May 10 Case Discussion: Dog with anorexia & vomiting

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Kate Richardson — Wed, 09 Jun 2010 09:40:33 GMT

So it follows that a normal PTHrp (assuming normal PTH as well) does not rule out neoplasia?

Thanks

Kate

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Ian Battersby — Wed, 09 Jun 2010 08:55:30 GMT

HI Kate

Great Question-

Mechanisms of hypercalceamia associated with malginancy are suggested as follows.

1- Humoral mechanisms

2- mets of solid tumors into bone

3- heamatological malinagncy in bone marrow.

PTHrp is one of the humoral factors in mechanism one. certainly PTHrp is considered a may player in hypercalceamia of malgnicancy but cytokines are also implicated . I can't remember which ones but TNF- alpha and Beta i think are ones cited.

Most dogs but not all dogs with lymphoma and humoral induced hypercalceamia have elevated PTHrp, but levels tend to be higher with carcinoma. So there is likely to be other factors e.g. cytokines playing a role or working synergistically with PTHrp.

Hope that makes sense

Ian

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Kate Richardson — Mon, 07 Jun 2010 17:20:06 GMT

Can I ask you- is hypercalcaemia secondary to neoplasia always due to PTHrp production or can a neoplasm cause hypercalcaemia in other ways?

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Emma Howarth — Sat, 05 Jun 2010 20:36:17 GMT

Hi all,

Bit disappointed to have missed the last bit as I had no internet / phone reception for the last part of my holiday which has driven me slightly mad!!!

Thanks for taking the time to go through this case with us, Ian. Its been a much more interesting way of learning than reading a textbook. Glad to hear that the case had a positive outcome!

Cheers, Emma

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Roberta Prina — Fri, 04 Jun 2010 19:12:28 GMT

Thank you for the discussion and all the explanations, Ian. It was really interesting!

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Ian Battersby — Fri, 04 Jun 2010 13:45:15 GMT

Hi Roberta and Wynne

spot on.

A and C are clear cut, D is also abnormal as although the PTH is within the normal range it is inappropiately high as you would except the PTH to be at the low normal part of the range in a hypercalceamic patient

Well done and enjoy the weekend

Ian

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Hannah Wynne Richards — Thu, 03 Jun 2010 17:16:55 GMT

Same here c) A, C, D

Wynne

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Roberta Prina — Thu, 03 Jun 2010 13:55:26 GMT

I would choose C (A,C,D)

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Ian Battersby — Thu, 03 Jun 2010 11:21:42 GMT

Options are

a) A

B) A and D

C) A, C and D

D) C ,D andE

E) B and E

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Ian Battersby — Thu, 03 Jun 2010 11:19:53 GMT

Roberta – hit the nail on the head. The biggest concern in these patients is that the other parathyroid’s atrophy. So when you remove the tumor your patient becomes hypoparathyriod and at risk of hypocalcemia. This most commonly occurs within 5 days of surgery but is reported upto 20 days.

A slightly more detailed description is in the case history section.

So thanks everyone for getting involved – I think everyone made some great contributions ( don’t be so hard on yourself Wyn).

I hope you enjoyed it . I know the diagnosis was alittle unusual but what I like about this case is it shows that careful analysis of each test you perform can help you narrow your differentials so that you choose your tests optimally. It also shows that even though the history was brief you can still pull some valuable information out of it when you start to consider your differentials for the problems you identify.

Essentially the problem orientated approach is a process of

1- identifying problems

2- constructing differentials and prioritizing the differential

3- choosing your next diagnostic step based on your most likely differentials

4- Analyzing your results and identify and review your problem list and start the process again.

Once you have made you diagnosis a good habit is to ensure you have explained all the problems you have identified i.e. you haven’t missed anything.

This approach is obviously not applicable to all cases that walk through your door but can help guide you through the more challenging cases.

So we will end with a just for fun multi choice.

Which of the following dogs has tests results suggestive of parathyroid dysfunction. So either hyper or hypoparathyriodism

DOG	PTH	Ionized calcium
	Normal 10-60pg/ml	Normal 1.2-1.35 mmol/l
A	5	0.4
B	23	1.33
C	128	1.98
D	55	1.8
E	32	1.25

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Hannah Wynne Richards — Thu, 03 Jun 2010 10:48:16 GMT

Roberta and Emma I agree with Ian that you are doing brilliantly. I'm consoling myself with the thought that at least I've realised in time that I'm out of my depth and referred b4 it's too late!!!!!!!!!!!!!!!!!!

