Will steroid-induced Addison's symptoms disappear without treatment?

Started by Alicat, November 25, 2013, 05:47:35 PM

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Alicat

Dear Jo

Your Canine Addison's article is an excellent reference source.  However, I simply cannot find an answer to my query ... Perhaps, based on your biochemical knowledge, you can shed some light?

My dog's medical problems are long and complicated, but I will try to keep it brief (!):  He is an 11 year old  Retriever, generally very fit, healthy, muscular and happy.  3 years ago he contracted Ehrlichiosis.  Many complications and lengthy period before correct diagnosis.  He survived near-fatal symptoms during acute(2010) and chronic (2011) phases.  Treated with antibiotics and steroids (Preds) over several weeks, platelet count went from 4 up to several hundred (2012).  He did not tolerate steroid side effects at all well, but gradually appeared fully recovered once weaned off.

This year, after many stressful life changes and gradual symptoms, his ehrlichiosis had seemingly been re-triggered and platelet count dropped to 9.  Almost 5 months treatment of antibiotics and two courses of Prednisolone has seen platelet count rise to 77+.  But side effects of preds cumulative and almost intolerable and although weaned off slowly, he initially showed signs of having been pushed into Cushing's, plus an apparent nasty urine infection and loss of blood (more antibiotics appeared to clear up the problem).  He has experienced severe muscle atrophy and weakness and, since finishing the steroids completely, has vomited digested blood, tremors/trembling, diarrhea, collapse and general anxiety. He is currently receiving treatment for gastro-ulceration in case this is the cause, but it seems likely that the steroids have swung him towards Addison's.

So, finally, my query is - if this is a case of steroid-induced Addison's, is it possible that the problem will resolve itself?  After his several months on steroids, is it possible that his various 'chemicals' will re-balance themselves once they've had a chance?  Because all information available suggests that steroids are the only standard treatment regardless of cause of Addison's.  Or is it a known fact that without administering glucocorticoid treatment, the condition will only deteriorate, howsoever caused?  I am desperate to find out because he cannot possibly tolerate any more steroidal treatment and I will not subject him to that misery (or to a further battery of comprehensive diagnostic tests if steroid treatment is the only solution anyway), so I must think about making 'the big decision' before he suffers further deterioration.  But I don't want to have him put to sleep only to learn that, given a few weeks, his symptoms might naturally have eased.

I would be grateful for any information you can give me and thank you sincerely for your time.


Jo CIMDA

Quote from: Alicat on November 25, 2013, 05:47:35 PM
Dear Jo

My dog's medical problems are long and complicated, but I will try to keep it brief (!):  He is an 11 year old  Retriever, generally very fit, healthy, muscular and happy.  3 years ago he contracted Ehrlichiosis.  Many complications and lengthy period before correct diagnosis.  He survived near-fatal symptoms during acute(2010) and chronic (2011) phases.  Treated with antibiotics and steroids (Preds) over several weeks, platelet count went from 4 up to several hundred (2012).  He did not tolerate steroid side effects at all well, but gradually appeared fully recovered once weaned off.

Hello,  Yes your boy's  problems are complicated and I will try to answer your questions as best as I can  but it is difficult without more information so please excuse the many questions.  Can you give me an idea of the treatment regime your boy was on eg., initial dose of preds, and the duration/reduction regime and  his weight. 

This year, after many stressful life changes and gradual symptoms, his Ehrlichiosis had seemingly been re-triggered and platelet count dropped to 9. 
Did he test positive to ehrlichiosis this time or was it assumed?  If a dog relapses it may not have been the same trigger as the first time around.

Almost 5 months treatment of antibiotics and two courses of Prednisolone has seen platelet count rise to 77+.  But side effects of preds cumulative and almost intolerable and although weaned off slowly, he initially showed signs of having been pushed into Cushing's, plus an apparent nasty urine infection and loss of blood (more antibiotics appeared to clear up the problem).  He has experienced severe muscle atrophy and weakness and, since finishing the steroids completely, has vomited digested blood, tremors/trembling, diarrhea, collapse and general anxiety. He is currently receiving treatment for gastro-ulceration in case this is the cause, but it seems likely that the steroids have swung him towards Addison's.

