if there is adequate control of this condition is worthwhile. Monitoring the serum potassium and sodium levels and the blood urea nitrogen (BUN) is usually enough to indicate if the Addison's disease is under control but in the situation in which Cushing's disease appeared first, it would be worth considering ACTH response testing, as well. For the diabetes, blood glucose curves are the most accurate test that we have at the present time for regulating the blood sugar level closely. It would be a good idea to consider this testing if it has not been done recently, since blood sugar samples taken only once a day may give the false impression that insulin is well regulated when it is not.

Lastly, the dosage of thyroxine is higher than the dosage that many veterinary endocrinologists think is necessary at the present time. Most dogs do not require more than 1mg per pound of body weight per day of this medication. Overdosages of thyroxine could lead to weight loss and increased drinking and urinating, just like the other hormonal diseases. I think that dermatologists and endocrinologists probably disagree about the upper limits of thyroxine supplementation but this is something to consider, anyway.

Since there are so many possible influencing factors, it seems like it would be best to consider them all, and to test for them in an efficient manner. Blood glucose curves involve drawing blood at 2 to 4 hour intervals for 12 to 24 hours and then evaluating a graph drawn from the blood sugar levels. This allows a more critical evaluation of the blood sugar levels over the course of the day. While drawing one of these samples it would be easy to draw blood to check the sodium, potassium and BUN values and also to get a sample about 8 to 10 hours after administration of the morning dose of thyroxin, to check serum levels of this medication. Then, depending on where all the other testing has led, it would be worth considering a recheck of the ACTH response test to be sure that the Cushing's disease is not recurring.

Mike Richards, DVM 12/4/2000

Problems with Yorkie puppy

Question: I am a current subscriber and have truly been enjoying your service.

I have a 6-month old female Yorkshire Terrier puppy that currently weighs just under 4 lbs. She is a typical puppy in most respects, but has had these "strange" occurances that our veterinarian can't seem to figure out. She says she has never seen similar symptoms in another animal. Although we are continuing with some "general" bloodwork testing, we keep ending up with no explanation. I thought maybe you have had some experience with this problem and/or could help me to request adequate tests to attempt a diagnosis.

One day when she was 3 months old, she had been playing and eating as usual, when we noticed that all of a sudden she became disoriented and began turning in circles and darting her eyes and head all over (not really looking or listening to anything in particular) and she didn't seem to know that we were talking to her and she would not make eye contact with us. She did not want to be held and when we called her name, she would go and hide under the table as if she was panicking. She paced the floor and seemed completely "out of it" and she would not eat or drink anything. We rushed her to our local veterinarian who seemed to believe she had an "inner ear infection" and gave her an anti-inflammatory injection and some antibiotics to give her by mouth. She was also running a 104 degree fever. This all began around 11:00am. At around 5:00pm, she was no better -- and actually seemed worse -- so we took her to the local "emergency" veterinarian's office. They did not seem to believe it was an inner ear infection but they couldn't explain what it was. They gave her valium intravenously and took some blood. He told us to keep her in a quiet confined area so that she could begin to relax. At about midnight that evening, she "snapped" out of it and seemed completely normal again -- biting on us and kissing everyone. The next day, the emergency pet hospital called and said that the test results came back with the possibility of Addison's Disease and asked us to get our veterinarian to run additional tests. My veterinarian didn't feel further testing was necessary until she showed further signs of illness -- because she continued to feel it was an inner ear infection.

One evening this past week at about 5:00pm, the entire episode began again. She had the exact same symptoms. We took her to our vetinarian who took blood and sent us home with valium. Our vetinarian did not have an explanation but wanted to see what the blood tests results would show. That evening, the valium did not seem to have any affect on her and she "snapped out of it" at about 5:00am the next morning -- after crying and pacing the floor all night. The only difference between this and last time is that she would sit for a few seconds instead of pacing constantly.

The test results came back normal -- except that there appears to be a large number of white blood cells and she seems fine today. Our veterinarian said that she would run any test that we wanted but she didn't know where to go from here except to send us to an internal medicine specialist.