Wynne

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Roberta Prina — Wed, 02 Jun 2010 20:30:40 GMT

I think that the most important thing to check is the serum calcium level: the parathyroid gland not affected by the tumour is likely to be hypothrophic and not able to produce PTH for some time. Serum calcium level should be checked once or twice daily after surgery. If the hypercalcemia is severe preoperatively or if hypercalcemia has been present for a long period, vitamin D and calcium should be supplemented right after the operation, because there is a higher chance that these patients will develop hypocalcaemia. The other parameters to monitor are the ones related to kidney functions.

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Ian Battersby — Wed, 02 Jun 2010 10:06:40 GMT

Roberta and Emma - great posts.

My thoughts and what I did are now posted in the history, here

We pretty much now have a provisional diagnosis of Hyperparathyriodism based on the ultrasound findings and I did submit a PTH to confirm. Later reported >1000 ( normal 15-60pg/ml)

Surgery is the treatment of choice and the owners did elect for surgery.

My next question to everyone is

Outline your pre, intra and post operative concerns and what treatment options do you have to minimize these risks

Ian

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Emma Howarth — Fri, 28 May 2010 13:40:51 GMT

Clive - Thanks for providing clarity on the ACTH stimulation and steroids debate. I never have quite got that before!

Ian

Significant findings

mild hypernatraemia, normal potassium

hypercalcaemia

azotaemia

mild increase in ALT/ALKP and mild hypercholesterolaemia

haematology within normal limits

urine- isothenuria

The mild hypernatraemia and normal potassium make hypoadrenocorticism less likely (would generally see hyponatraemia and hyperkalemia) although does not exclude this, especially in the face of the recent steroids. However the mild hypophosphataemia makes hypercalcaemia of malignancy / primary hyperparathyroidism more likely differentials.

The mild increases in ALT (essentialy liver specific enzyme), ALKP (non-specific isoenzyme) and mild hypercholesterolaemia may reflect the recent injection of dex, or could suggest some liver involvement in the disease process.

The calcium level appears to have increased further (although this may reflect the use of a different analyser)- so I would be more aggressive re the therapy (already discussed) for this and keeping a close eye on it.

The haematology is normal and therefore less suggestive of bone marrow involvement.

Isosthenuria- this probably reflects the diuresis/ primary disease process.

I would do an abdominal ultrasound at this stage and take aspirates of the liver and spleen for evaluation (again looking for evidence of neoplasia). I would attempt to perform an ultrasound scan of the parathyroids as, if a mass was found, it would be more suggestive of primary hyperparathyoirdism.

As suggested above, the bloods are not suggestive of hypoadrenocorticism, but if I hadn't found anything else I probably do a quick ACTH stim at this stage and exclude it anyway.

If no answers, I would then send a sample for PTH and PTH-rp to try to differentiate primary hyperparathyroidism and hypercalcaemia of malignancy.

Treatment-wise, as stated above, I'd be treating more aggressively re the hypercalcaemia (frusemide and looking at sourcing some calcitonin and maybe biphosphonates). I'd be keeping a close eye on the heart rate and rhythm and ECG alongside the blood parameter monitorong already discussed in the last section.

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Roberta Prina — Thu, 27 May 2010 19:55:21 GMT

[quote user="Ian Battersby"]

Next I would like you to

identify any significant findings
revise your problem list and outline differentials for any new problems identified ( if any)
revise your plan. So the plan will contain what test you want to do next ( and again justify your test selection), your planned monitoring, and treatment

[/quote]

Biochemistry indicate, besides hypercalcaemia and azotaemia, hypophosphataemia, hypernatremia, mildly increased liver enzymes, and hypercholesterolaemia.

I am not sure if the increased cholestorol is significant, since it migt have been caused by the steroid injection. Steroid can also increase ALP serum level.

The most common cause for hypernatremia are GI fluid loss and renal failure. Since our patient is vomiting, this may interfer with a normal sodium serum level.

I think that hypophosphataemia is the most important finding. Its most common causes are: primary hyperparathyroidism, hypercalcaemia of malignacy and DKA.

I think that, at this point, I would like to either rule out or confirm hyperparathiroidism: alternatively to measuring PTH serum level, we can ultrasound the parathyroid glands.

