Cushings conundrum

Re: Cushings conundrum

Jillian Hall — Mon, 02 Nov 2009 09:37:53 GMT

Thanks for everyones suggestions. It's nice to know it seems a genuinely unusual case and that its not just be missing something glaringly obvious!

The dog is coming in on Wednesday for ACTH stim 24hrs post pill. I'll repeat biochem and urinalysis for good measure. I'm also going to offer her an ultrasound. My ultrasound abilities are reasonable. Im not sure I'll be 100% confident identifying small adrenals and saying that they are definately normal, but hopefully an enlarged adrenal will be a lot easier to rule in. I can get myself to the general area of the adrenal and I'll take it from there.

Thanks again for everyones help and I'l make sure I post an update when I get the next results.

Re: Cushings conundrum

Utlendigur — Sun, 01 Nov 2009 23:13:10 GMT

Bsava formulary (and others) says that trilostane can cause adrenal hyperplasia with long term treatment ("but the effects of this are unknown") - might cause problems with ultrasound in distinguishing between hyperplasia and adrenal neoplasia once on treatment. I have wondered with trilostane blocking glucocorticoid synthesis whether this would push increased amounts of precursors down other endocrine pathways? Or whether the unused steroid precursors themselves might have an effect??

Would agree with SG of 1.043 ruling out DI. If SG is getting up to 1.043 is the dog really pupd? What is 24hr intake?

I'd still be wondering whether there was something other (or aswell) as Cushings going on. I would wonder about primary liver disease given the case we saw where we weren't sure whether the pupd, pot belly, hepatomegally and raised liver enzymes were 2e to cushings or actually the primary problem. I suppose for completeness (given virtually everything else has been suggested!) a skin biopsy may give some clues as to the cause of the alopecia

Liked Evelyn's suggestion for the "urine concentration curve" - great tip

Re: Cushings conundrum

Fabian Kaelin — Sun, 01 Nov 2009 20:06:48 GMT

I agree with you Andy, it obviously depends on the owner's finances what test is best performed next. But I definitely wouldn't waste the money or any time on a water deprivation test or fructosamine (assuming the blood glucose was normal and dip-stick did not show glucosuria) for the time being.

Re: Cushings conundrum

Andrew Kent — Sun, 01 Nov 2009 18:05:13 GMT

In my book DI would be out with the SG readings that you've had.

You are right if you have the equipment and money to do it then imaging/endogenous ACTH are the gold standard.

But I think it depends on the financial and clinic situation - HDDST is cheaper and has less complex sampling requirements than endogenous ACTH and adrenals aren't always the easiest to find with a scanner so HDDST still has a place occasionally!

Andy

Re: Cushings conundrum

Fabian Kaelin — Sun, 01 Nov 2009 14:35:13 GMT

Hi Roboxley

Do ADH always respond to Trilostane as well as PDH cases? I think in some cases of ADH surgery to remove the affected gland(s) is the better option than medical management. Otherwise you're right, hunting for other causes may be indicated. Especially since (as you pointed out) ACTH-stim test can be affected by stress or concurrent illnesses, but I think such a high result together with the clinical signs is at least highly suspicious for Cushings, which is why I would look further into Cushings first before hunting for less likely possibilities. And diabetes insipidus I would regard still as unlikely and would be very reluctant to risk dehydration in this dog by putting it through a water deprivation test. Also keep in mind that the dog hasn't only got PU/PD but also pot belly and thin hair coat!

On the last endocrinology course I attended (which was about a couple of years ago) I was told that endogenous ACTH/adrenal ultrasonography was gold standard to distinguish between ADH and PDH and HDDST wasn't performed much any more these days. But I think a LDDST would probably be a good start.

Best wishes

Fabian

Re: Cushings conundrum

Rob Loxley — Sun, 01 Nov 2009 13:44:15 GMT

Hasn't endogenous ACTH measurement superceded HDDST?

Not quite sure how being on trilostane affects any of LDDST/HDDST/ACTH/adrenal imaging??

