Max - 14/15 yr old Maltese - kidney issues - debating continuation of Lysodren

[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?.

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.

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

[Janette]

Hello,
It's been a while since I've posted. Maxwell is now approx 14/15 years old. Maxwell has been on maintenance doses of Lysodren with some mini loads to keep his values in the target range. The most recent of which were Jan 13th and 14th, 2012 (a 2 day mini load), and then a one day mini load on Feb 4th, 2012. I think the Feb 4th one was a mistake on my part - but I had skipped a few maint doses and wanted to make sure Max's cortisol levels didn't climb too high. I think I should have totally stopped the Lysodren a couple of weeks ago. My main concern is that Max has been having a low appetite for about three weeks now.

HOWEVER I have now stopped giving Max Lysodren (as of this past Saturday).

On January 23rd, he was obviously not wanting to eat (not even treats) so I took him into the vet for a check up. At that point I was more concerned that he might be having some back pain and not wanting to eat (Max has a history of back pain, and had surgery for a ruptured disk in April 2008), and I also was concerned that maybe his cortisol levels were low (Max has Cushings and is being treated with Lysodren). We did an ACTH stim test (the results came in the next day: Pre: 3.2 ug/dl and Post: 6.2 ug/dl - so too low cortisol levels didn't appear to be the case), and the vet examined Max and he seemed to be a little protective of his neck so we tried a few days of an anti-inflammatory (meloxicam) in case he was suffering disc pain.

A week later Max still wasn't eating well so I took him in for more blood work and a urinalysis, the results of which I have included at the end of this post.

After the blood test results came in, the vet also suggested doing an abdominal ultrasound to see what else might be going on. The ultrasound was done on 2/3/12 and noted multiple cysts in the kidneys. I have included the ultrasound report at the end of this post.

The vet's assumption was that Max's kidneys are functioning less and less well, and that this is leading to his lack of appetite.

The last thing I would like to point out is that this past Saturday morning Max refused to eat anything (no chicken, no hotdogs, no eggs). He had also thrown up a little the night before and had diarrhea as well - all of which was very worrisome to me. I placed a call into the vet and while I was waiting for her to be able to call me back I did some web research re: kidney disease, and came
across something that mentioned a low NA/K ratio could indicate Addisons, and that all of a sudden made me realize that maybe I was being side tracked by the kidney issues - when maybe it WAS low cortisol levels. So I gave Max a "rescue dose" of prednisolone. When the vet called me back she had said she had also been wondering if it was the cortisol levels and she agreed that giving the prednisolone was a good thing. She also prescribed something for the diarrhea,
which I went to pick up from the vet (taking Max and Misty along for the car ride). When we got back home, Max actually ate some chicken (yeahhh!!) - so I am of the opinion that the prednisolone helped him feel better.

I gave him another dose of the prednisolone the next day, and have stopped giving him any Lysodren (maintenance dose) for the treatment of his Cushings.

So...... the low appetite problem still remains an issue. For about the past week, he has been only eating people food for the most part. Initially (three weeks ago) I could mix some chicken up with his dog food (prescription diet: Royal Canin Urinary S/O to prevent formation of bladder stones which he had surgery to remove back in Nov 2006), and Max would eat the dog food along with the chicken. Then it progressed to where he wouldn't eat the Royal Canin Urinary S/O but he would eat some other dog food (he did okay with Canidae for a few days), and now he won't eat the Canidae anymore either. Chicken breasts so far have been something he will eat but I worry that soon he will refuse that as well.

Last note: the vet did prescribe Mirtazapine as an appetite stimulant and I gave Max 2 doses of it initially. However I couldn't notice an appreciable increase in his appetite, and I did notice that he seemed a bit more wobbly in his hind end (which is already pretty wobbly - I think as a combination of his back surgery and the cushings reduction in muscle mass) so the vet had suggested maybe stopping it and seeing if his appetite got worse. After this Saturday morning not eating issue I decided to start Max back on the Mirtazapine, and he had his first dose on Sunday. The vet said to give it to Max every other day, so he was supposed to get another dose this morning but I forgot to give it. I apparently haven't worked the Mirtazapine into Max's pill regimen sucessfully yet (I have listed all of Max's medications as part of my signature line below).


