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**eyelostit** · 11-11-2008, 03:11 PM

Re: Pebbles necropsy report PLease help

Gee Marianne, I know how sad you must of been reading this, I felt like I was reading my husbands autopsy.

I can't really decipher it well, other than addisions, but I thought addisons came into picture after taking cushings med's.

The compression noted by pit. gland, maybe that was the pain she was having. I'm only trying to understand it also, maybe Nat will get on board or WeHope, I know you are anxious to know and I wish I could help more.

Put that report down until Nat or Wehope come aboard it only makes you sad. Put it down

**We Hope** · 11-11-2008, 03:33 PM

Re: Pebbles necropsy report PLease help

Marianne,

Am sure you know what the macroadenoma is. Am going to start with the rest--our source will be Dorland's Medical Dictionary.

http://www.mercksource.com/pp/us/cns...md-a-b-000.htm

"Recently diagnosed w/ iatrogenic Addison�s disease."

"iatrogenic (i-at″ro-jen�ik) resulting from the activity of a health care provider or institution; said of any adverse condition in a patient resulting from treatment by a physician, nurse, or allied health professional."

The use of this term would be referring to Pebbles' need to use Trilostane for her Cushing's. As you've seen with Lysodren (mitotane) treatment, Trilostane treatment can also result in the patient going from Cushing's to a lack of enough cortisol--Addison's disease.

http://www.gcvs.com/internists/cushings.htm

"In rare cases, it is possible to permanently destroy the adrenal glands with Mitotane and these pets will require therapy with medications to replace the cortisol and other steroid hormones normally produced by the adrenal glands. Some veterinarians may choose to give low doses of cortisone with the Mitotane in attempt to prevent these clinical signs from developing. Some veterinarians may also choose to treat their patients to the extent that the adrenal gland is destroyed, creating Addison�s disease."

No one intended to create Addison's for Pebbles. Just as there are times when using Lysodren can result in Addison's, the same is so for using Trilostane. At one time, it was thought that this couldn't happen with the use of Trilostane, but it can have the same effect as Lysodren re: possibility of going from Cushing's to Addison's.

http://www.noahcompendium.co.uk/Dech...es/-36949.html

NOAH (National Office of Animal Health--UK) compendium
Vetoryl (trilostane)

"Signs associated with iatrogenic hypoadrenocorticism, including weakness, lethargy, anorexia, vomiting and diarrhoea may occur."

Anorexia is unwillingness to eat. People with a mental condition called anorexia nervosa can become so unwilling to eat because they fear gaining weight, they are honestly capable of starving. Sometimes it's necessary to give medications that have temporary anorexia as one of the side effects.

Thrombotic comes from thrombus:

"thrombus--a stationary blood clot along the wall of a blood vessel, frequently causing vascular obstruction."

"vascular--pertaining to blood vessels"

So this would be a clot in a blood vessel that could cause a problem with the blood flowing through properly.

"Changes described in pancreas, liver, gallbladder and costochondral junctions, are common age-related findings in dogs."

"costochondral--pertaining to a rib and its cartilage."

What they are saying is that the changes in Pebbles' pancreas, liver, gallbladder and ribcage areas they saw are normal for dogs her age.

Have no idea why the SNAP test indicated pancreatitis but there's no evidence of it. This was surely a false positive, but I don't know what may have triggered it. Since this test was developed at Texas A & M, I'd believe they are very interested in trying to understand this.

"The fracture of the medial coronoid processes is an incidental finding."

"medial--pertaining to or situated toward the midline."

"coronoid--shaped like a crow's beak. shaped like a crown."

"process--a prominence or projection, as from a bone."

This sounds like there was a bone fracture but it wasn't considered serious enough to be the cause of Pebbles' illness. Don't know if it was an old fracture or a new one.

"Histopathology of selected tissues is pending."

pathologic histology--the science of diseased tissues.

"Pituitary gland adenoma with thalamic compression."

