Trixie, 10 y/o Boxer (Possible Calcinosis Cutis; Considering Treatment)

[labblab]

Hi Fred, I'm sure Glynda will soon be back herself, but I don't think she intended for you to feel as though Lysodren (mitotane) would have been a better treatment choice for Trixie in relation to a possibly enlarging pituitary tumor. Even though the only study of which I'm aware that actually documents an increased risk of tumor enlargement was based on trilostane treatment, I've read elsewhere that theoretically the same risk ought to be present with Lysodren treatment, too. The risk seems to relate to disruption of the ACTH feedback loop, and treatment by both trilostane (Vetoryl) and mitotane (Lysodren) results in that disruption. So even though I have not seen any studies that were specifically designed to explore the risk with Lysodren, there is no reason right now to think that the potential should be any different.

I know how the "shoulda, coulda" internal conversaton can eat away at me at times! So on the basis of an enlarging pituitary tumor, I just wanted to spare you any regret about selecting trilostane instead of mitotane (Lysodren).

Marianne

[Squirt's Mom]

Mornin' Fred,

Oh, honey child, you have no grounds to feel as if you may have slighted Trixie or made poor choices on her behalf. If ever informed decisions have been made by a pup parent, they are the ones you have made for Trixie. We can all look back and say, "Oh, I might should have done X" or "Wow, Y would have been the better choice perhaps" but we aren't given the option for do-overs in real life. We simply take what is handed us - or sometimes thrown at us - and do the very best we can with the information we have at the time. And you, my dear, have done and are doing a superb job for your sweet girl. I have no doubt that every night when Trixie closes her eyes she says a silent prayer of gratitude to the Great Dog Above for her very special dad.

Please take care of yourself, too, Fred. We care about your health and well-being, too.

Hugs,
Leslie and the gang

[lulusmom]

Hi Fred,

I'm glad Marianne posted and she is correct. My prior post did make mention that the study I saw inferred that both Trilostane and Mitotane could allow a macradenoma to grow. Mitotane is the same thing as Lysodren so I'm sorry if I confused you. While the study involved dogs treated with Trilostane only, I believe the assumption was made that Lysodren would have the same effect as neither has a direct impact on the pituitary gland. Both do reduce circulating cortisol, thereby eliminating cortisol's negative feedback and increasing the pituitary gland's production of acth. Why are dogs with huge amounts of circulating acth in their blood more likely to see increased growth of a macroadenoma, I don't know and I'm not sure the veterinary community does either.

Glynda

[busyman370]

Looks like I've got some replying to do.

Glynda and Marianne,
After re-reading your post, I saw how I misunderstood what was said. And thanks to both you and Marianne for clearing that up, and for supplying some additional definitive explanation as well.

I will never regret treating Trixie with Trilo. I reviewed my options, did my research, and decided it was the safest and best way to go. And that will forever be that. I have been very pleased with what Trilostane can provide. It's a good, safe and easy to work with drug for treating Cushing's.

And regarding the "shoulda choulda" - How can anyone NOT experience that when trying to treat the conditions we do? Just when you begin to think you've got it nailed, there's a change and you have to almost go back to square one again, and re-think the whole approach, while trying to hit a constantly moving target, and all the while, as Marianne has stated, there are no absolutes. The whole process ends up being a "best guess at best."

And to Leslie and the gang,
Thank you so much for your kindness, understanding and support. After reading what you said about Trixie thinking what a special dad she has before she goes to sleep; I have always felt something like that when I put her and Trudie to bed each night, but just never thought much of it.

But, every night it's a ritual. I let both of them sleep together on their loveseat, instead of their crates, because I think it's easier on trixie to have Trudie there snuggling with her. I have a little comforter that I pull down just a bit over them to help hold in the warmth, without making them too warm, and I talk to both of them, especially Trixie, because as I am sure things are, at times, confusing for her, I want her to feel calm, safe and to know she's cared for, and that everything alright.

My point is that by the way she looks at me when I lay her down and get her into a nice position, and how she completely relaxes in such a trusting manner; it's like she's telling me she absolutely knows how immensely I love her, how I do what I do for her good, and that I never see her as a bother, tells me how much she appreciates how I treat her, and what I do for her.

Then, every night as I am taking myself to bed, I say to them, "Good night, sleep tight, don't let the bug's bite!" That puts a sense of closure to the day, and makes it easier to fall asleep knowing we'll do the whole thing again tomorrow.

Trixie knows she's sick, and I am sure she knows she's not "following all the usual rules," and I believe she does see the extra effort I take away from my day to deal with with her, and I also believe that she knows a condition has overtaken her that she certainly doesn't understand at all, and does experience a certain confusion because of it, but none the less, tries her very best every day to be the best girl she can be. And I know she does that for me.

She knows that I work purposely to make sure she does not feel guilt or shame, and is aware that I understand that she's being the best girl she can be under the circumstances, and how proud I am of her for that.

