Side effects of large doses of Florinef

[Jo CIMDA]

Hi
You can't look at results from February and relate them to how her thyroid is performing now.  Clearly though the latest results show that her Addisons is not under control, but the february results show that her thyroid was normal at that time.

Blood abnormalities seen in Addison's disease:

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 cases
High Calcium (mild to moderate) – in some cases
ALT- ALP - AST (Mild to moderate increase of liver enzymes) – in some cases

DECREASED:
Low Sodium (Na)
Low Sodium/potassium ratio (K:Na ratio -  less than 27)
Note: 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 cases
Total white blood cell count (WBC) – in some cases
Red blood cell count (RBC or HCT)


There is no reason why she shouldn't have another thyroid test now but to be honest she doesn't seem to be showing classic clinical signs of hypoT. Excessive drinking and weeing and losing weight are not signs of hypoT. 

Clinical signs of hypothyroidism are:
Lethargy, mental dullness, unwillingness to exercise,  stiffness in gait – limping, weight gain (obesity), dry scaly skin, dandruff and/or greasy skin, excessive pigmentation (hyperpigmentation),  skin lesions, on-going ear problems, coat texture and colour changes, loss of hair particularly on the tail and bilateral, symmetrical  hair loss, signs of premature ageing, irregular seasons - poor infertility and libido, depression (tragic expression), irritability or aggression, intolerance to cold, seizures, voice change (pitch of bark),  muscle weakness, megaoesophagus (weakness of muscles in the throat causing difficulty in swallowing).
On examination your vet may also find that a hypothyroid dog has a slow heart beat (bradycardia), eye abnormalities such as corneal lipid deposits or ulceration: dysfunction of the central nervous system (CNS), such as tilting of head, circling, unsteady gait (ataxia):  Blood analysis may also reveal anaemia and high cholesterol.

A dog can have a Polyendocrine disorder but I would like to see her Addison's stable before having a look at other endocrine disorders.

I do hope she is improving on the small increase of Florinef.

Jo

[patp]

Thanks Jo
Sadly no improvement yet. We have been here twice before. She doesn't hold her sodium so the Florinef is increased. That doesn't work so they add in salt. That doesn't work so they add in Prednisolone. That makes her very ill so she has to be slowly weaned off. They then increase the Florinef etc etc etc.

At the moment she is very lethargic, she seeks heat all the time, her appetite is poor, she has started to show aggression, she drinks lots and pees lots and she is very depressed (possibly tragic expression).

[Jo CIMDA]

Hi Patp

It is very frustrating and upsetting when you can't get to the bottom of something like this.  Have you had a full biochemical blood test and a complete blood count done lately?  If you haven't then I would have one done because it might show up something in an area that you are not even thinking about at the moment.

Perhaps she is not concentrating her urine because the Addison's is not stable at the moment (and the kidneys are not able to conserve sodium) but I would still have a thorough blood test done and take it from there. 

As she is very 'down' at the moment and she is on a lower dose of Florinef than she was on previously, I would be inclined to give her 2.5mg of pred every morning until this is sorted out.  At least that way you will know she is having a 'replacement dose' and also it might increase her appetite.  She will go off food if she is low in cortisol and she will be very depressed.  It is such a small dose it shouldn't have any adverse reaction, and especially if she is deficient at the moment. 

It is better to be slightly higher medicated with pred than to be low in cortisol in an Addisonian dog. You can always reduce the dose in a while, but if the body isn't able to produce enough, or if the medication is not adequate, then all parts of her body will struggle.  Her symptoms, to me, seem more Addisonian than anything else, especially with her recent history. Was her dose of Florinef cut from 8 tablets a day to 4 in one go?  Any reduction, unless in exceptional circumstances, should be done gradually, and over a period of time to allow the body to cope and adjust to the change.

Replacement dose for pred is 0.2mg/kg/24hrs.  Give it in the morning.  In normal dogs, that is when the body produces the highest cortisol.

I hope she picks up soon.

Jo

[patp]

Thanks Jo.
She came down from the 8 tablets a day gradually. We reduced it by one tablet per day over two or three weeks.
I take your point that her Addisons is not stabilised. I just can't understand why. We have been working on this for over a year. Every now and then we get a glimpse of the real dog but it never lasts. I hope the referral vet has some answers tomorrow and I will raise the question of supplementing her with pred.

What do you think about supplementing her with salt?

[Jo CIMDA]

Hi

Some dogs have to be supplemented with salt but mostly if the Florinef dose is correct then it isn't usually necessary.  Willow may be one of those dogs who needs some extra salt in her meals. I have just looked up the following reference for you.

