Max - 11 year old Maltese (Atypical Cushings) - started Lysodren Maintenance Dose

[Janette]

Hello all,

glad I found everyone at "our" new home here.

For those that have been following Max's story, just wanted to let you know that Max has started on the maintenance dose of Lysodren (dosing at the low end of 25mg/kg/week, split into 2 doses).

I am happy :) to report that Max has not had a bad reaction to the Lysodren as far as I can tell. He's had 2 doses so far and the third is tonight (62.5 mg capsule per dose - which I had compounded).

I am relieved that we are through the first week. (I was worried about starting Max on the Lysodren, even at a maintenance dose).

For those unfamiliar with Max's story, we did NOT go through the loading phase because Max's cortisol levels are relatively low. He had been diagnosed as Atypical Cushings and we tried the Melatonin and Flaxseed oil with Lignans route for a year, but it didn't help. I do want to note, that I recently realized that I had been giving Max an extended release type Melatonin pill (had not been evident on the bottle, but found the info on the GNC website). This is NOT what I should have been doing, and I have since changed to another brand. I also was giving Max Flaxseed Oil with Lignans and have since changed to Flax Hulls.

I am continuing both the Melatonin and the Flax Hulls in conjunction with the Maintenance dose of Lysodren.

My plan is to retest with an ACTH stim test in 3 weeks, and we have our fingers and paws crossed that the cortisol levels come down. If not, then I imagine we will increase the dosage.

for reference, below is a recap of his most recent bloodwork:
_____________________________
March 27, 2009 adrenal panel from Univ of Tenn - baseline (baseline normal range) - post ACTH (post ACTH normal range)
Cortisol ng/ml - 22.1 (2.0 - 56.5) - 192.7 (70.6-151.2)
Androstenedione ng/ml - 3.1 (0.05-0.36) - 5.8 (0.24-2.90)
Estradiol pg/ml - 84.0 (23.1 - 65.1) - 91.4 (23.3 - 69.4)
Progesterone ng/ml - 0.11 (0.03 - 0.17) - 2.5 (0.22-1.45)
17 OH Progesterone ng/ml - 0.08 (0.08 - 0.22) - 1.77 (0.25 - 2.63)
Aldosterone pg/ml - 24.8 (11 - 139.9) - 238.7 (72.9 - 398.5)
Comments: these results indicate presense of increased adrenal activity. Values are increased as indicated. The disease has progressed since the last test. Consider items 1 through 5 on the treatment option sheet attached. Traditional Lysodren treatment is probably not needed at this time.
_____________________________

I wanted to say THANK YOU to everyone's input when I was trying to decide which treatment plan to follow.

Janette

[lulusmom]

Hi Janette.

I'm glad you found us and that Max is doing well on his maintenance dose of Lysodren. You are right the cortisol elevation is negligible which leads me to believe the real problem is the sex hormones, especially the estradiol. Changing to the standard Melatonin and Flax Hulls was an excellent decision and I hope that between the three treatments, you will finally start to see some improvements. It may take a bit of time so don't get discouraged because I think you are on the right path.

Glynda

[Squirt's Mom]

Hi Janette,

Sounds like a good plan and I hope you will start to see some real improvements in no time. The melatonin and lignans changes will help, too!

Hugs,
Leslie and the girls

[Bichonluver3]

I have had good luck with regular melatonin and flax hulls. Seems you are on the right track. Keep us updated and give Max a big hug!
Carrol

[Janette]

Hello,

I just wanted to give a quick update - re: Max

He's been on the Maintenance dose since my last posting, but we had worked our way up to Lysodren 62.5 mg three times a week.

Max now weighs 8.5 lbs.

The ASTM stim tests have varied, but the lowest has only been at 11 ug/dL post.

Just did one on March 18th and the results were 3.8 ug/dL pre and 28.1 ug/dL post. The 28.1 post result is the highest result since he started on the Lysodren, so it's obviously not working well.

I have decided to do a full loading on Max (which we never did do since we were hoping a maintenance dose would be sufficient). It won't be for a few weeks yet because I want to time it so I can take some time off from work to watch him.

Other events since I last posted:

Max had his spleen removed on Feb 2010 (ultrasound had shown a small nodule on it, which thankfully turned out to be benign.) As a benefit to having the spleen removed, Max seems more comfortable, with a less tight belly (I would assume that with the enlarged liver, it would be good to have some space freed up :) )

Max has a heart murmur (level 4) and is on spirolactone and enalapril for his heart.