I treat my dogs as the individuals that each of them are. I see them as a Being, not an object. They're not a human, and I'm not a dog, but we both do have brains, feelings, thoughts, needs and emotions, and once you communicate that to the dog, and that you expect it back, you've created a very good working relationship with them. I ask that they respect me for who and what I am, however, I offer them my respect for who and what they are as well.

I let them be a little bit dog, and they let me be a little bit human! LOL

Of course, I have to make sure Trudie gets brought into the mix too! She's very sensitive to things like that.

And believe me, every day I am so aware that one day, the other shoe will drop, and it will be Trudie that I am caring for. So I really appreciate her having a good life for as long as she can, and with Trixie being so sick, it's even more important for me to try to make life seem as good and normal for Trudie as I can.

Here's a little example; when ever I give Trixie a med, Trudie gets a treat. If I sit down next to Trixie and pet her, talk to her and try to make her feel better, I hold Trudie in my lap while I'm doing it. And I make deliberate efforts to do things that make Trudie know she's special and that I am so happy she's a part of my and Trixie's life.

Being a brindle, I call her "marble cake Trudie." And my thing with Trixie has always been; "did you eat a noodle and turn into a poodle?"

OK, that's enough! LOL

I must say that it's been a pleasure to have this interlude after the road traveled. It's good to think and remember that there still is good through all of this. And there sure is.

I'll be checking in to see of Dr. Peterson replies to Glynda. I still think he will.

Take care all,

Fred
.
.

[molly muffin]

Hi Fred,

I think when it comes to the animals in our lives it is always a two way street. We give and they give, and we take from each other. We comfort each other and we take care of each other. There is no other relationship quite like it.

You get that. Everyone who is here gets that. For those who have never had it, I can only hope that one day they too will get to experience that sense of completeness. It is not something that could ever be regretted in this life.

Hugs,
Sharlene

[busyman370]

Hello All,
Found this while doing a search for any updated info and thought you all would find it interesting.

Seems that they are saying that a lighter weight dog requires more Trilo than a heavier dog would.

I am beginning to wonder if there's such a thing as research overkill!!

It is confounding enough as it is without learning of yet another treatment protocol that challenges everything I've been working with so far.

Ultimately it seems that the ACTH is the only reliable guide, along with how the dog's clinical signs appear.

Here's a snip for you to take a look at:

Keywords:
• Hyperadrenocorticism;Pituitary-dependent hyperadrenocorticism;Trilostane

Background
Trilostane is commonly used in the treatment of dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH). Dose recommendations have varied from the manufacturer and the literature.

Hypothesis
As body weight increases, dose/kg or dosage/day of trilostane required to control the clinical signs of PDH decreases.

Animals
70 dogs with naturally occurring hyperadrenocorticism.

Methods
Retrospective study. Each dog must have been treated for at least 6*months and should have shown a “good response” to trilostane, as determined by owners. Statistical comparisons of dose and dosage were made after the dogs were separated into groups weighing <15 or >15*kg; groups weighing ≤10, 10.1–20, 20.1–30, and ≥30*kg; and then groups based on body surface area versus dose/kg and total amount of trilostane required to control the condition.

Results
There was no significant difference in trilostane dose in mg/kg of body weight or in the total amount of trilostane required daily to control clinical signs, except when the dose for dogs weighing >30*kg was compared with that for the other groups. However, despite lack of statistical significance when comparing groups, there was a significant trend using polynomial regression analysis, suggesting that as body weight increases, the amount of trilostane (mg/kg/dose as well as mg/kg/daily dosage) required to control clinical signs decreases.

Conclusions and Clinical Importance
Dogs weighing >30*kg, and possibly those weighing >15*kg, might require smaller amounts of trilostane per dose or per day than those weighing less, to control PDH-associated clinical signs.

I'm following up with another post, so stay tuned!

Fred

[busyman370]

Here's the follow up post.

Tried my best to get the tables to align, this was the best I could do.

Fred.


Evaluation of the use of baseline cortisol concentration as a monitoring tool for dogs receiving trilostane as a treatment for hyperadrenocorticism.

JAVMA, Vol 237, No. 7, October 1, 2010

From the Department of Small Animal Clinical Sciences, College of
Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843 (Cook); and Dechra Limited, 7015 College Blvd, Ste 525, Overland Park, KS 66211 (Bond).

Presented in abstract form at the Congress of the European College of
Veterinary Internal Medicine, Budapest, September 2007.
Address correspondence to Dr. Cook (akcook@cvm.tamu.edu).

Audrey K. Cook, bvm&s, dacvim, and Karen G. Bond, mph

Objective—To determine whether a single measurement of cortisol concentration can be used to monitor dogs receiving trilostane for hyperadrenocorticism.

Design—Controlled drug efficacy trial.

Animals—103 client-owned dogs.