Again I would like to know the dose/duration/reduction etc.,  of the preds and I presume the vet didn't give a gastroprotectant and this is why he has the gastro problems.  This is an almost predictable outcome if a gastroprotectant isn't given.   Is his platelet count more than 77 now?
The only way steroids can swing a dog from Cushing's to Addisonian is if the steroids are withdrawn too quickly.  Steroids must be reduced gradually otherwise adrenal insufficiency will occur and the dog can go into an adrenal crisis. When a dog is on preds the part of the adrenal glad that produces cortisol shuts down, as there is no demand for cortisol because it is being artificially supplied  by the preds.  By weaning a dog off steroids slowly and then tapering to every other day dosing it allows the adrenal glands to 'wake up' and start to function normally again. If a dog has to be taken off preds quickly then at least a replacement dose of preds should be given (0.2-0.5mg/kg/day or every other day) to support the dog until his adrenal glands start to function fully again.


So, finally, my query is - if this is a case of steroid-induced Addison's, is it possible that the problem will resolve itself? 

If your boy is off of steroids then the vet can perform an ACTH test to see if he is able to produce cortisol and therefore truly Addisonian. If his current problems are due to insufficient cortisol then he can be supplemented with low dose of preds until such time that his adrenal glands can function properly again.  As far as I know steroid treatment does not destroy the adrenal glands but it does temporarily shut them down whilst the dog is being supplemented with corticosteroids.

After his several months on steroids, is it possible that his various 'chemicals' will re-balance themselves once they've had a chance?

YES

Because all information available suggests that steroids are the only standard treatment regardless of cause of Addison's.

Steroid treatment will cause Iatrogenic (drug induced) Cushing's but these effects usually reverse over time once the steroids are weaned to a low, every other day dose or gradually, totally withdrawn.   As previously stated Steroids will only produce iatrogenic Addison's if the steroids are withdrawn too quickly and if this happens the dog has to be supported by re-introducing preds at a replacement dose and gradually withdrawing supplementation.

Or is it a known fact that without administering glucocorticoid treatment, the condition will only deteriorate, howsoever caused?

The aim of immunosuppressive treatment is to achieve remission – and in a dog with IMTP this can realistically happen.  The best immunosuppressive drug that is very quick acting is prednisolone.  If a dog continues to relapse then another immunosuppressive drug can be introduced and this combination therapy usually works very well.  If a dog relapses after achieving remission then the dog has again, met a trigger but it may not be the same trigger.

I am desperate to find out because he cannot possibly tolerate any more steroidal treatment and I will not subject him to that misery (or to a further battery of comprehensive diagnostic tests if steroid treatment is the only solution anyway), so I must think about making 'the big decision' before he suffers further deterioration.  But I don't want to have him put to sleep only to learn that, given a few weeks, his symptoms might naturally have eased.

I can't agree with you more.  You have tried very hard with your boy and he does deserve to achieve remission and continue to have a good life  - and this is possible.  I am interested to know what drug regime he has been on because the dose and duration is crucial to the outcome.  Some dogs are more difficult to stabilise but sometimes it is the treatment that's not correct and no matter how many times you re-introduce immunosuppressive treatment, if the regimen is not correct then you will not achieve your aim.

Jo



Alicat

Dear Jo

Thank you so much for the time and trouble you have taken to reply.  I will try to answer your questions, but he (Oscar) has had so many meds, on, off, up, down, that I will really struggle to remember it all precisely, but I will do my best.

Initially, (after horrendous central nervous system/optic nerve pain/damage, collapse and fitting, once Ehrlichiosis finally diagnosed and platelet count was just 4 in Aug 2011) we were living in France (wonderful vets!).   O. used to hover around 30kg. He was put on high dose 80mg p/day Preds. and antibiotics.  After a few days he reacted so badly to steroids, but we persevered at (80mg) 2 tablets p/day for 2 weeks then blood test showed platelet count up around 280, so vet agreed to start reducing to help ease dreadful side-effects.  So, down to (40mg) 1 p/day for 5 days, 1/2 p/day 5 days, 1/2 every other day for 5 days.  Results - excellent.  Subsequent blood tests showed high platelet count stabilised.  Happy, healthy dog, just residual optic nerve damage in 1 eye.