I will post updates as they come.

Janette

[Squirt's Mom]

Hi Janette,

So sorry to hear that Max's cortisol is rising. When his spleen was removed, did they take the whole organ or only a portion? My Squirt also had a tumor but they left half her spleen. I was told it was a very slight possibility that the portion left could also develop a tumor so I wondered about Max's situation with his spleen.

If Squirt's cortisol started to rise even on maintenance, then I would be compelled to do an ultrasound before a load just to be sure there wasn't another tumor somewhere. Have you talked to your vet about this possibility?

That was a scary time with the spleen, huh? I understand! Between the time of learning about the tumor and the actual surgery, I was petrified it would rupture. Every time I picked her up my heart went up in my throat and breathing became difficult I was so scared of making it rupture! :eek: Then she had an acute pancreatic attack right after coming home and had to go back to the hospital for several more days. She is fine and dandy today, tho, and I am so grateful! I'm glad Max has that behind him - and YOU, too! ;):D

Let us know how things are going for him.

Hugs,
Leslie and the gang

[Janette]

Hi Leslie,

With Max, they removed his entire spleen.

While they were in there, they also biopsied the liver which had nodules (related to cushings I'm sure). Thankfully everything came back good news for us, and Max didn't have any unexpected difficulties with the surgery itself. :)

I was a nervous wreck having to make the decision and then waiting to hear the day of the surgery. Recuperation went well - even though Mother Nature decided to complicate our lives with TWO 20" plus snow storms the week when Max came home. :eek:

Poor Squirt, having a pancreatic attack right after her surgery. Misty, my other dog, seems to be prone to pancreatitis - she's been in the hospital because of it twice!!! So I know it can be scary. Glad to hear that Squirt is doing well now.

Janette

[lulusmom]

Hi Janette,

Just checking in on you and Max. How is Max doing today? Did you load him yet?

[Janette]

Hello,

Thank you for checking up and your timing is PERFECT. I was actually just doing some reading on ACTH stim results on the lower side.

I did load Max. We started last Wednesday, and he got 93.75 mg twice a day. (Max weighs 8.5 lbs). His last dose was yesterday (Sunday) morning. I stopped it because he was coughing some and then when I offered him a treat (just in case he had swallowed something wrong like people sometimes do :) ) he didn't take it. That is not Max. So I stopped it.

He had a ACTH stim this morning, and here are the results:

pre: 0.8 ug/dL
post: 1.1 ug/dL

I am glad that we have reached the end of the loading, but he is obviously at the very lower bound, and I am somewhat worried that he will drop a bit lower in the next day or two.

Do you think that is a concern as long as he is eating?

Re: the cough. Max does have a heart murmur (grade IV or V depending on which doctor we see) so I also had them do chest xrays today. No obvious fluid but perhaps a sign of some slight congestion. The regular vet gave me Furosemide 12.5 mg (a diuretic) - Max is to get 1/4 tablet every 12 hours. She has a call into Max's cardiac vet but hadn't heard back from him yet today. She said it's a low dose and a couple of doses wouldn't hurt him and she would rather err on the side of giving it to him for a couple of doses than not give it to him and have his heart start decompensating (I believe that is the word she used). The regular vet also has a call into the IMS we saw a couple of weeks ago but had not been able to make contact with her either. Tonight or tomorrow all of Max's vets should hopefully be able to talk and I know a bit more.

But Max hasn't had any coughing today that I have noticed and he is eating.

My immediate concern is that the post ASTM stim of 1.1 is too low considering his last Lysodren dose was 24 hours before the ASTM stim was done.

Thanks again for checking in on us.

Janette and Max

[lulusmom]

Hi Janette,

Yes that post stim number is low, especially considering the short time frame after the last dose. You need to keep a close eye on Max for signs that cortisol has dropped even lower. If his appetite remains off, that's a definite sign and you should give him a dose of prednisone and take him in to have his electrolytes checked. Your vet gave you Prednisone right?

Please check in with us and let us know how Max is doing over the next 24 hours.

Glynda

[Janette]

Glynda,

Yes, thank you, I do have Prednisone.

As of now, Max IS eating, which makes me feel somewhat okay (Although I think anxiousness is outweighing the okay feeling :().

I will watch him for sure.

Thanks again,
Janette

[Janette]

Just an update on Max:

He IS eating, so that is good. But I can tell his appetite is somewhat on the low side. He will eat his canned dog food, but I haven't seen him eat any of the dry dog food (which is always out for him) and he did not take a dog cookie (whereas he would normally want TWO [or more if he could get them] cookies).