Procedures—Results of ACTH stimulation tests before and during trilostane treatment were evaluated. Each cortisol concentration after ACTH stimulation was classified as indicative of excessive, acceptable, or inadequate control of adrenal gland function, as outlined by the trilostane manufacturer. Baseline cortisol concentrations before and during trilostane treatment were evaluated; target variables were defined, and sensitivity, specificity, and predictive values were determined.

Results—Results of 103 and 342 ACTH stimulation tests before and during treatment were evaluated. In this population, baseline cortisol concentrations ≥ 1.3 μg/dL accurately excluded excessive suppression (defined by cortisol concentration after ACTH stimulation < 1.5 μg/dL) in 254 of 259 (98%) dogs. In addition, baseline cortisol concentrations ≤ 2.9 μg/dL correctly excluded inadequate control (defined by cortisol concentration after ACTH stimulation > 9.1 μg/dL) in 200 of 211 (95%) dogs. During trilostane treatment, baseline cortisol concentrations between 1.3 and either 2.9 μg/dL or ≤ 50% of the pretreatment baseline cortisol concentration correctly predicted acceptable control of adrenal gland function in 147 of 168 (88%) dogs.

Conclusions and Clinical Relevance—Evaluation of a baseline cortisol concentration collected 4 to 6 hours after trilostane administration in dogs with hyperadrenocorticism provided clinically useful information about control of adrenal gland function. Many dogs receiving trilostane may be adequately monitored without the expense and inconvenience
of an ACTH stimulation test.

Trilostane is a synthetic corticosteroid analogue that competitively inhibits 3-β-hydroxysteroid dehydrogenase; this enzyme is required by the adrenal cortex for the synthesis of cortisol.1 Trilostane currently is approved for use in Europe, Australia, New Zealand, and the United States for dogs with hyperadrenocorticism attributable to a pituitary gland adenoma or an adrenal gland tumor. Periodic monitoring of adrenal gland function is required to prevent inadvertent hypocortisolemia and to ensure adequate control of cortisol release.2,3 Periodic ACTH stimulation tests are recommended so that appropriate adjustments can be made to the trilostane dose.3–7 The manufacturer of trilostane currently recommends a dose reduction when the cortisol concentration after ACTH stimulation is < 1.45 μg/dL and a dose increase when the cortisol concentration after ACTH stimulation is > 9.1 μg/dL.8

It requires at least 1 hour, 2 venipunctures, and 1 injection (IV or IM) to perform an ACTH stimulation test. A dog is usually allowed to remain with its owner or is placed in a cage while the test is performed. A monitoring method that could be completed without requiring that a dog be admitted to a veterinary hospital and with less patient stress and client expense may facilitate compliance with suggested monitoring protocols.

The objectives of the study reported here were to investigate the relationship between baseline cortisol concentrations and cortisol concentrations after ACTH stimulation in dogs receiving trilostane and to attempt to define a range for baseline cortisol concentrations that could reliably be used to rule out the possibility of excessive or inadequate control of adrenocortical function.

Materials and Methods
Animals—A total of 103 client-owned dogs with naturally developing hyperadrenocorticism were used in the study. These dogs were part of a clinical trial to evaluate the efficacy of trilostane. Informed owner consent was obtained for all dogs. The protocol for the efficacy
trial was reviewed and approved by the US FDA.

Abbreviations
CI Confidence interval
NPV Negative predictive value
PPV Positive predictive value

Inclusion criteria for the efficacy trial included appropriate clinical signs, physical examination findings, and clinicopathologic data for hyperadrenocorticism, along with abnormal results on a low-dose dexamethasone suppression test (ie, cortisol concentration at 8 hours after dexamethasone administration, > 1.5 μg/ dL). Dogs with tumors of the adrenal cortex were identified by use of abdominal ultrasonography.

Pretreatment ACTH stimulation tests were performed in all dogs
before the initiation of trilostane administration; dogs with pituitary-dependent hyperadrenocorticism were required to have a cortisol concentration after ACTH stimulation of > 19.9 μg/dL, whereas dogs with tumors of the adrenal cortex were required to have a cortisol concentration after ACTH stimulation of > 14.5 μg/dL.

The cutoff value for dogs with tumors of the adrenal cortex was lower because a substantial proportion of dogs with this form of hyperadrenocorticism have a
more moderate response to exogenously administered ACTH.9,10 Patients with diabetes mellitus, preexisting hepatic compromise, or renal failure were ineligible for the trial; in addition, dogs with distant metastasis of an adrenal gland tumor and that were considered unlikely to survive for at least 12 weeks were also excluded.

ACTH stimulation tests—A pretreatment ACTH stimulation test was performed on each dog < 15 days before starting administration of trilostane. The initial dosage of trilostanea was determined on the basis of body weight in accordance with the manufacturer’s published guidelines.