Have you ever seen or heard anything like this? Do you have any suggestions for me. I want to find out what is causing this. I can't handle seeing her go through these "fits" again.

Sincerely, Marva

Answer: Marva-

The first thing that came to mind when I read your note was a problem with circulation through the liver. Yorkshire terriers are prone to portosystemic shunts and to hepatic microvascular dysplasia. In both of these disorders the normal circulatory flow of blood through the liver is disturbed and the result is a decrease in liver function. Yorkie puppies may seem normal until they reach a size that it is hard for their body to cope with the deficient liver function and then clinical signs appear. The signs can be somewhat variable but periods of decreased mental function, disorientation, difficulty walking and seizures are all reported to occur in some dogs.

The best initial test to start to rule in or out the possibility of an hepatic circulatory disorder is bile acid response testing. This is an easy test to run and any small animal veterinary hospital should be able to handle the testing. If the bile acid response test is suggestive of a liver disorder these are the most common ones. Portosystemic shunts usually cause severe differences in pre and post-prandial bile acid levels. Microvascular dysplasia usually causes moderate changes in pre and post-prandial bile acid levels. Portosystemic shunts often require surgical correction but microvascular dysplasia can usually be managed by diet and medication.

Another possible problem is hydrocephalus, which is increased fluid pressure in the brain. This usually shows up as depression, seizuring, difficulty walking or related problems at an earlier age than your Yorkie showed signs but sometimes problems don't surface until later in life. This problem occurs in Yorkies occasionally. Most vets are pretty good at recognizing the possibility that this disorder is present but sometimes the typical domed head appearance isn't present, making it harder to recognize the problem.

Hypoglycemia is sometimes a problem in small breed dogs, too. This is also more common in younger puppies but could potentially be a problem. Usually this will show up in lab work if it is checked for at the time the problems are occurring, though.

Addison's disease can cause signs similar to what you are describing, too. It will often cause cause a low heart rate, inappetance and sometimes other GI signs, especially vomiting. There are a lot of other possible clinical signs. In lab work, a higher than normal potassium level coupled with a low normal to lower than normal sodium level, producing a sodium to potassium ratio of less than 27:1 is considered to be suggestive of hypoadrenocorticism (Addison's disease). The best test for confirming this condition is the ACTH response test. This is a life threatening illness and if there is reason to suspect it based on the original labwork it would be best to try to confirm that it is present or to rule it out by running the ACTH response test. Yorkies are not particularly prone to this disorder.

I think that the order of likely occurrence of these conditions is hepatic microvascular dysplasia (HMD), followed at a distance by portosystemic shunt, then hypoglycemia and hypoadrenocorticism. Unfortunately, the importance of these conditions is almost exactly the reverse of the normal likelihood of occurrence, so it is hard to tell you to start with testing for HMD and then go back and test for Addison's. If the cost of testing isn't a major problem, I think I'd be inclined to test for both conditions at the same time if I really thought that Addison's was likely based on the initial labwork and clinical signs, especially if a low heartrate is also present.

There are a lot of other potential problems. Encephalopathies (brain disorders) can occur for a number of reasons, encephalitis (brain infection/inflammation) is a slight possibility and we have seen signs reasonably close to what you report in a Yorkie with a malformation of the atlanto-axial joint (the joint between the first and second vertebrae).

If your vet wishes to refer your Yorkie to a specialist at this point, there is no reason to fight that impulse. The specialist can sort through these problems quickly. If it is hard to arrange a visit to a specialist it would be easy to do bile acid response testing and possibly ACTH response testing while you wait for the visit.

Good luck with this.

