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Author Topic: ADDISON'S DISEASE  (Read 8095 times)

Jo CIMDA

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ADDISON'S DISEASE
« on: July 29, 2014, 10:20:49 PM »

Diagnosis: Kidney Disease
Or is it?

The difference between the clinical signs and blood analysis of kidney disease (causing renal failure) and Addison’s disease is very subtle, that is unless you are aware of what you are looking for, and then the possibility of primary Addison’s disease can become so obvious it stares you in the face! 

Vets could be forgiven for not recognising the vague, non-specific clinical signs of Addison’s disease if the consequences of a misdiagnosis were not so dire.  It will most certainly result in the premature and unnecessary death of your dog.

In just three months, two Addisonian cases I have been involved in were originally misdiagnosed as definite cases of kidney disease. The dogs were put on a KD diet (a special veterinary diet for dogs with kidney disease) and no improvement was seen. Both dogs were deteriorating, and when Addison’s disease was mentioned to the vets’ they dismissed it. After the owners were made aware of the clinical signs and typical blood results of dogs with Addison’s disease, it seemed very possible to them that their vets had misdiagnosed their dog’s condition. The information gave them enough courage to challenge their vet’s diagnosis and in both cases this resulted in a confirmed diagnosis of Addison’s disease, which undoubtedly saved the dogs’ lives.

These two cases were almost identical, so how many other dogs are being misdiagnosed and dying needlessly?  Many years ago when I had to take one of my dogs to the Royal Veterinary College, the vet looking after him told me that in the previous three days, four dogs had been admitted to the hospital with Addison’s disease.  He said if veterinary surgeons only looked at their text books it would not be necessary for these dogs to be referred to the vet college!  No one is saying that Addison’s is an easy diagnosis to make, as it shares so many similarities with kidney disease (and other diseases), but there are tell-tale signs that not only should the vet be aware of but also the owners, and if these signs are apparent it should be enough reason to suspect Addison’s disease.

Although Addison’s disease has been diagnosed in a dog as old as 14, it is more likely for an aged dog to have degenerative kidney disease than Addison’s disease. This article is more relevant to dogs of young to middle age, as this is when Addison’s disease is more likely to occur, especially in a breed known to be genetically predisposed to this disease. 

Much has been written about Addison’s in the past.  This article is intended to give a brief outline of the disease, concentrate mainly on the common factors, and more importantly the subtle differences between kidney disease and Addison’s disease, and how the tell-tale signs can be identified from the blood results. You don’t have to be a vet or scientifically minded, just look at the overall picture and be brave enough to challenge your vet’s diagnosis and ask for an ACTH stimulation test, if for no other reason than to rule it out and give you peace of mind.

Primary Addison’s disease (hypoadrenocorticism) is the result of an autoimmune destruction of the adrenal glands.  The adrenal glands produce several hormones; the most important of these are aldosterone (a mineralocorticoid) and cortisol (a glucocorticoid).  Insufficient production of these hormones alters the electrolyte balance in the body, in particular the sodium and potassium levels, and can produce clinical signs such as:

Lethargy, depression, nervousness, weight loss, anorexia (no appetite), vomiting, weakness (particularly of the back legs), shaking or muscle tremors, limping, diarrhoea (with or without traces of blood), abdominal pain, dehydration, excessive thirst and urination, weak pulse, slow heart rate and abnormal heart rhythm, anaemia (pale gums) and collapse. One important difference between acute/chronic renal failure and Addison’s disease is, the heart rate in renal failure is more likely to be fast (Tachycardia) and in Addison’s disease it is more likely to be slow (Bradycardia).  Signs of the disease are most apparent when the dog is physiologically or psychologically stressed.

Addison’s disease is progressive and it can take many months before clinical signs are seen. Sadly, in some cases - if subtle changes are missed - the first sign can be death.  Clinical signs are often vague to start with and can seem insignificant, but this is a common observation of the disease. Outward signs wax and wane and respond to fluid therapy or can worsen with stress. As the autoimmune destruction continues the adrenal glands will reduce in size until they are unable to produce enough adrenal hormones to sustain the dog. At this point the clinical signs, and abnormalities in the blood, are increasing and the dog is at risk of collapse, and subsequent death.  It then becomes a serious veterinary emergency, and it is very desirable to achieve a diagnosis before this occurs.  Unfortunately, it can become a fight against time to get the vet to even consider that the dog may have Addison’s disease. A common remark is ‘Oh, it won’t be Addison’s, we never see it’.  Never see it, or never diagnose it?