As part of the efficacy trial, ACTH stimulation tests were performed on days 14, 28, 42, and 84 after initiation of trilostane treatment. Most of the dogs received
trilostane once daily in the morning, but 14 of 103 dogs received doses of trilostane twice daily (morning and evening) during some part of the trial. All ACTH stimulation tests were started between 4 and 6 hours following administration of the morning dose of trilostane, and adjustments to the trilostane dose were determined by use of the cortisol concentration after ACTH stim-
ulation, as described in the manufacturer’s published guidelines.

Each ACTH stimulation test was performed in the same manner. A blood sample was collected for measurement of the baseline cortisol concentration immediately
before administration of a synthetic ACTH product. Each blood sample was placed in a serum separator tube, was allowed to clot at 20° to 25°C for 30 minutes, and
then was centrifuged for 10 minutes at approximately 1,980 X g. Serum was harvested, transferred to a plain serum tube, and refrigerated at 2°C. The synthetic ACTH product was administered IV at a dose of 0.125 mg for
dogs that weighed < 5 kg (< 11 lb) and 0.25 mg for dogs that weighed ≥ 5 kg. A blood sample for measurement of the cortisol concentration after ACTH stimulation was collected 60 minutes after ACTH injection and processed
in the same manner as for the blood sample collected before ACTH administration.

Serum samples were shipped on ice via overnight delivery to a commercial veterinary reference laboratory.c Cortisol concentrations were determined by use of a radioimmunoassay method that involved a gammacounter. A standard curve was created for each assay, and 3 concentrations of commercial (control) cortisol were included at the beginning and end of each assay. The laboratory reportedcortisol concentrations to the nearest 0.1 μg/dL.

Statistical analysis—Data were analyzed by use of a commercial software programd; results were considered significant at values of P < 0.01. When appropriate, data sets were tested for normality by use of the D’Agostino and Pearson omnibus normality test. Correlation between paired data points was determined by use of the Spearman method. Median values of selected data sets were compared by use of the Mann-Whitney U test for unpaired data. Reliability of novel hypotheses was tested by use of the Fischer exact method, with results and 95% CIs provided for sensitivity, specificity, PPV, and NPV.

Initially, the paired cortisol measurements for the ACTH stimulation tests performed 14 to 84 days after the start of trilostane administration were investigated for correlation. Subsequently, each cortisol concentration after ACTH stimulation was reviewed by use of the clinical trial guidelines, and control of cortisol release was classified as excessive (cortisol concentration < 1.5 μg/dL after ACTH stimulation), acceptable (cortisol concentration between 1.5 and 9.1 μg/dL after ACTH stimulation), or inadequate (cortisol concentration > 9.1 μg/dL after ACTH stimulation).

Data pairs were then reviewed, and an attempt was made to identify a baseline cortisol concentration above which excessive suppression of cortisol synthesis could be safely excluded. Similarly, an attempt was made to identify a baseline cortisol concentration below which the possibility of inadequate control of cortisol synthesis could be safely excluded.

Comparisons between the pretreatment baseline cortisol concentrations and results of the ACTH stimulation tests while dogs were receiving trilostane were also performed. An attempt was made to define a percentage decrease from the pretreatment baseline cortisol concentration that might indicate acceptable control of adrenal gland function. This factor was then combined with the newly defined optimal range for baseline cortisol concentration, and the validity of this novel algorithm was statistically determined.

Results
A total of 342 ACTH stimulation tests performed after initiation of trilostane treatment were included in the data analysis. Baseline cortisol concentrations ranged from < 0.2 to 17.7 μg/dL (median, 2.4 μg/dL). Cortisol concentrations after ACTH stimulation ranged from 0.3 to 28.8 μg/dL (median, 4.7 μg/dL). Although the cortisol concentrations after ACTH stimulation typically were greater than the baseline cortisol concentrations, 29 (8%)
cortisol concentrations after ACTH stimulation were less than the baseline cortisol concentrations. There was a significant correlation (r = 0.68; P < 0.001) between the baseline cortisol concentrations and the cortisol concen-
trations after ACTH stimulation, which confirmed a relationship between the 2 values (Figure 1). A total of 103 pretreatment baseline cortisol concentrations were available for analysis. These ranged from 2.1 to 19.8 μg/dL (median, 6.1 μg/dL). This value was significantly (P < 0.001) higher than the median value for baseline cortisol concentrations during treatment with trilostane.

Analysis by use of the manufacturer’s guidelines revealed that the cortisol concentration after ACTH stimulation indicated excessive suppression of adrenal
gland function (ie, < 1.5 μg/dL) in 22 of 342 (6%) samples. The cortisol concentration after ACTH stimulation was within the range for acceptable adrenal gland function (ie, 1.5 to 9.1 μg/dL) in 255 of 342 (75%) samples. Inadequate control of cortisol release (ie, cortisol concentration > 9.1 μg/dL after ACTH stimulation) was detected in 65 of 342 (19%) samples.