Extract from BSAVA Manual of Small Animal Endocrinology:

Salt supplementation:
"Sodium Chloride tablets or salting of the food should be instigated at a dose of 0.1mg/kg/day initially to help correct hyponatraemia but can be phased out and are not usually required long term in most cases.  Dogs requiring unusually high doses of Fludrocortisone, however, may respond to a lower dose of Fludrocortisone if concurrently provided with salt supplementation". 

Good luck tomorrow.  I'm sure it is only a matter of time before she is stable.  chin up!

Jo

[patp]

The vet just rang to say that the thyroid T4 came back as 23 when the normal range is 30 - 100. He considers 23 to be normal for a sight hound. He has sent of some blood for an antibody test on her Thyroid. He explained that this will interfere with the T4 results showing it to be normal when it is not. The results will be back at the end of next week.

Willow's electrolytes are still not balanced with no change since the last test and subsequent increase in Florinef. He has advised that I increase it again to 3 Florinef twice daily. He does not think adding salt to her food will help.

The vet does think that, if the thyroid results all come back normal, that we have a case for applying for a licence to import Percorten.

Willow was quite poorly Thursday night. She vomited during the day and had poo'd overnight though not diarrhoea. She looked awful when the vet saw her on Friday.

She looks slightly better now. I am cooking for her again to try to keep her strength up.

Pat

[Jo CIMDA]

Hi Patp

She may do very well on Percorten and it is certainly worth a try.  The thryoid panel should be TT4, FT4 and TSH, although the TT4 does seem fine for a whippet.

I can't remember if I have said this before but has your vet done a full biochemistry blood test (not just electrolytes) and a complete blood count?  The reason I mention this is,  if an Addisonian dog cannot be stabilised (which is unusual) then the vet should look to see if there is another problem, especially other endocrine disease and it is always best to start with a general, full blood test.

I do hope she picks up soon. 

[patp]

I emailed the vet to ask a question about adding a small dose of Prednisolone to help Willow and this is his reply -

"Dear Mrs Price,

Chiara forwarded me your email as she wasn't sure what we had discussed this afternoon. At present I don't think we should add additional prednisolone, it's certainly an option but there are several reasons why we shouldn't do this at present. Firstly, I'd like to get the electrolytes back to normal, before we change anything else; if we change more than one thing at once it will be difficult to tell what has made a difference to Willow's demeanour. Secondly we have just increased the Flurinef dose, as well as increasing the mineralocorticoid dose to help improve the electrolytes, this will also increase the glucocorticoids that Willow is having so this would hopefully also help, if this is contributing to the problem and lastly when Willow has been on high doses of the glucocorticoids, we have been concern that this may have been responsible for some of Willow's lethargy so I'd hesitate to add this in for the moment. If Willow is stressed or actively unwell, then additional prednisolone would be indicated as usual.

I have asked Chiara to watch out for the thyroid autoantibody results, these should be back later this week. I have attached the electrolyte results for your records. I think we should recheck the electrolytes in 7-10 days time".

He enclosed the blood results -

------------------------------------------------------------------------------------------------------------------
Animal name: Willow                                Sample date: 08/11/2013
   Owner name: PRICE                               Received date: 08/11/2013
Species/Breed: Dog - Whippet                              Report date: 08/11/2013
          Age: 3 Years
          Sex: Female neutered                      Charge:
--------------------------------------------------------------------------------

                          BIOCHEMISTRY
Sample quality             Mildly haemolysed
Total protein              56         g/l            (54 - 77)
Albumin                    33         g/l            (25 - 40)
Globulin                   23         g/l            (23 - 45)
Urea                       6.8        mmol/l         (2.5 - 7.4)
Creatinine                 91         umol/l         (40 - 145)
Potassium                  4.5        mmol/l         (3.4 - 5.6)
Sodium                   * 135        mmol/l    Low  (139 - 154)
Sodium:potassium ratio     30.0                      (>27.0)
Chloride                 * 102        mmol/l    Low  (105 - 122)
Calcium                    2.4        mmol/l         (2.1 - 2.
Magnesium                  0.76       mmol/l         (0.62 - 0.90)
Inorganic phosphate        1.4        mmol/l         (0.60 - 1.40)
Glucose                  * 6.3        mmol/l    High (3.3 - 5.
ALT                      * 101        IU/L      High (13 - 88)
AST                        28         IU/L           (13 - 60)
ALP                      * 110        IU/L      High (14 - 105)
GGT                        2          IU/L           (0 - 10)
Bilirubin                  4          umol/l         (0 - 16)
Cholesterol              * 3.7        mmol/l    Low  (3.8 - 7.0)
Triglyceride             * 0.4        mmol/l    Low  (0.56 - 1.14)
Creatine kinase          * 218        IU/L      High (0 - 190)

                          ENDOCRINOLOGY
T4                         23.2       nmol/l         (13.5 - 50)

                            CLINICAL COMMENTS
Currently euthyroid.