Late 2012/early 2013 - amongst other things, we moved back to UK, moved house 3 times and, for O. many other stressful, but unavoidable events.  His behaviour became more and more anxious, fearful and, physically, reminiscent of pre-low platelet count (fatigue, excessive panting/barking, hair loss, skin irritation, etc.).  I explained his history and asked new UK vet for a platelet count. (He's not had 1st-hand experience of Ehrlichiosa Canis).  He also ordered a different blood check to apparently look for suggestion of Ehrlichiosis.  The manner of results formula did not give an exact figure, but reported platelet count was indeed low - 2/3rds lower than average, and whatever the other test was suggested Ehrlichiosis probably not dormant in bone marrow. Vet determined that previous Ehrlichiosis had so damaged O.'s immune system that due to recent month's of stress it simply couldn't cope and was attacking itself.  Therefore, no antibiotics prescribed, but Preds started (no gastroprotectant.) - here I start to get vague with dosage!  Anyway, much lower than previously, (25mg) 1 tablet daily for 10 days, then down to 1/2 daily x 5 days, then 1/2 every other day x 10 days (side effects were awful again, and I just cannot remember why...but) went up again to 1/2 daily x 5, then down again to 1/2 every other day for 10 days.  Before the end of the final 10 days, 2 more platelet tests had shown a further drop, to 36, then down to 9, so steroids not resolving problem.  (Meanwhile, O. deteriorating rapidly). 

Vet took advice, it was decided we must assume Ehrlichiosis indeed still present and re-triggered by stress (I refused marrow biopsy from hipbone. for O.'s sake).  On the basis of successful treatment in France, continued Preds but starting again right back up at 75mg (3 tablets daily) for 14 days, plus doxycycline, plus gastroprotectant (Antepsin).  Then down to (50mg) 2 tablets daily x5 days, then 1 daily x 5 days (O.'s side effects unbearable - for me and him!), then 1/2 daily for 10 days, then 1/2 every other day for 10 days (finished last week). 

Two platelet tests at the end of the 75mg p/day, and again 2 weeks later, showed rising platelet count to 56 and 77 respectively.  The 77 count (lowest estimate found, so probably higher and good clumping) was 14 days ago. Despite showing signs of having been pushed into Iatrogenic Cushing's 4 or 5 weeks ago, as weaning off continued symptoms improved enormously, helped by platelet rise (The most noticeable change was lack of anxiety - would this suggest cortisol production?).  During last 10 days of weaning off Preds and finishing 2 months of doxycycline, O. started urinating heavy blood and blood clots (thought to be waste matter from muscle wastage or urine infection, though no other signs of infection).  5 days of urine-infection specific antibiotics immediately post-doxycycline and by 4th day urine was clear.  O. was like a puppy (albeit weak) for a few days, shiny, happy, running, chilled out, vet delighted, me ecstatic (this was last Tuesday). After 2 days completely off steroids, he vomited blood, collapsed and started exhibiting the Addison's symptom's previously described.  (My vet was away, but over the phone suggested commencing the treatment for gastric ulcer; an assistant has since suggested the Addison's).

Sorry to go on and on - but it's never-ending!  Anyway, despite collapsing 10 times, O. has not now collapsed or vomited since Friday, but diarrhea/loose stools (yellow, mucousy, slightly bloody) and occasional tremors continue (6 disturbed nights so far to rush outside!).  He is clearly weak, thin (not sure of current weight but has probably lost at least 5 or 6 kg during Preds treatment), somewhat listless, though still keen to eat and drinking regularly but no longer excessively. 

So ... although he was weaned off the Preds in the proper way, it does seem possible that the up/down on/off dosages may have confused the adrenal glands.  But I swore I would say goodbye to him rather that put him through any more steroid treatment.  And therein lies my original query.  If it is Addison's is re-introducing Preds the only way? He just can't take it and I don't think I can either!

Exhausted, tearful, and grateful for any advice you can give.  Thank you so much.