Various values for the baseline cortisol concentration were compared with the cortisol concentration after ACTH stimulation (which represented the criterion-
referenced standard) until a range with optimal utility was determined. Excessive suppression of adrenal gland function was best defined by a baseline cortisol concentration < 1.3 μg/dL. Eighty-three of 342 (24%) baseline cortisol concentrations were less than this value. When compared with the cortisol concentration after ACTH stimulation, this value had a significant (P < 0.001) NPV
of 98% (Table 1). In all, 254 of 259 (98%) results were appropriately classified as inconsistent with excessive adrenal gland suppression by use of the cutoff value of < 1.3 μg/dL for the baseline cortisol concentration.

Inadequate suppression of adrenal function was best defined by a baseline cortisol concentration > 2.9 μg/dL. One hundred thirty-one of 342 (38%) baseline
cortisol concentrations were higher than this value.

When compared with the cortisol concentration after ACTH stimulation, this value had a significant (P < 0.001) NPV of 95%. A total of 200 of 211 (95%) results were appropriately classified as inconsistent with inadequate control of adrenal gland function by use of a cutoff value of > 2.9 μg/dL for the baseline
cortisol concentration.

Therefore, the optimal range for baseline cortisol concentrations was defined as 1.3 to 2.9 μg/dL. In this study population, 128 of 342 (37%) baseline cortisol
concentrations were within this range. Of these 128 results, 113 (88%) were correctly classified by use of this newly defined reference range (P < 0.001). Of the 15 incorrectly classified results, the cortisol concentration after ACTH stimulation indicated excessive suppression of the adrenal glands in 5 (4%) and inadequate control in 10 (8%) samples (Table 3). In addition, dogs had a baseline cortisol concentration > 9.1 μg/dL and could have been appropriately classified as poorly controlled on this basis alone.

When the optimal range for the baseline cortisol concentration during trilostane treatment was defined as 1.3 μg/dL to either 2.9 μg/dL or ≤ 50% of the pre-
treatment baseline cortisol concentration (whichever was greater), almost half of the results (168/342 [49%]) were within this range (Figure 2). This range correctly indicated adequate control of adrenal gland function in 147 samples,which yielded a significant (P < 0.001) PPV of 88% (Table 4). In all, 147 of 255 (58%) dogs with acceptable control of adrenal gland function as de- termined on the basis of the cortisol concentration after ACTH stimulation could be identified by evaluation of the baseline cortisol concentration. Sixteen of 21 erroneous classifications were samples in which the cortisol concentration after ACTH stimulation was > 9.1 μg/dL.

The other 5 erroneous classifications were dogs with an unexpectedly low cortisol concentration after ACTH stimulation (1.0 to 1.1 μg/dL,) despite baseline corti- sol concentrations (1.7 to 2.2 μg/dL) within the desired range.

Discussion
It is a general consensus that adrenocortical function should be monitored when dogs are receiving trilostane.2,3 There are 2 principal reasons for such monitor-
ing: to avoid the risk of iatrogenic hypocortisolemia and to ensure adequate control of hyperadrenocorticism.

In the study reported here, we detected a significant correlation between baseline cortisol concentrations and cortisol concentration after ACTH stimulation
measured 4 to 6 hours following trilostane administration in dogs with hyperadrenocorticism. In addition, a range for the baseline cortisol concentration that could be used to reliably indicate acceptable control of adrenal gland function was defined. Therefore, measurement of a timed baseline cortisol concentration may be regarded as a screening test for acceptable control of adrenal gland function; a result within the target range would preclude the need for an ACTH stimulation test in a substantial proportion of patients. For those dogs
with baseline cortisol concentrations outside the defined target range, an ACTH stimulation test may still be necessary before appropriate adjustments in the dose of trilostane are made.

The manufacturer of trilostane currently recommends performing an ACTH stimulation test at 10 to 14 days after starting treatment (or after adjustment of the trilostane dose) and then another ACTH stimulation test at 28 days; tests should be repeated every 3 months thereafter.8 For some clients, achieving full
compliance with these recommendations becomes a financial burden; consequently, visits to a veterinarian’s office for the monitoring tests may be postponed. In addition, a client needs to wait at the clinic for > 1 hour or to leave their dog and return again later. Either option may be less convenient than an outpatient visit and a single venipuncture, particularly if a validated and reliable in-house cortisol assay is available.

Therefore, the authors suggest that use of a baseline cortisol concentration to assess the efficacy of trilostane treatment offers substantial benefits to both owners and patients. However, it is important to regard measurement of baseline cortisol concentrations as a screening test for adequate control of adrenal gland function in clinically stable patients; this technique is not designed to
replace the criterion-referenced standard of an ACTH stimulation test when a more detailed evaluation of adrenal gland function is needed. Limitations of the use of baseline cortisol concentrations to monitor treatment should be carefully weighed by both pet owners and clinicians, and this option should possibly be reserved for patients in which the cost of an ACTH stimulation test is an issue for the owners.