But if cortisol levels are well controlled over 24hrs and clinical signs are not resolving, surely the hunt is for something beyond classical Cushing's?

Re: Cushings conundrum

Andrew Kent — Sun, 01 Nov 2009 12:06:22 GMT

Equally if ultrasonography is not an option and LDDST isn't conclusive then HDDST may give you a good idea whether adrenal or pituitary.

Andy

Re: Cushings conundrum

Fabian Kaelin — Sun, 01 Nov 2009 11:41:09 GMT

Would an SG of 1.043 not rule out DI in this case? But even PU/PD dogs can in my experience have intermittently fairly normal SG. To then deprive this PU/PD dog of its water is possibly not in the dog's best interest. I once was also told at a CPD that many PU/PD dogs will show some response to desmopressin even if they don't have DI and to only perform a water deprivation test if other causes of PU/PD have been ruled out. In this dog it would make more sense to distinguish between ADH/PDH and confirm it's Cushings first. LDDST , endogenous ACTH combined with ultrasound of adrenal glands should be a good start.

All the best

Fabian

Re: Cushings conundrum

Rob Loxley — Sun, 01 Nov 2009 09:51:49 GMT

Pre-pill ACTH stim would be my next port of call. If normal and given the lack of improvement in clinical signs then either something else is going on as well, or maybe it was never cushingoid - chronic stressfull illnesses can give false positive ACTH, C:Cr ratio and LDDST.

Have diagnosed central DI in a number of pituitary-HAC dogs, unfortunately they've subsequently been euthanased because of progressive neuro signs. Would double check the USG - if it's truly PUPD an SG of 1.043 sounds a bit odd. Having done a few modified water deprivation tests I'd suggest a desmopressin response test instead, once you've checked renal/hepatic/hyperCa/DM/pyelonephritis/elects etc. If the cortisol control is good with trilostane, not sure mitotane is going to help with anything.

Beyond these you're probably looking at abd ultrasound and maybe MRI/CT imaging - or just installing a cat flap so the dog can let it self out to pee, and a large bowl of water?!

Re: Cushings conundrum

Fabian Kaelin — Sun, 01 Nov 2009 01:24:59 GMT

Hi Jillian

Sounds like diabetes mellitus is ulikely as biochemistry is pretty unremarkable (incl glucose). But there may be a possibility of an ADH? May be worth performing (or referring for an) ultrasound of the adrenal glands and measuring endogenous ACTH. Could be surgical case to remove adrenal tumour if confirmed to be ADH? Will also be interesting what 24hrs post Vetoryl ACTH-stim shows - may need BID dosing.

As far as I'm aware diabetes insipidus is pretty rare and in this dog with intermittently normal SG very unlikely. A water deprivation test may be more risky than beneficial.

Hope this helps

Fabian

Re: Cushings conundrum

Clive Ansell — Sun, 01 Nov 2009 00:07:29 GMT

[quote user="Utlendigur"]

Meant to add that with the case above the next step is probably going to be investigating for liver disease (BA stim, ultrasound) + water deprivation test - boss permitting.....

[/quote]

I'm sure he/she will let you run with a water deprivation test (urine concentration curve) and ultrasonography, the only direct cost is yours and your nurses time, and even lab fees for a BAST are not excessive.

Re: Cushings conundrum

Clive Ansell — Sun, 01 Nov 2009 00:04:16 GMT

[quote user="Evelyn Barbour-Hill"]

One tip. When you are explaining to the client what you want to do, don't call it a "water deprivation test". Call it a "urine concentration curve" or something.

[/quote]

Thats a good suggestion, I've never thought of it before. cheers

Re: Cushings conundrum

Evelyn Barbour-Hill — Sat, 31 Oct 2009 20:11:11 GMT

One tip. When you are explaining to the client what you want to do, don't call it a "water deprivation test". Call it a "urine concentration curve" or something.

Re: Cushings conundrum

Utlendigur — Sat, 31 Oct 2009 19:06:04 GMT

Meant to add that with the case above the next step is probably going to be investigating for liver disease (BA stim, ultrasound) + water deprivation test - boss permitting.....