If your dog is visiting the vet regularly because of continuing symptoms, ask for a Complete Blood Count (CBC) and a full biochemistry blood test to be done, and don’t forget to ask for a printout of the results for your own records. The printout will show you a list of different chemical values, some of which are mentioned below.  The most important ones to look at in a case of Addison’s disease are the sodium and potassium levels.  However, not all cases of Primary Addison’s disease will have all the clinical signs and blood abnormalities, and this has to be borne in mind.  Also, there is a less common condition called Atypical Addison’s disease, in which the dog is deficient in cortisol only. Cortisol enables the body to cope with stress, and clinical signs relating to a deficiency may include: depression, nervousness, anorexia, weak pulse and collapse, particularly in stressful situations.  The adrenal mineralocorticoid hormone regulates the conservation of sodium and excretion of potassium from the body.  In atypical Addison’s this is less severely affected therefore the sodium and potassium levels may be within normal range.

Greater than 90% of Primary Addisonian cases will have high potassium and low sodium values, with a ratio of less than 27.  Prior to diagnosis, Addisonian dogs often show a ratio of less than 23. However, the ratio alone is only suggestive, and not diagnostic, of Addison’s disease. Individual electrolyte concentrations can be more reliable. As the disease progresses, the ratio will drop even further and the dog may collapse and become critically ill. ¹

Routine Laboratory Abnormalities  -  Haematology & Biochemistry
INCREASED: 
High Potassium (K)
High Creatinine,
High Urea, (BUN – blood urea nitrogen; or SUN - serum urea nitrogen)
High Urea/creatinine ratio (Azotaemia)
Increased Eosinophils
Increased Lymphocytes
High Bilirubin -  in some patients
High Calcium (mild to moderate) – in some patients
ALT- ALP - AST (Mild to moderate increase of liver enzymes) – in some patients
DECREASED:
Low Sodium  (Na)
Low Sodium/potassium ratio (K:Na ratio -  less than 27) Addisonian dogs often have a ratio of <23.
Low Chloride  (80% of Addisonian dogs will have low chloride values)
Low Glucose – in some patients
Low Albumin (moderate to severe) – in some patients
Total white blood cell count (WBC) – in some patients
Red blood cell count (RBC or HCT)