"thalamus--either of two large round structures, the dorsal thalamus or simply thalamus and the subthalamus or ventral thalamus. It is composed of gray matter and located at the base of the cerebrum. It functions as a relay station in which sensory pathways from the spinal cord and brainstem form synapses on their way to the cerebral cortex. Specific locations in the thalamus are related to specific areas on the body surface and in the cerebral cortex. A sensory impulse from the body surface travels upward to the thalamus, where it is received as a primitive sensation and then is sent on to the cerebral cortex for interpretation as to location, character, and length of time. The thalamus has numerous connections to other areas of the brain as well, and these are thought to be important in the integration of cerebral, cerebellar, and brainstem activity."

http://en.wikipedia.org/wiki/Thalamus

Here you see how deep in the brain the thalamus is.

"Many different functions are linked to the system to which thalamic parts belong. This is at first the case for sensory systems (which excepts the olfactory function--sense of smell) auditory (hearing), somatic (touch), visceral (GI--gastrointenstinal system), gustatory (taste) and visual (sight)systems where localised lesions provoke particular sensory deficits."

The pituitary tumor was pressing hard on the thalamus that controls sight, sound, taste, touch and deals with the GI tract. Seeing this makes me understand why Pebbles began not wanting to eat and how it came to be that she was having the circling, etc.

I know you want to know desperately, so I'll post this portion now and continue to post portions until we've gotten to all the medical words.

Kathy

**rhodesian46** · 11-11-2008, 04:12 PM

Re: Pebbles necropsy report PLease help

Are they saying that Pebbles had a fracture on both her front elbows? If so that is impossible I had Pebbles since she was born Never once was she injured or had problems in her front legs That is weird. I wonder how this happened? Wouldn't I have noticed her limping or in pain?

ALso Pebbles had had her Stim test a month prior to her death That is when it was non stimulatory. We stopped trilo for a week and started on a lower dosage. So she went Addisonian pretty quick I wonder if all these other diseases had an effect on the change in dosage and Addison?

**We Hope** · 11-11-2008, 04:29 PM

Re: Pebbles necropsy report PLease help

"INTEGUMENTARY (skin) AND SPECIAL SENSES: Shaved areas include a 7cm and a 5cm circumferential band proximal to the right
and left elbow, respectively. The hair coat over the lateral aspect of the thorax and abdomen has diffuse patchy alopecia
(endocrine alopecia). "

alopecia--loss of hair

The lack of hair is considered due to Pebbles' endocrine problems, and you were aware of that being the reason for her lack of it in some areas of her body. I believe the shaved areas they note were done at the hospital to allow them to either conduct tests or possibly to give fluids either sub-Q (under the skin) or perhaps even intervenously.

"RESPIRATORY: A 1 x 2.5cm, well demarcated white area, is on the pleural (of the lung) surface of the middle lobe of the right lung and
does not extend into the underlying parenchyma (focal pleural fibrosis)."

"parenchyma--the essential or functional elements of an organ, as distinguished from its framework."

"focal--pertaining to or having a focus."

"pleural fibrosis-fibrosis of the visceral pleura so that part or all of a lung becomes covered with a plaque or a thick layer of nonexpansible fibrous tissue."

It sounds like this was confined to the area indicated and did not extend into the "working" portion of the lung.

"URINARY (Right kidney: 58g; left kidney: 62g): Three, slightly depressed, irregularly marginated areas ranging from 3 x 2mm
to 4 x 7mm are scattered on the surface of the cortex of the left kidney (scarring retraction)."

"margination--accumulation and adhesion of leukocytes to the epithelial cells of blood vessel walls at the site of injury in the early stages of inflammation."

"cortex--Latin word meaning bark. In anatomy, it is used for the outer layer of an organ or other structure."

"retraction--the act of drawing back, or condition of being drawn back."

So there was some inflammation seen on the outer surface of Pebbles' left kidney. I don't quite know how to interpret "scarring retraction" in this sense.