Information regarding a patient’s overall health, including appetite, thirst, and frequency of urination, may substantially influence decisions regarding trilostane dosage.

It would have been ideal to have collected a blinded assessment of each patient’s overall health at the time of every ACTH stimulation test so that relationships between baseline cortisol concentration, cortisol concentration after ACTH stimulation, and clinical status could be examined. However, this was not part of the efficacy study protocol, and retrospective addition of the investigators’ clinical impressions would have been subject to substantial bias. Therefore, we are unable to comment on the clinical status of the 21 dogs with baseline cortisol concentrations within the target range but a low (< 1.5 μg/dL [n = 5 dogs])
or high (> 9.1 μg/dL [16]) cortisol concentration after ACTH stimulation.

Although we were unable to include clinical variables in the data analysis, the importance of this information should not be overlooked. Indeed, it appears likely that inclusion of such clinical data may help identify patients in which measurement of a baseline cortisol concentration is an appropriate screening test,
thereby improving the usefulness of this approach.

It would certainly be advisable to perform an ACTH stimulation test in any patient that was not well (anorectic, lethargic, vomiting, or diarrheic) or that had signs of
hyperadrenocorticism. However, in a patient that had results of a physical examination within expected limits and a recent clinical history of normal thirst, urinary habits, and appetite, evaluation of a baseline cortisol concentration may provide sufficient information. On the basis of our findings, a healthy dog with a baseline cortisol concentration between 1.3 μg/dL and either 2.9 μg/dL or ≤ 50% of the pretreatment baseline cortisol concentration may safely continue to receive the current dose of trilostane. In addition, a baseline cortisol concentration ≥ 1.3 μg/dL could reliably exclude the possibility of an overdose of trilostane in an ill patient or when a patient is reevaluated following a reduction in the dose of trilostane.

We chose to use the manufacturer’s guidelines regarding the cutoff value for inadequate, acceptable, and excessive adrenal gland function for this study. However, there currently is a lack of consensus about the optimal range for the cortisol concentration after ACTH stimulation for dogs receiving trilostane, and various recommendations may be found in the veterinary literature.3–7 The guidelines we used may still be useful, but they may need to be modified on the basis of one’s definition of acceptable control.

We did not attempt to identity the small group of dogs that received trilostane twice daily and do not know whether this may have influenced our results and
conclusions. It has been suggested that twice-daily ad- ministration of trilostane may improve clinical control and decrease the required total daily dose.7,11 Because both basal cortisol secretion and the response to administration of exogenous ACTH are proportional to plasma trilostane concentrations, it appears unlikely that variations in dosing frequency would substantially influence our findings. However, further studies may be necessary before this conclusion can be made with confidence.

The timing of blood collection in relation to the administration of trilostane is much more likely to impact the value of our technique. Results of the study reported here confirmed a relationship between baseline cortisol concentrations
and cortisol concentrations after ACTH stimulation for dogs receiving trilostane. In addition, our findings suggest that a baseline cortisol concentration measured 4 to 6 hours after trilostane administration may be a useful monitoring tool in dogs with hyperadrenocorticism.

Additional studies that incorporate subjective information about patient status (eg, thirst, urination, appetite, and coat condition) may help to clarify the clinical utility of this technique.


Cortisol concentration after ACTH stimulation

Baseline
cortisol <1.5 1.5 to 9.1 <9.1
concentration μg/dL* μg/dL† μg/dL‡ Total

<1.3 μg/dL* 17 65 1 83
1.3 to 2.9 μg/dL† 5 113 10 128
>2.9 μg/dL‡ 0 77 54 131
Total 22 255 65 342

Values reported are the number of samples with the indicated cortisol concentrations.

*Considered indicative of a dose of trilostane that resulted in excessive suppression of adrenal gland function.

†Considered indicative of a dose of trilostane that resulted in acceptable control
of adrenal gland function.

‡Considered indicative of a dose of trilostane that resulted in inadequate control of adrenal gland function.

Results of 342 ACTH stimulation tests performed on dogs with hyperadrenocorticism 4 to 6 hours after trilostane administration, categorized on the basis of a specified baseline cortisol concentration and the cortisol concentration after ACTH stimulation.

Baseline cortisol concentrations and cortisol concentrations after ACTH administration for 342 ACTH stimulation tests performed in dogs with hyperadrenocorticism 4 to 6 hours after trilostane administration. Results are plotted on a logarithmic (base 2) scale. Range of baseline cortisol concentrations (1.3 to 2.9 μg/dL [vertical lines]) and cortisol concentrations after ACTH stimulation (1.5 to 9.1 μg/dL [horizontal lines]) considered indicative of accept-
able control of adrenal gland function are indicated.