He is a bit on the lethargic side I would say, but he does walk around, and did some sniffing/snuffling around when we were outside on the walk (which I was glad to see - that he was interested in his surroundings).

When I run my hand down his spine, he seems sensitive in certain spots - he has a bad back, so I am sure he is feeling some pain (which I know is to be expected with the lowering of the cortisol).

I contemplated whether or not to give him a dose of prednisone, but ultimately decided to hold off as long as he is still eating at the level he currently is. If his appetite gets worse I can always give him the prednisone....

Working under the assumption that he is in some pain, I gave him Tramadol. I think pain could also be an explanation for the lower appetite and not moving around too much. Hopefully I will see some improvement with the Tramadol.

I did ask the vet before I gave him the Tramadol and also checked that there would be no problem/interaction between the Tramadol and the prednisone in case I do decide to try a dose of prednisone. The vet said that would be okay.

I am hoping that Max feels better tomorrow than he does today. A little improvement bit by bit would be good.

Janette

[Janette]

another update:

I did decide to give him a prednisone - mainly to see if I would notice a marked improvement.

However, when I put the prednisone in his canned food (as I do all his meds), he wanted nothing to do with it. After tempting him with other types of food, Max finally swallowed the prednisone.

An hour or so later, I really couldn't say if I saw any change, so I started worrying more about electrolytes being out of whack.

I decided to take him to the emergency vet to get the electrolytes checked, and the good news is that they seem fine. Specifically:

Na: 159 mmmol/L (normal range is 144 - 160)
K: 4.2 mmol/L (normal range is 3.5 - 5.8)
CI: 114 mmol/L (normal range is 109 - 122)

All good news and will let me sleep better than I did last night......

Janette

[Casey's Mom]

A belated welcome to you from Casey and myself :) Once you are loaded it does get a lot easier. You seem to be on top of things and know what to look for which is great. Just so you know my dog has been on Lysodren for two years now and is doing just fine - it is a life saver.

[Harley PoMMom]

I am happy that Max's electrolytes are within the normal ranges.

The prednisone, from my own prior use, is very bitter tasting. If you should ever have to give it again I would recommend wrapping the prednisone in some kind of lunch meat or cream cheese.

Keep up the great work and keep us posted! :)

Love and hugs,
Lori

[Janette]

Thanks for the welcomes and the good thoughts.

Also thanks for telling me that the prednisone is bitter tasting. That is good to know. I know that the Tramadol is bitter because Max often spits it out :)

I talked to the IMS this morning and she is suggesting I give Max prednisone for the next few days (3 days maximum) and see if he gets to feeling better. And then re-stim him on Monday evening and see where he is.

The current thinking is that, after the stim results come in, we would then start Max on the low end of the maintenance dose range by giving him 31.25 mg three times a week.

So that's the plan.....I will keep posting with updates.

Janette

[StarDeb55]

Janette, I have not posted to you previously. I did want to make sure that you were aware that you really should wait at least 24 hours after giving pred before having a stim done. The pred will read like cortisol on the stim, & give you falsely elevated results.

Debbie

[Janette]

My vet said to fast Max 12 hours prior to the ACTH stim test. They use IDEXX labs for the test results.

I am curious - does everyone else fast their dogs for 12 hours prior? I am Googling the topic and am having a tougher time than I thought finding an immediate consensus..

I am asking because Max has a 5pm stim test scheduled for tomorrow evening so it's very awkward timing if I have to fast him 12 hours. Ten hours would fit into our usual routine....

Janette

[StarDeb55]

My vet required a 12 hour fast on all stims, but told me that it had to be an absolute minimum of 10 hours, if I couldn't get my Harley to do 12. This is really a sample requirement of the lab performing the testing & not the vet.

Debbie

[BestBuddy]

Buddy was never fasted for his ACTH tests. He was diabetic so was fed and had insulin around 6am and tested about 10am.

I assume they made allowances for this in the testing. I was always reminded not to give a fatty meal before the test but Buddy was on a low fat diet so it was never an issue.

Jenny

[Harley PoMMom]

My boy, Harley, was never fasted for his ACTH stim tests. And according to Dr. Mark E. Peterson, a renown cushing's expert, a dog need not be fasted. You can read his blog article here: What's the Best Protocol for ACTH Stimulation Testing in Dogs and Cats?. (http://endocrinevet.blogspot.com/2011/03/whats-best-protocol-for-acth.html)

Love and hugs,
Lori

[lulusmom]

My first dog has been treating for six years and my second for over three years. You can only imagine how many acth stim tests we've done and I've never fasted my dogs. As a matter of fact, if a dog is treating with Vetoryl, you have to give the dog a small meal with their morning dose in order for the acth stimulation test to be meaningful.