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Clive Elwood — Thu, 27 May 2010 18:03:06 GMT

[quote user="Ian Ross"]Not sure how this works though as surely still get suppression otherwise the LDDST wouldn't work??[/quote]

Forgive me for butting in, but when you give dexamethasone in a LDDST, it supresses ACTH release from the pituitary which then temporarily down-regulates adrenal release of cortisol. If you give exogenous ACTH after dexamethasone in an ACTH stimulation test, this up-regulates cortisol release and you will get a normal response if you have only given one or a few doses of dexamethasone.

With more prolonged exogenous corticosteroid administration you get a more permanent down-regulation of adrenal function and even atrophy (via reduced ACTH release), which means the adrenals cannot respond normally to exogenous ACTH, hence you can get a 'false-positive' diagnosis of hypoadrenocorticism.

Clear?

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Hannah Wynne Richards — Thu, 27 May 2010 17:06:31 GMT

Micheal I find that if I work cases up properly (I'm lucky to have clients who allow me to ) there's very few who actually need steroids. I'm absolutely terrified of using them in horses-most of the ones I treat are Welsh Mountain pony/Sec D types-in other words- EMS types are normal, it's the ones who haven't got it that I regard as abnormal !!!!!!! Either that , or they're elderly-borderline Cushings. The result is I'm terrified of causing laminitis

Ian I'll now read your bit-and try to work out what to do next

Wynne

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Ian Battersby — Thu, 27 May 2010 09:37:37 GMT

What I did and how I justified my decisions is now posted in the history section - click here.

Again I am very glad to see some very comprehensive answers have been posted.

Re the steroid debate- I have a similar line of thinking to Emma - A large number of these cases respond to high rate fluids and then frusemide. If the aim is to achieve a diagnosis then steroids should be avoided. If steroids are used prior to your diagnostics you could get a number of false negative test results. Consequently you may end up doing some tests unnecessarily e.g. Intra- abdominal LN shrink after your steroids, imaging therefore is unremarkable and a PTH assay is run. Leading to frustration but also unnecessary costs in diagnostics.

My feeling would be that the decision to use steroids in a case like this prior to diagnostics should only be after informed consent from the owner. So prescribed only when the owner understands how this will affect future diagnostics and treatment . So if the owner is unwilling or unable to pursue diagnostics and treatment, steroids could be used. However in this case the owner did want to attain a diagnosis so that optimal therapy could be instigated.

I tend to use PTHrp when I have failed to find an obvious neoplasm on imaging and I still suspect it. I tend to run PTHrp when I can't find anything on routine imaging, there are no cytopeania are present and I am considering a bone marrow. The other argument to screening imaging first is the potential delay in obtaining the result.

I didn't run at PTH at this stage as neoplasia was the most likely differential.

So the results of the first tests I performed are posted in the history section now

Next I would like you to

identify any significant findings
revise your problem list and outline differentials for any new problems identified ( if any)
revise your plan. So the plan will contain what test you want to do next ( and again justify your test selection), your planned monitoring, and treatment

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Emma Howarth — Wed, 26 May 2010 21:59:41 GMT

Clearly, in this case, the owner has gone for a referral and wants to do the best for their dog- which means finding out what is wrong and putting it on the optimal treatment. The hypercalcaemia is likely to improve on furosemide and saline (it generally does) so why limit your options?

I would sometimes just use steroids alone in lymphoma- in cases where the owner has no money/ desire to pursue diagnostics. The dog will generally die very soon afterwards; with optimal chemotherapy it may get years of a good quality of life. Its our job to give people all the options- up to them to choose which path they favour given their circumstances...

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Michael Woodhouse — Wed, 26 May 2010 20:45:18 GMT

[quote user="Hannah Wynne Richards"]I NEVER use corticosteroids, unless I'm absolutely driven to do so.[/quote]

Hannah - why the fear of steroids? I would go so far to say that they make a life changing difference to a good number of my patients (large and small).

They try to instil a fear of steroids into us at University but there are many instances where nothing else will do. I have many happier patients because of corticosteroids than I would have without.

I have a few friends who are doctors and they hand them out like sweets with little regard in people - they are not as bad as many make out. Hell, I even give them to horses!

I can't see that with the cascade you don't use a lot of steroids as any kind of practising Vet.