Another possible difference between kidney disease and Addison’s may be seen in the white blood cells (eg., neutrophils, eosinophils, lymphocytes). When a dog is poorly he becomes stressed and this is reflected in the white cells. The neutrophil numbers would be expected to be high/normal or increased, and the eosinophils and lymphocytes would be decreased or low/normal numbers. This is called ‘stress leucogram’ and is seen in both chronic and acute renal failure, but not in Addison’s disease. A dog with Addison’s disease may show a much lower white cell reading than would be expected in such a poorly dog.  In fact there may even be reverse of what would normally be expected, eg., low/normal values of neutrophils and a higher value of lymphocytes and eosinophills (called a ‘reverse stress leucogram’). ¹ ²
The terms used above might sound a bit too scientific but all of these values are clearly written on the laboratory report with the reference range, so it is not difficult to see if something is high or low and you may be able to build up a picture that may lead to a possible diagnosis. One point to remember, as Addison’s is a progressive disease, remarkable values may not be present in the earlier stages.  If the problems are ongoing regularly recheck the subsequent blood results for any of the above abnormalities.
Points to consider:
Is your dog young / middle aged?
Over a period of time, has your dog experienced several of the symptoms listed above and has he/she responded well to fluid therapy?
Has your young to middle aged dog been diagnosed with kidney disease?  Is he/she improving on the treatment/diet provided by your vet? If the answer is no, then consider Addison’s disease.
Do you have a dog whose breed is known to be genetically predisposed to Addison’s disease?
Do you know of any relatives of your dog who may have been diagnosed with Addison’s disease or kidney failure at a young age, or other autoimmune disease? Speak to your dog’s breeder; he/she may be able to give you valuable information.
Have a Full Serum Biochemistry panel and a Complete Blood Count test done and ask your vet for a copy of the results for your own records.  Study the results yourself and check for the abnormalities listed above. If symptoms persist, have a further blood test done to see if there are any changes, but don’t leave it too long in between (a week or less) as deterioration seems to quicken in the last stages.  Keep each laboratory report for comparison. Blood testing is never a waste of money (in the long term it can save you money), and it provides a ‘bench mark’ on which to base further tests).
What to do if you if your dog continues to deteriorate and you suspect that he/she may have Addison’s disease.
If your dog is extremely poorly, eg. very lethargic, call your vet straight away, regardless of the time, or if it is a weekend or Bank holiday. Tell your vet of your concerns and suspicions. Relay clinical signs and draw attention to any significant blood results. It is surprising how many vets miss the significant sodium/potassium clue.
If the breed is genetically predisposed to Addison’s, stress this to your vet.
The vet should respond by asking you to take your dog to the surgery immediately.  If your vet shares your suspicions he may carry out an ACTH stimulation blood test. (Unfortunately this is not possible over a weekend).  If your vet does not respond to your concerns then start making telephone calls until you find one who does. Don’t worry about offending your existing vet; your dog may be in extreme and immediate danger.
If your dog is too poorly for an ACTH stim test and has typical electrolyte imbalance usually seen in primary Addison’s disease, then your vet will need to give life saving treatment, eg., saline (sodium) intravenous fluids to re-hydrate, and bring down the dangerously high potassium levels and raise the sodium levels in the blood, and an intravenous injection of dexamethasone to enable your dog to cope with the stress.  ²
NOTE:  Dexamethasone is a glucocorticoid but unlike prednisolone it does not interfere with the ACTH stim test. 
Giving intravenous fluids and dexamethasone will hopefully support your dog until the result of the ACTH stim test is known.  Do not leave your dog without supportive treatment at this critical time.  It wouldn’t be the first time that a dog has died waiting for the results of the ACTH stim test to come through.
If the result is positive, your dog will be prescribed a mineralocorticoid hormone called Florine-f.  The initial dose is usually on the low side, and is gradually increased until the sodium and potassium levels are within normal range and clinical signs have resolved. The treatment must be given every day for life (usually the dose is split and given twice a day).  For the first few weeks or so your dog will also be on prednisolone (a glucocorticoid). Once stabilised, there is usually enough glucocorticoid in Florine-f to control everyday stress levels, so the prednisolone can be withdrawn. At times of added stress, however, (caused by fireworks or even going to the groomers etc.,) the owner must give additional prednisolone to enable the dog to cope with the trauma.  These are replacement doses and are vital to an Addisonian dog’s survival and should not be confused with higher treatment doses of steroids used to treat inflammatory conditions.  The body is designed to produce these hormones on a supply and demand basis.  An Addisonian dog no longer has the ability to do this and they rely on the owner to anticipate stressful situations and administer the appropriate medication. It is not a difficult regime to follow once the dog is stabilised and you are familiar with the condition.
Initially, blood tests to check electrolytes should be every 5-7 days and as clinical signs improve and blood results return to within normal limits the tests can become less frequent.  Electrolyte blood tests should still be carried out every 6 months when the dog is stable.   
In the United States dogs with Addison’s disease are more often treated with intramuscular or subcutaneous injections of desoxycorticosterone pivalate (DOCP – trade name Percorten-V.)  Dogs seem to do better with these injections than with Florine-f.  The dosage must be balanced by effect, both in the amount of the drug given and the interval between injections.  This can range from every 20 to 35 days, but usually is every 26-28th day.  After the initial injection sodium and potassium levels will be evaluated at 12 and 25 days to determine the size and timing of the next injection.  DOCP has purely mineralocorticoid activity, and so it is necessary to give a small dose of prednisolone – usually 2.5mg to 5.0mg every 24 or 48 hours. 
Many dogs with Addison’s disease also are hypothyroid, and treating their thyroid problem tends to make treating the Addison’s easier.  Usually the dog will require less Florine-f or DOCP, and will handle stress better too. 
The resolution of both clinical signs and blood results must be taken into consideration when evaluating the dog’s progress and should not be used in isolation. Remember in Addison’s disease especially, clinical signs usually reflect blood results and vice versa, but one may lag behind the other. If your dog is receiving an appropriate dose of Florine-f (this can vary from dog to dog) and his/her clinical signs or blood results do not stabilise after a few months, a full biochemistry blood test to check kidney/liver function etc., may be useful, or ask your vet for a referral to an endocrinologist, just in case there is an unidentified, underlying problem. 
If the ACTH stim test does not confirm Addison’s disease, it may have to be repeated at a later date if clinical signs and blood abnormalities persist.  The result of the ACTH stim test reflects the ‘current’ adrenal function status and may not show a ‘flat line response’- which is diagnostic of Addison‘s disease - until much later in the disease process. 
The good news is that the prognosis for Addison’s disease is usually excellent. Dogs can go on to live a happy, normal life on daily medication for many years, living well into old age, 15 or 16 years. It is certainly a much better prognosis than kidney disease.

Jo Tucker
References:
1. BSAVA Manual of Canine & Feline Clinical Pathology
2. BSAVA Manual of Small Animal Endocrinology
Additional information from Linda Aronson DVM
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