Max's kidney blood test results don't seem to be too bad based on what I've researched so far, and I posted a similar post on the yahoo K9Kidneys forum/list and a few of the moderators there also said that Max's kidney values don't look too bad (in terms of chronic kidney failure) and they were of the opinion that I should look at Max's Cushing meds and also perhaps Max being Addisonian now. <-- However Max's last stim test was at a post 6.2 so I assumed that his cortisol levels were not the cause of his low appetite.

My plan is to stop the Lysodren for a few weeks at least and see if Max's appetite returns.

I would be appreciative of any opinions and/or suggestions as to what I could try next - either in terms of additional vet tests and/or supplements/foods to try with Max.

Sincerely,
Janette & Maxwell (Maltese, 8 lbs, 14/15 years old, kidneys with cysts, Cushings [Atypical at first, then seemed to change to Typical], Heart Murmur, history of back pain) in Frederick, MD
Max's medications: for cardiac issues - enalapril, spirolactone, amlodipine, furosemide, aspirin; and for prevention of bladder stones he is taking Ursodiol; for treatment of Cushings - Lysodren (although have currently stopped until his appetite gets better); for lack of appetite: famotadine and starting Mirtazapine


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Superchem
Format:
Description - Date 1/6/2012 - Date 1/30/2012 - (Ref Range)
Glucose - 105 - 93 - (60 - 125 mg/dL)
Bun - 33 - 57 - (7 - 27 mg/dL)
Creatnine - 1.4 - 1.8 - (0.4 - 1.8 mg/dL)
TotProtein - 6.6 - 7.2 - (5.1 - 7.8 g/dL)
Albumin - 3.3 - 3.5 - (2.5 - 4.0 g/dL)
TotBillirub - 0.2 - 0.2 - (0.0 - 0.4 mg/dL)
AlkPhos - 1010 - 1060 - (10-150 U/L)
ALT - 313 - 144 - (5 - 107 U/L)
AST - 68 - 38 - (5 - 55 U/L)
CK - 118 - 76 - (10 - 200 U/L)
GGT - 10 - 5 - (0 - 14 U/L)
Cholesterol - 193 - 188 - (112 - 328 mg/dL)
Calcium - 10.2 - 10.9 - (8.2 - 12.4 mg/dL)
Phosphorus - 4.5 - 4.9 - (2.1 - 6.3 mg/dL)
Sodium - 143 - 149 - (141 - 156 mEq/L)
potassium - 5.6 - 5.7 - (4.0 - 5.6 Meq/L)
chloride - 100 - 105 - (105 - 115 mEq/L)
Albumin/Globulin ratio - 1.0 - 0.9 - (0.6 - 1.6)
BUN/Creatinine ratio - 23.6 - 31.7 - (no ref range provided)
Globulin - 3.3 - 3.7 - (2.1 - 4.5 g/dL)
tc02-bicar - 25 - 29 - (17 - 24 mEq/L)
NA/K ratio - 26 - 26 - (27 – 40)

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CBC
Format:
Description - Date 1/6/2012 - Date 1/30/2012 - (Ref Range)
Hemoglobin - 12.6 - 13 - (12 - 18 g/dL)
Hematocrit - 37.2 - 39.9 - (37 - 55 %)
WBC - 7.4 - 9.5 - (5.7 - 16.3 K/uL)
RBC - 5.96 - 6.17 - (5.5 - 8.5 M/uL)
MCV - 62 - 65 - (60 - 77 fL)
MCH - 21.1 - 21.1 - (19.5 - 26.0 pg)
MCHC - 33.9 - 32.6 - (32 - 36 g/dL)
Platelet Count - 837 - 759 - (164 - 510 K/uL)
Remarks - Slide reviewed microscopically. No parasites seen.
Neutrophils - 58 - 61 - (60-77 %)
Lymphocytes - 25 - 23 - (12-30 %)
Monocytes - 10 - 11 - (3-10 %)
Eosinophils - 7 - 5 - (2-10 %)
Basophils - 0 - 0 - (0-1 %)
Absolute Neutrophils - 4282 - 5795 - (3000 - 11500 /uL)
Absolute Lymphocytes - 1850 - 2185 - (1000 - 4800 /uL)
Absolute Monocytes - 740 - 1045 - (150 - 1350 /uL)
Absolute Eosinophils - 518 - 475 - (100 - 1250 /uL)
Absolute Basophils - 0 - 0 - (0 - 100 /uL)