Re: Cushings conundrum

Utlendigur — Sat, 31 Oct 2009 18:32:37 GMT

I've got a similar one. Middle aged border terrier bitch presented with pot belly, thinning coat over trunk, pupd. Biochem unremarkable (as far as I can remember as I haven't got access to notes at home) except probably raised ALP. ACTH stim or LDDST (can't remember which) "consistent with hyperadrenocorticism with compatible clinical signs". Started on 60mg vetoryl (in the days when that was the only strength). Rapid improvement in coat, lot less pupd. Monitoring ACTH stims showed good control. Months later dog began to get very pupd again from about 5pm each day. Tried bid dose and again some improvement but still low sg (can't remember value) and still quite pupd. ACTH stim ok. Just recently (after >2yrs on bid dose) started thinning coat again and increasing pupd. Biochem nad really, ACTH stim showed oversuppression. Also did T4/cTSH which showed very low T4 but normal TSH so probably non-thyroidal. Trialled soloxine anyway but owner said the dog didn't seem well on it so stopped the tablets - coat regrew anyway! Dropped to 60mg sid again and still oversuppressed and again significantly more pupd in late afternoon. Now on 30mg bid and due to repeat ACTH stim soon. Of course, sod's law this dog is on PDSA - boss not happy

We also had another case - again older terrier - which looked cushingoid, pupd, ACTH stim equivocal. The dog had moderately raised ALP and ALT which we initially assumed were 2e to cushings - wasn't started on vetoryl because we were waiting to rpt the tests, then turned out to have a liver tumour so presumbably was pupd because of the liver disease.

Re: Cushings conundrum

Clive Ansell — Fri, 30 Oct 2009 15:04:19 GMT

maybe starved and post prandial glucose levels, urinalysis, and fructosamine to rule out DM. Urine creatinine:protein and creatinine:cortisol ratios may be helpful too?

A long shot, but is iatrogenic cushings possible? no recent or long term steroid treatment?

I guess in an ideal world, ultrasound and MRI of pituitary and adrenal glands would be useful.

I had a case several years ago, a Red Setter that did not respond to Mitotane (pre vetoryl days) It turned out to have a 2cm well defined and encapsulated benign adrenal adenoma that was sucessfully removed at surgery. Complete cure. This was carried out as an exploratory laporotomy as costs were an issue and no diagnostic imaging beyond radiography was available/affordable. Lucky one I guess, as it was going to be pts if nothing was found.

Re: Cushings conundrum

Martin Jones — Fri, 30 Oct 2009 14:40:09 GMT

I'd also be wondering about the possibility of an insulin-resistant DM as part of the Cushings having consolidated into a type 1.

Also the very rare possibility of simultaneous adrenal and pituitary pathologies

Have you tried the old drug? You know the one..... Under the rules of the cascade you could certainly look into it

Martin

Re: Cushings conundrum

Clive Ansell — Fri, 30 Oct 2009 14:07:00 GMT

Tricky one. It seems like you have ruled out all other causes of pu/pd, I assume electrolytes, creatinine, glucose are all normal? A urine SG of 1.043 rules out diabetes insipidus too, as I gather this can occur as a secondary complication due to ADH antagonism. I seem to remember once reading of a case where a pituitary adenoma causing the cushings interfered with or prevented the release of ADH giving rise to a central DI.

Maybe a water deprivation test carried out with care to ensure dehydration doesn't occur?. If results are less than satisfactory, then assess the response to desmopressin.

maybe try twice daily dosing if not doing so already?

Re: Cushings conundrum

Noweia — Fri, 30 Oct 2009 10:24:20 GMT

I have a similar case. A long-standing Cushingoid boxer who is now over-suppressed three ACTH stim tests in a row. I would like to stop treatment but the dog is still PU/PD and polyphagic.

Is your case on once-a-day or twice-a-day treatment?

Re: Cushings conundrum

Hannah Wynne Richards — Fri, 30 Oct 2009 09:44:32 GMT

Glad it's your case, not mine !!!!!

Wynne