Cortisol concentration after ACTH stimulation

Baseline
cortisol >1.5 1.5 to 9.1 >9.1
concentration μg/dL* μg/dL† μg/dL‡ Total
> 1.3 μg/dL* 17 65 1 83
1.3 to 2.9 μg/dL 5 147 16 168
>2.9 μg/dL‡ 0 43 48 91
Total 22 255 65 342


Values reported are the number of sam0les with the indicated cortisol concentrations.

*Considered indicative of a dose of trilostane that resulted in excessive suppression of adrenal gland function.



a. VETORYL, Dechra Veterinary Products, Overland Park, Kan.
b. Cortrosyn, Amphastar, Rancho Cucamonga, Calif.
c. IDEXX Reference Laboratories Inc, North Grafton, Mass.
d. GraphPad Prism, version 5.01, GraphPad Software Inc, La Jolla,
Calif.
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[Steph n' Ella]

Wow! Lots to think about!

[Squirt's Mom]

Hi Fred,

It's been a while and I am wondering how YOU are and how Trixie is. When you get a chance to update, that would be wonderful.

Hugs,
Leslie and the gang

[Lady's mom]

Glad you posted this. I've been wondering about them also.

[busyman370]

Hi Squirt's Mom and Lady's Mom!
Thank you so much for your interest in us. I do appreciate it.

I have been busier than I'd like to be, but it all has to be done. I am closing on a new home sometime during the first week of November. The real estate process has been long one, but ended well for all involved.

I have been wanting to get us out of this two story colonial and into a one floor ranch home for quite a while, but the years of one dog getting sick, then dieing, only to be followed up on the average of six months with another one getting sick and dieing has kept me here. I did not want to put my dogs through the trauma of moving to a new home, especially at their advanced ages.

When I realized that I had managed to pull Trixie out of what would have been certain death, had she been with someone else who was not as dedicated as I was in regard to doing anything and everything to help her, I decided to jump back into the real estate market and get us into that one floor home.

Our new home will give us all an advantage right off the bat as the steps leading from the deck, which is even with the floor as you step out and on to it, only has two steps down and you're on the lawn. The house I have now has five, and when a dog is not at it's best health, that is a big negative in my book. Plus we can all sleep at least on the same floor, probably in the same room.

Trixie and I have been on quite a ride, to say the least!

I almost can't believe some of the near misses Trixie and I have encountered along the way, and how fortunate I've been to stumble onto some of the things I did that absolutely helped her continue to fight and struggle onward, not only through her Cushing's, but all the ancillary conditions that accompanied it as well, while all the while having to deal with all that comes with being a ten year old Boxer dog!

She had more than one challenge to deal with, and her age posed a continual threat to each and every attempt to deal with the various illnesses that were trying to overcome her.

Once we got through the beginning phase of treating the Cushing's, which was getting the Trilo dose established and controlling her pu/pd with desmopressin, and her thyroid with soloxine, it became a fly by the seat of your pants endeavor, calling on all the strength of analysis that I had.

As you all know, I've changed up her Trilo a number of times, and other than the establishment of the first dose, my Vet has been no help at all. I found it to be simply a waste of time to try to get him involved as he just didn't know much about the intricate nuances of treating a Cushinoid dog, and had no working knowledge of using Trilo.

He did consult with a specialist once, and the specialist was wrong! I was concerned about Trixie's pu/pd, and why the Trilo hasn't corrected it after over six months of therapy. The specialist said that the pu/pd after such a long period of time suggests that her brain tumor is large and is the cause.

Of course, I had no recourse but to believe that diagnosis and proceed accordingly by upping her Desmopressin. It did control her pu/pd, but as time went on I noticed that she was exhibiting symptoms that could easily be blamed on a brain tumor, but from my observance, I just was not convinced that the brain tumor was the cause. She acted too normal in other ways.

So, once again I took matters into my own hands. I researched her symptoms - AGAIN - and recalled the side effects of Desmopressin, and she was exhibiting almost all of them. The confounding part of this is that they are basically the same symptoms you would see from a brain tumor, such as head shakes/seizure, swallowing problems, just to name two.

The biggest kicker was that I believed that although her pu/pd was being controlled, I was concerned that she was not drinking enough, and being under-hydrated could cause convulsive muscles, and or seizure like activity, including head shaking, also producing an imbalance in her electrolytes, which can contribute to the condition.

Also, she had a look in her eyes that suggested her stomach was upset, I saw that look before in one of my females who was suffering from stomach cancer, and her ability to swallow was getting worse. I had to push her meds down her throat.

Doubting that the brain tumor was as responsible for her symptoms, as the experts indicated it was, I immediately dropped her Desmopressin from 4.5, 0.1 mg tablets given three times per day down to 3, 0.1 mg tablets given three times per day.