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URINALYSIS
Date : 1/30/2012
Description - Test Result - (Ref Range)
Collection Method - Free-Catch
PH - 5.5 - (5.5-7.0)
Specific Gravity - 1.016 - (1.015-1.050)
Appearance - Hazy - (Clear)
Color - Yellow
Protein - Negative - (Neg)
Glucose - Negative - (Neg)
Ketone - Negative - (Neg)
Bilirubin - Negative - (Neg to 1+)
Blood - Negative - (Neg)
WBC - 2 - 5 - (0-5 HPF)
RBC - None Seen - (0-5 HPF)
Bacteria - None Seen - (None)
EPI CELL - 1 + (1-2) - (0 )
Mucous - None Seen - (None - 2+)
WBC Casts - None Seen

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URINE CULTURE & SUSCEPTIBILITY
Date: 2/3/2012
Source: Urine
Status: Final
Completed Culture Results No Aerobic Growth

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ACTH STIMULATION

Format:
Description - Date 1/6/2012 - Date 1/23/2012 - (Ref Range)
Pre-ACTH Cortisol - 2.4 ug/dL - 3.2 ug/dL - (1 - 5 ug/dL)
Post- ACTH Cortisol - 12.4 ug/dL - 6.2 ug/dL - (1 - 5 ug/dL)

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ULTRASOUND
Date: Feb 3, 2012
HISTORY: Rule out an neoplasia
PROCEDURE: Abdominal ultrasound

FINDINGS:
Both kidneys are irregular and enlarged secondary to large anechoic round cysts measuring up to 3.7 cm x 3.1 cm (left renal cortex) and 0.6 cm x 0.7 cm (right cortex). The visible renal cortex is hyperechoic with decreased corticomedullary distinction. The liver is homogenous with normal echogenicity and size. The gallbladder is moderately enlarged with no abnomalities detected. The common bile duct and pancreas is not visible. The adrenal glands measure within normal limits with normal morphology. The gastrointestinal tract is unremarkable with normal wall thickness and retention of layering. The urinary bladder is collapsed with no obvious abnormalities detected. There is no evidence of lymphadenopathy or peritoneal effusion. The remainder of the visible abdominal study is within normal limits.


CONCLUSION:
Bilateral renal cysts, much greater on the left side. Chronic renal changes are detected. No other abnormalities detected.

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[Cyn719]

Janette and Maxwell

Thanks for the update and his present history. So sorry Maxwell is not feeling well. You know the members here will be by to help you soon. Hang in there.....we are all here for you.

Hugs xoxo

[Harley PoMMom]

The rule of thumb is if a dog is not acting like him/herself than the Cushing medicine should be stopped. So I do agree with your decision of stopping the Lysodren.

The Yahoo K9kidney forum has a great bunch of people that are very knowledgeable about kidney disease so I am happy that you are joined there.

When a dog has Cushing's and then a kidney issue arises it is a catch 22 situation as to whether to continue treatment. Whatever decision you make we will be here to lend moral support.

Is Max losing protein in his urine? Has an UPC been done?

Sending loving hugs,
Lori

[Janette]

Is Max losing protein in his urine? Has an UPC been done?

Lori,

Hmmm, re: losing protein - the urinalysis said protein "negative" so I assume that means he is not losing protein......(???) Do you think that is a correct assumption?

re: the UPC being done? Googling UPC I think you are asking about a urine protein:creatinine ratio test? No, that test has not been done.
Do you think it would be worth having done?

Janette

[Harley PoMMom]

Sometimes an urinalysis will not detect protein-loss. If a kidney issue is being contemplated, an UPC (Urine Protein:Creatinine Ratio) test should be performed because this test will detect the smallest amount of protein-loss.