Jo CIMDA

Hi

Immunosuppressive treatment dose for prednisolone is 1-2mg/kg/12hrs Plumb's Veterinary Drug Handbook.  The aim is to give the lowest dose to control the disease and this is usually initiated at 1mg/kg/12hrs.  A dog weighing 30kg would normally be started on 30mg of pred given twice a day.  Although 80mg a day is still within the immunosuppressive dose it was probably more than Oscar needed, especially as larger dogs do not cope as well as smaller ones when on very high doses of preds.   This is probably why the adverse effects were so drastic and unacceptable.

You will see by the reducing immunosuppressive drug protocol by Professor Michael J day,  copied below,  that the drug reducing protocol's Oscar has been on were very different.  This  really is the best  protocol I have known and any vet can confidently use it as a guide although, as always, the drug protocol is tailored to the individual depending on clinical signs and side effects of the drugs.  The duration of Oscar's  drug regimes were hastened, but because the dose went to every other day before withdrawing the preds it would not have caused iatrogenic Addison's disease.   

The clinical signs of Addison's disease are numerous and it is known as 'The Great Pretender' because it mimics so many other diseases.  Oscar may have collapsed due to blood loss or iron deficiency anaemia as a result of gastric ulcers. This seems to be the most obvious explanation.  If you are concerned that Oscar may have primary Addison's disease then your vet should do a full biochemical blood profile and a complete blood count.  This should indicate Addison's if his adrenal glands are struggling and if there are indicators then your vet should perform an ACTH test.  The  way both vets reduced the steroids, in my opinion,  would not have caused drug induced Addison's disease. 

If it is Addison's is re-introducing Preds the only way?   

I'm not sure I really understand this question.  If Oscar has a relapse of IMTP then steroids or other immunosuppressive drugs (including perhaps a one off injection of a  drug called Vincristine) is the only way to stop the immune destruction of the blood platelets and bring the disease into remission.  BUT the protocol is crucial to the outcome and I would suggest Oscar hasn't been on the best protocols .  The side effects of preds are numerous but if the protocol is correct then management of the disease and side effects of the preds is very possible and many, many dogs have achieved remission and have never had a relapse again - although there are no guarantees.   The symptoms you describe could be due to an ulcerated stomach because a gastroprotectant wasn't given,  and also the muscle weakness caused by the preds - and this will resolve in time and as many people on this forum will testify the dogs can get back to having a good quality of life and regain most, if not all , their muscle back.

The only way a dog on prednisolone would get Addison's is if the dose was reduced too quickly - but that hasn't happened in Oscar's case.  If by bad luck Oscar has developed naturally occuring (primary) Addison's disease then he should be tested for it asap.

I can really understand why you are feeling so stressed and upset about the situation but Oscar is being treated for his ulcer - I presume (he may need ferrous sulphate if his iron levels are low)  and as he is now off steroids,  I hope his general health and strength will improve.  I do hope he never relapses again but if he does then please reconsider not wanting to go down the steroid route again because if the protocol is correct (and an gastroprotectant is included)  he does stand a good chance of reaching remission.

Jo

Immunosuppressive Protocols for Oral Prednisolone in the Dog.
Ref: Clinical Immunology of the Dog & Cat by Michael J Day  – Professor of Veterinary Pathology, University of Bristol, UK and WSAVA - Chairman of Scientific Advisory Committee.

Professor Michael DayBSc, BVMS(Hons), PhD, DSc, DiplECVP, FASM, FRCPath, FRCVS 



This example is base on a dog receiving an induction dose of 1.0mg/kg/q12hrs

Dose                Duration (based on clinical effect)

1.0mg/kg/q12h             10-28 days
0.75mg/kg/q12h            10-28 days
0.5mg/kg/q12h             10-28 days
0.25mg/kg/q12h          10-28 days
0.25mg/kg/q24h          10-28 days
0.25-0.5mg/kg/ Every other day      at least 21 days
0.25-0.5 mg/kg/ Every third day       at least 21 days


patp

Can I just say a huge well done to you Alicat for fighting Oscar's battle for him. You should be proud of all you have done for him. Hopefully you will get the help you need and he will settle down to enjoy life again.