As much as her prior dose of desmopressin did work well for her pu/pd early on, I now suspected that the Trilo may have helped her heal, and had silently also corrected her pu/pd.

That would make the once beneficial dose of desmopressin to now become a very toxic one for her.

Just to be on the safe side, and in trying to remove anything that could be contributing to her condition, I stopped giving her digestive enzyme with her meals. I had just opened a new bottle and considered the possibility that it may have been a "bad batch" and could be contributing to her upset stomach.

I saw almost immediately that she was drinking a bit more, but her urinating was not excessive nor anywhere near being "uncontrolled."

This told me to drop her desmopressin dose ever further, so I reduced it to only 1/2 of a 0.1 mg tablet, and stayed with the three times per day dose.

She began to drink much much more, yet no pu/pd!

That was a shocking experience as I realized that the Trilo had corrected her pu/pd probably sometime ago, but since she was on the Desmopressin, I didn't have a clue as to when the pu/pd was resolved!

She is now properly hydrated for sure, and other than a few things like her being less than robust, having some very minor and infrequent muscle contractions during sleep, and is mostly more interested in sleeping and or laying on her couch, she is very close to normal in all other ways.

She is very interested in eating, she is on a regular schedule of her potty's - just like clockwork, and seems to be in overall comfort and does have a quality of life.

Since her poops are very normal and regular, I am not going to give her the digestive enzymes anymore. I feed the Wellness Lamb and Rice Super 5 dog food, and it's one of the higher end holistic foods. I trust that the digestive aid ingredients are sufficient enough, as the past has proven with all my dogs that have been on the food. In fact, I used to feed a raw diet, and this food is way better! I've never had any Boxer's live as long as Trudie and Trixie have. To me that's proof enough. Trudie is still like a puppy, and Trixie is trying to be! Trudie and Trixie were started on the Wellness, but my other dogs were only introduced to it when they were around the age of seven years on average.

Actually, she's been doing better without the digestive enzyme than she was with it.

Also, I have to remember that she is a TEN year old Boxer, and had been through a lot of damage to her body, and probably her mind as well.

With this realization, I make my evaluations of her accordingly.

I am considering taking her off the Desmopressin all together, but feel that since the 1/2 tablet dose does not seem to be effecting her with any negativity, I think it's smart to keep her on that extremely low dose until she has had a nice period to time to adjust to our new home environment. However; I may take her off sooner and see how she does.

Since I will own two homes at the same time, I will shuttle them back and forth so the change will be a gradual one. Then by the time I actually sell our current home, both Trixie and Trudie will be all settled in at their new home.

One other thing about Trixie; almost every time she goes out to potty, after she's done, she always trots around the yard, and on many occasions actually tries to run! Kind of a rocking horse gallop. I really enjoy seeing her do that as it tells me that her body is functioning well, and that she is feeling well and even though she is ten years old and her body has been broken down by her illness, she can still bring out the puppy in her as she enjoys the feeling of wanting to run!

The other day, Trudie was break dancing on the carpet, and Trixie walked over to her and - in Trixie terms - was attempting to play with her. Trixie basically just stood over her and did something that looked like she sort of stumbled into Trudie, but I saw that as Trixie was stimulated enough to choose to engage in a sort of play mode, which again suggests that she's not ready to hang it up yet!

So, that's the latest update on Trixie.

For myself, I am trying like hell to get all that needs doing to get done ASAP as I need to go in for a scan on December 4th to see how my aneurysm is doing.

If it has enlarged to the point where the surgeon recommends surgery, then I will have to make a decision. I really don't want to have to go through surgery and the recoup time just yet. I am hoping that I can buy just a bit more time so I can get us and everything else concluded and settled first.

My current property should sell well and quickly, but not in the winter months of December, January, February and at least half of March, so I really would like to conclude the sale process, and make sure my dogs are all settled, and have some reliable people lined up to care for my dogs, before I consider having surgery.

Hopefully the scan will show that I'll have the time, and I won't have to make the decision to put it off for at least a few more months, because if I need to put it off, I will.

Frankly, going by my own research on the numbers and ratio of potential growth, I do not feel that my December scan will show anything requiring immediate response.

So, once again, another of my loquacious posts! LOL

Hope you are well and things are good in your lives.

Take care and thanks again for the show if caring.

All the Best,
Fred, Trudie and Trixie.
.
.
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[molly muffin]

hi Fred Trudie and Trixie,

Well you should be closing or just closed on your new home. Can't say enough about how wonderful it will be when you don't have to do the stair thing any longer. (we'll still be climbing her for quite a while longer probably)
Just wanted you to know where thinking of you during this busy time. Hope all Your tests come back well too. December right?
That is so great that Trixie is doing well. :) Love that running gallop through the yard!

Sharlene and Molly Muffin

[Squirt's Mom]

Been too long....how are you and Trixie doing, Fred? Let us hear from you when you can!

Hugs,
Leslie and the gang