Mike Richards, DVM 1/26/2000

Multi-symptom problem - Lab/shep mix

Q: My seven year old mixed yellow lab and terrier/Shepherd male dog recently developed rather sudden onset of extreme lameness in all legs, exteme lethargy and occasional labored breathing. My vet suspects Lyme disease although his titer was negative. Two days after onset, at the site of an old skin tear over his rib cage, he developed a large lump, approximately half the size of a football. It took about three days to grow to this size and is hot to the touch. The vet first ignored it, then upon my insistence, tried to draw fluid from it, assuming it was hematoma. He was unable to get any fluid. The examined cells appear to be normal. The lump appears to have stopped growing and is now very hard, although it was never really soft - it is just harder now. He has been on doxycycline for eight days with no improvement (2 1/2 tablets in the morning, not sure how many mgs.) I am very worried. Sunny has been a very vigorous, active dog all his life. Now he can barely walk, only rising to urinate and defecate with great difficulty. He is very listless, appetite almost gone and is getting very irritable and snappish although he does not appear to be in much pain. He is a very stoic dog, though, and may be in pain.

A: K

It is always tempting to lump all the signs together and assume that one problem is causing them (because this thinking works well most of the time) but I think it would be a good idea to keep in mind that there may be two problems occurring at the same time, one causing the lump and one causing the other problems.

The major reason I mention that is because I'd be really tempted to surgically explore a lump that came up that fast that I could not aspirate anything from. And because I think there may be a need for immunosuppressive medications for the sudden onset lameness and if the lump is hiding an abscess, it would be good to know that before using an immunosuppressive agent such as prednisone or azathioprine (Imuran Rx). Exploring the lump may reveal the underlying cause for the development of lameness (such as as septic arthritis) but it may not help much in determining the best course of action in treating the lameness.

In acute onset lameness of more than one leg in an middle-aged dog I tend to think about rickettsial diseases (Rocky Mountain Spotted Fever, Lyme, ehrlichiosis), immune mediate polyarthritis, bilateral cruciate ligament ruptures, spinal disease, hip and elbow dysplasia aggravated by other conditions, drug reactions (sulfas, in particular), cancer, and fungal or bacterial infections that are invading the bones or joints.

In older Labs I try not to overlook immune mediated hemolytic anemia, hemangiosarcoma and lymphoma when there are sudden odd clinical signs that affect more than one area of the body. Shepherds tend to have similar tendencies although less lymphoma and more immune mediated diseases like lupus.

It is always hard to figure out what the best approach to a multi-symptom problem is, but I'd lean towards looking into the lump carefully, including removing it if necessary to determine what it is and to test for other problems simultaneously. Your vet will have to help you decide which conditions seem most appropriate to test for first, based on the clinical signs and lab values you have so far.

If anemia has been ruled out, that helps. The rickettsial diseases can often be tested for in one panel, from serum. In your area, Lyme disease does seem like it has to be high on the list of differentials. Determining whether the problem is primarily in the rear legs, primarily the front legs, mixed between one front and one rear leg or occurring in all four legs can help in thinking about the potential for injury to the cruciate ligaments, spinal discs, etc. Immune mediated joint disease diagnosis may require aspirating joint fluid (especially important to consider if the joints are swollen) and the immune mediated diseases may require specialized blood testing. When aspiration fails to reveal what a lump might be, surgical biopsy is the next step, unless it is going away due to treatment efforts. In areas in which fungal infections are common (Ohio River valley, the Southwest) this is another thing to consider. Your vet should know if you are in an area in which this occurs but I can't remember the NorthEast being too suspect.

Due to the complexity of sorting through these problems we tend to refer patients to a veterinary teaching hospital when we really think the patient might die while we try to make a diagnosis. They are just equipped to get through the whole process faster. This might be an option for Sunny's situation, if it is possible for your vet to refer you to a vet school or large referral center in your area.

Pain relief can be very helpful and should be considered if you are not already providing something to relieve the pain and inflammation.

Hope this helps some.

Mike Richards, DVM 9/8/99


Michael Richards, D.V.M. co-owns a small animal general veterinary practice in rural tidewater Virginia. Dr. Richards graduated from Iowa State University's College of Veterinary Medicine in 1979, and has been in private practice ever since. Dr. Richards has been the director of the PetCare Forum...