(TBH - if it has lymphoma it is going to die and needs steroids anyway)

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Hannah Wynne Richards — Wed, 26 May 2010 09:48:20 GMT

I NEVER use corticosteroids, unless I'm absolutely driven to do so. At the moment, I have 1 patient in the whole practice on long-term preds-a cat with confirmed auto-immune thrombocytopaenia-even I've been forced to give in on this one. I would use steroids if Addisons was confirmed, or if a neoplasia was confirmed, and the oncologist (I always try to get clients to refer if they want treatment ) includes it in a treatment protocol. Also, if angiostrongylus is confirmed, I would give 7 days steroid during initial panacur therapy, but to give it without panacur and covering antibiotic would be very harmful

Wynne

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Rob Loxley — Tue, 25 May 2010 23:17:56 GMT

[quote user="Michael Woodhouse"]

I'm amazed that none of you have suggested using corticosteroids in addition to the fluids and frusemide. Have I missed some huge contra-indication somewhere?

[/quote]

The difficulty it might cause in your subsequent hunt for lymphoma as a cause of the hypercalcaemia?

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Michael Woodhouse — Tue, 25 May 2010 21:29:14 GMT

I'm amazed that none of you have suggested using corticosteroids in addition to the fluids and frusemide.

Have I missed some huge contra-indication somewhere?

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Emma Howarth — Tue, 25 May 2010 21:13:49 GMT

Hi again all,

Glad I got back before it was all over...our internet connection is very hit and miss!

1. Treatment to instigate now:

0.9%saline - how aggressive I was with this would depend in part history (ie what the dog had actually recieved at the previous practice, hydration status, amount of vomiting, etc). I know suggested rates are up to 180mg/kg/d, but given the breed and age I might be worried about occult cardiac disease and opt for a lower rate, or give boluses and assess response.

Whether I gave furosemide or not at this stage would depend on how adequate I felt the dogs previous fluids had been; but if I felt that they had been reasonable, and the dog was well hydrated and producing urine, I'd probably be electing to start it now.

I'd chose maropitant re emesis/nausea (if needs be- depending on demenour, how often vomiting etc) initially as its licensed/ the dog didn't improve with previous metoclopramide/ it hasn't got renal contraindications as far as I'm aware?? (think it has been reported that metaclopramide can potentially reduce renal blood flow?? so I'd be more cautious about using it in this situation).

2. I'd be monitoring the dog's urine output (catheterised - c below), auscultating its chest frequently and monitoriing heart rate/rhythm, respiratory rate, pulse quality etc. I'd definately want to check the electrolytes (and supplement potassium as needs be). Blood gases would be lovely if we had them... I'd be rechecking urea, creatinine, calcium phos and electrolytes in 24 hours.

3/4. Diagnostic inital tests of choice

I'd probably be running a complete biochem and haematology profile with electrolytes in house initially (not knowing how comprehensive the previous sample had been). I'd also be doing a urine dipstick, specific gravity and in house microscopy on the inital sample obtained.

Since neoplasia is the commonest cause of hypercalcaemia I'd be doing a tumour hunt after this. For example, if globulins were up on the bloods then I'd be doing serum protein electrophoresis, any evidence of any cytopaenia then I'd be wary of bone marrow disease. I'd be having an extra check of the peripheral lymph nodes and anal glands as adenocarcinomas can often be quite small.

If there was nothing to guide me on the exam/bloods then I'd do chest and abdomen survey radiographs. Looking for any evidence masses/lymphadenopathy/ organomegaly. Also checking for any evidence of bone lysis. I'd probably do an abdominal ultrasound (and whilst I had it out have a go at the parathyroids:)!).

That would be my initial choice especially given the fact that the dog is systemically ill (primary hyperparathyoid dogs I've seen have generally only had mild signs) and didn't improve after dex. Bloods eg ACTH stim/ PTH/ PTH-rp would be down the line...

Re: May 10 Case Discussion: Dog with anorexia & vomiting

Hannah Wynne Richards — Tue, 25 May 2010 18:13:22 GMT

1 Treatment Definitely get Ca down, but also make patient feel better. Give 0.9 % Na Cl at 4 ml/kg/hr. Also give metoclopramide-not licensed but I have it on good authority that it is the best for suppressing nausea (as opposed to merely preventing vomiting )

2 Monitoring Ca/K and total protein. Might need to spike fluids with K. If TP (and K )- sufficiently high, could increase fluid rates to 5 ml/kg/hr, and add frusemide 2 mg/kg bid Urea and creatinine

3 Diagnostics PTH and PTHrp Also dogogram to look for tumours, calcified deposits. PTH up and 1y hyperparathyroidism PTHrp up and 2y to malignancy. If angiostrongylus, then might have hint from lung rads. Haematology, as if urea still high with normal creatinine, and also anaemic, then hint of gastric/intestinal haemorrhage, or some other pre-renal type

Wynne