[Janette]

Hi all,

I wanted to update everyone on Max. We had another ACTH stim this past Monday night and his results were pre: 1.6 ug/dL and post: 2.4 ug/dL.

Today I started Max on the first dose of a maintenance dose of 31.25 mg that he will get three times a week. Max weighs 8.5 lbs so that is on the low end of the maintenance dose range, but Max loaded very quickly so I feel more comfortable starting low.

I’ve been thinking some about Max’s most recent ultrasound results which mentioned a “nodule” in his left adrenal gland, and also some cysts in his kidneys. The IMS still considered pituitary dependent cushings to be much more likely since Max’s adrenal glands are both normal size. But I guess I am now sort of doing some second guessing…..:(

I think the adrenal nodule bothers me less than the kidney cysts. I say that because if Max’s high cortisol levels are actually caused by adrenal dependent cushings rather than pituitary dependent cushings, I would still treat with Lysodren (rather than elect surgery – due to Max’s heart issues). But I can't help but wonder about the kidneys... The IMS did a mini-renal panel and the results were normal. But I wonder if kidney cysts could raise cortisol levels. Has anyone ever heard anything relating kidney cysts to high cortisol levels?


In case it’s helpful, I’ve compiled the results of Max’s tests / exams from the past month or so.

Max’s Current Medications

Lasix (furosemide) – (for heart issues)
Amlodipine (for heart issues)
Enalapril (for heart issues)
Spirolactone (for heart issues)
Ursodiol (for gallbladder issues)
Lysodren (on maintenance dose now)
Tramadol (for pain relief of back issues, but not on a regular basis though)


3/18/11 ACTH STIM RESULTS

Pre: 3.8 ug/dl
Post: 28.1 ug/dl


3/18/11 BLOOD TEST RESULTS

Only listing HIGH or LOW results:

ALK. Phosphatase: 2263 HIGH (reference range 10 – 150 U/L)
ALT (SGPT): 130 HIGH (ref range 5 – 107 U/L)
TCO2 (Bicarbonate): 25 HIGH (ref range 17 – 24 mEq/L)
Potassium: 6.2 HIGH (ref range 4.0 – 5.6 mEq/L)
NA/K Ratio: 23 LOW (ref range 27 – 40)
Triglyceride: 157 HIGH (ref range 20 – 150 mg/dL)
Auto Platelet: 780 HIGH (ref range 164 – 510 THOUS./uL


4/5/11 ULTRASOUND

Findings: The hepatic parenchyma is diffusely mottled and relatively increased in echogenicity in comparison to the portal structures. A 0.97 cm, relatively hyperechoic, ovoid nodule is noted in the left side of the liver. Echogenic material is present within the gallbladder. Both adrenal glands are normal size and shape, however, a 0.6 cm, relatively hyperechoic nodule is seen in the caudal pole of the left adrenal gland. Multiple linear, relatively hyperechoic striations are seen within the mucousal layer of a segment of small intestine. Marked echogenic foci with distal acoustic shadowing is seen within both kidneys, bilaterally. Numerous nodules and cysts, ranging in size from 0.4-1.9 cm, are present within the kidneys, bilaterally. Some of these structures are anechoic and some are relatively hypoechoic. A hyperechoic focus is noted in the dependent portion of the urinary bladder. No other significant findings were seen.

Conclusions:
1. Mottled hepatic parenchyma with increased echogenicity and generalized hepatomegaly. Endocrinopathy, such as hyperadrenocorticism, is the most likely differential diagnosis. Chronic hepatic inflammation with nodular regeneration or neoplasia, such as hepatocellular carcinoma, are less likely.
2. Left adrenal nodule. Differential diagnoses include adrenal adenoma, myelolipoma or pheochromocytoma.
3. Probable bilateral polycystic kidney disease with bilateral dystrophic renal mineralization. Renal neoplasia, such as cyst adenocarcinoma, is an unlikely differential diagnosis.
4. Cystic calculus.