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As you will see, I mis-heard the T4 results!

Pat

[patp]

Willow had diarrhoea overnight and has been vomiting with more diarrhoea today. I have contacted her vet who has advised to just starve her until this evening and then introduce fish or chicken later on this evening.
She did steal another dog's food during a visit we made so hoping it is just that.

[Jo CIMDA]

Hi Patp

I do hope Willow is better by now.  You must be worn out with the stress of it all.

Is Willow's consultant an endocrinologist? If not, it might be worth going to see one.  I don't know where you live but there are a few endocrinologists about and the one that comes to mind is Mike Herrtage at Cambridge University.  Obviously her consultant is considering Polyendocrine disease eg.  hypoT and Addison's disease (dogs with this combination often have low sodium regardless of a high Florinef dose)  but  Willow's glucose is elevated and  I wonder if the consultant has considered other polyendocrine combinations.

It's very frustrating for you.

Jo

[patp]

Thanks Jo. I am utterly exhausted with all the worry.
Willow is under Dick White Referrals in Newmarket. They do have an endocrinologist on the team. He is called Rob Foale and he lectures in Endocrinology at the University of Nottingham. I assume that, in difficult cases, they talk to each other!
I have a sneaking suspicion that Willow was seen as an easy case for an inexperienced resident to handle. I have had to go over her head, on a couple of occasions, to get answers to problems that she was not investigating. They do, however, keep insisting that I see this resident. Perhaps it is part of her studies. So frustrating. I am getting quite emotional about it all and find it difficult to raise the energy needed to fight Willow's corner when faced with a determined vet.
As they are investigating the polyendocrine disease aspect now I am hoping that things will start to move forward again. They have spent the last few months covering the ground already covered by my normal vet!

Hopefully, now that they have covered all the old ground, they will start looking for out of the box answers.

Pat

[Jo CIMDA]

Oh Pat, I can sympathise with your frustration.  If you are going to Dick Whites then you could possibly go to Cambridge.

I want to encourage you to insist that you see the Endocrinologist and if they won't comply then say you want A referral to Mike Herrtage at Cambridge.  At least that way they may sit up and take notice.  You could say that you are finding this whole situation very stressful (which is very true) and the delay in resolving Willow's problem is becoming unacceptable.  I know that sounds a bit like throwing your toys out of the pram but to be honest you should be seen by the best person available and not just an intern. Willow's case is not straight forward.  I know they have to learn but I see no reason why the intern can't sit in on a meeting with the consultant.  Mike Herrtage writes endocrinology text books, so he would be an excellent second choice to Rob Foale.  You are paying the bill so you do have a choice.

I hope this give you more confidence Pat.

Jo

[patp]

Thanks Jo
The vomiting and diarrhoea got worse and I had to call out my own vet. Willow had rallied a bit by the time she got here but she examined her and offered to take bloods to send to Dick White's for the electrolytes to be checked. I said not to worry that I would ring Dick White's in the morning (Tues) and get her in for a lytes check.
I rang and they said Chiara would ring me back.
I gave her a couple of hours and then thought it would be good time to transfer to Rob Foale so asked for a referral to him. I was told that the internal referral would have to come from Chiara and that she would ring me. Ha! I rang back and they paged him at about 2.30pm. He did ring (7.30pm) but I was on the phone and he left a message. I returned his call yesterday but he did not call me back. Willow had improved slightly was eating and drinking, though still with diarrhoea, so I did not chase him up thinking he would ring at 7.30 again. He didn't.

This morning Willow has had diarrhoea overnight and is quite poorly again. I rang Dick White's to ask for an urgent appointment and they said they would page Rob Foale. In the meantime I rang the vet that does Willow's acupuncture, to cancel her appointment, and told her the story. She told me to get Hannah, my vet, to lean on Dick White's. Not sure that she had time to but Rob Foale sent a message to ask me to take Willow in at 2pm.

If this doesn't work out then I will ask for a referral to Mike Herrtage.

Pat x

[Jo CIMDA]

Hi Pat

I hope you got on well this afternoon.  Having said that this response is not good enough and you must start stamping your feet.  No more being polite Pat.  Some referral centres are better than others - just because they are supposed to be 'specialists' doesn't mean you get the best clinicians or treatment. There are definitely better referral centres.

Jo

[patp]

Rob Foale is amazing. He remembered me from Gypsy and knows I am not neurotic!
My head is spinning from all the questions and information that he passed on.
He has admitted Willow to test her for Pancreatitis. I should have an answer tonight.
He is running bloods and hydrating her if necessary. After that he is going to get to grips with her Addisons including considering other steroids to go along with the Florinef.

Will keep you posted.

Pat x