4/5/11 exam with IMS (Internal Medicine Specialist)

Diagnostic Tests:
• Abdominal ultrasound – normal sized adrenal glands (left one has a small nodule), VERY small cysolith (1 mm); cysts in the kidneys
• Systolic blood pressure – 195mmHg (stressed)
• Urinalysis
[comment by Janette: the only thing identified as HIGH or LOW was the Specific Gravity: 1.010 (LOW) (reference range 1.015 – 1.050). There were no crystals and the pH was 6.0 (reference range 5.5 – 7.0)]
• Urine culture / sensitivity
[comment by Janette: the Urine MIC Culture showed no growth after 24 hours and no growth present after 48 hours]
• Mini-renal profile
[comment by Janette: none of the results were identified as HIGH or LOW, and they checked the following: Total Protein, Albumin, Globulin, Albumin/Globulin Ratio, Urea Nitrogen, Creatinine, Phosphorus, Glucose, Calcium, Sodium, Potassium, the Na/K Ratio was 27 (no reference range given), and Chloride
• 3 view thoracic radiographs (due to crackles ausculted) – no evidence of pulmonary edema (official report pending)


4/13/11 Start date - Max was Loaded using Lysodren for 4.5 days (Max weighs 8.5 lbs, and he got 93.75 mg twice a day


4/18/11 ACTH STIM RESULTS

Pre: 0.8 ug/dl
Post: 1.1 ug/dl


4/20/11 Electrolytes checked

Na: 159 mmmol/L (normal range is 144 - 160)
K: 4.2 mmol/L (normal range is 3.5 - 5.8)
CI: 114 mmol/L (normal range is 109 - 122)


4/21/11 - Cardiac Vet Echocardiogram

• Progressive now advanced degenerative valve disease
• Moderately large mitral regurgitation
• Mild to moderate tricuspid regurgitation
• Mild aortic insufficiency
• Progressive severe left atrial enlargement
• Progressive moderate left ventricular dilation > stable
• Maintained contractility > stable
• Mild systemic hypertension > some signs of high BP on today’s echo
• History of Cushing’s disease > was atypical > now elevated cortisol levels > was loading Lysodren but started coughing stopped eating > rechecked cortisol levels were low
• Mild increase lobar pattern right caudal lung lobe > rule out mild heart failure, airway disease, pulmonary thromboembolism
• Progressive now moderate pulmonary hypertension > rule out secondary to advanced mitral valve disease, secondary to airway disease
• Mild pericardial effusion > unexpected finding > rule out atypical presentation of heart failure, secondary to left atrial tear (my worry), pericarditis, occult neoplasia
• One episode of stumbling/falling over / couldn’t walk > rule out cardiac (arrhythmia, poor cardiac output), neurologic, vasovagal / neurally mediated > no recent episodes
• Change in bark > rule out throat issue – improved with time
• Hind limb paresis / weakness > rule out disk disease, peripheral neuropathy, myopathy associated with Cushing’s disease


4/19/11 – 4/22/11 - For these days, I gave Max prednisone (1/4 tablet of a 5 mg tablet)


4/25/11 ACTH STIM RESULTS

Pre: 1.6 ug/dl
Post: 2.4 ug/dl


4/29/11 - started Max on a Maintenance dose of Lysodren: 31.25 mg that he will get three times a week

[Janette]

Hi,

Just another update on Max - we had another ACTH stim this past Friday and his results were pre: 2.4 ug/dL and post: 11.3 ug/dL.

So obviously being on the low end of the maintenance dose range is not working. (Max is now 8 lbs and is getting Lysodren: 31.25 mg three times a week).

I am contemplating doing a "mini-load" of maybe 2 days (since he loaded quickly in 4 1/2 days last time) and then changing to a higher maintenance dose. I've got a phone call into my vet to discuss the options.

If anyone has any thoughts on a possible approach, I would be glad to hear any ideas.

Thank you,
Janette

[lulusmom]

I think your plan to do a mini load is a good one and I suspect your vet will probably agree. Your experience is a perfect example of how difficult it is to figure out an appropriate maintenance dose. The original loading dose and subsequent maintenance dose were textbook and based on the law of averages, you shouldn't be facing a reload but dang it, sometimes our dogs don't read the book and follow directions. :D

I think your vet is probably correct in thinking that Max has pituitary based disease. A dog with an adrenal tumor rarely, if ever, has normal sized adrenals and an adrenal tumor is highly resistant to lysodren which requires much higher doses and usually longer loading times. With Max loading well before the average 5 to 8 days, I personally don't think he has an adrenal tumor. Of course, if he does have an adrenal tumor, surgery can be a cure so if that is something you would be open to, you can do further diagnostics to make that determination.

Glynda