"LIVER AND PANCREAS (Liver: 1.4kg): White, moderately firm nodules, 1 to 2mm diameter, are scattered throughout the
pancreatic parenchyma (multiple adenomas/nodular hyperplasia).

The liver is mildly enlarged with a mild enhancement of the
lobular pattern (hepatocellular vacuolar degeneration, presumed). A 3cm diameter, tan, raised, moderately firm nodule is on
the visceral aspect of the distal portion of the left lateral liver lobe. On cut surface, the nodule blends into and resembles
the liver parenchyma (hepatoma/nodular hyperplasia). Similar nodules, approximately 0.6cm diameter, are scattered
throughout the liver parenchyma.

The mucosal surface of the gallbladder has three, 2 to 3mm diameter, multinodular,
exophytic proliferations (cystic mucoid biliary hyperplasia)."

"parenchyma--the essential or functional elements of an organ, as distinguished from its framework."

"adenoma--a benign epithelial tumor"

"epithelial--from epithelium--the cellular covering of internal and external surfaces of the body, including the lining of vessels and other small cavities."

"hyperplasia--abnormal increase in volume of a tissue or organ caused by the formation and growth of new normal cells."

So Pebbles' pancreas had these non-cancerous node-like growths.

hepatocellular--liver cell

"vacuolar degeneration--the formation of vacuoles in the cells of a tissue."

"vacuole--a space or cavity in the protoplasm of a cell."

This seems to say that they were of the belief that Pebbles' may have had the beginning of liver problems. And the same, non-cancerous node-like growths similar to what was found on the pancreas was also found on the liver.

"mucosa--mucous membrane. It is short for the Latin phrase tunica mucosa. adj., muco�sal., adj."

"exophytic--growing outward"

"biliary--pertaining to bile, to bile ducts, or to the gallbladder."

"hyperplasia--abnormal increase in volume of a tissue or organ caused by the formation and growth of new normal cells."

They found some node-like growths on Pebbles' gallbladder also and this appears to be their description of them. They also weren't cancerous.

"DIGESTIVE: A moderate amount of tan, roughened, gritty plaque covers the upper and lower premolar and molar teeth and
the related gingiva (gums) is diffusely reddened (dental tartar with mild periodontal disease)."

Pebbles had a bit of gum disease.

I'll continue in a bit.

**rhodesian46** · 11-11-2008, 04:40 PM

Re: Pebbles necropsy report PLease help

Here is Pebbles discharge summary Just got this via e mail

Texas A&M University

Small Animal Internal Medicine
Discharge Summary

Owner:
Marianne Halpin

Austin, TX 78748

Patient: Pebbles

Case #: 176938
Admission Date: 10/20/2008

Senior Clinician: Katherine D Snyder, DVM

Attending Clinician: Rebecca Quinn, DVM

Student: Jana McDonald
Pebbles was admitted to the Texas A&M University Veterinary Medical Teaching Hospital on 10/20/2008 .

Presenting complaint: not doing well, vomiting water

History:
Pebbles was a 10 year old, spayed female Siberian husky.
She presented to Texas A&M Small Animal Emergency on 10/20/08 for evaluation of a poor appetite and several episodes of vomiting. Mrs. Halpin had also noted increased vocalization and possible pain localized to either the abdomen or left pelvic limb. On the ride to the hospital Pebbles appeared very anxious and continued to vocalize despite attempts to soothe her.

She had a history of controlled diabetes mellitus, iatrogenic Addison's Disease, hypothyroidism, as well as a resolved episode of pancreatitis. Pebbles was on Soloxine 0.5mg BID, milk thistle 350mg BID, Trilostane 45mg SID, NPH 38U SQ BID, and fish oil 2000u BID. Mrs. Halpin also had Tramadol and Metoclopramide available to be given for pain or nausea from previous episodes of pancreatitis.

Physical Examination: Temperature - 102.0 F, heart rate - 96 beats per minute, respiration - 32 breaths per minute. Body weight - 24.0 kg, Pebbles had a body condition score of 2/5. Mentation was very vocal and anxious. On auscultation of the thorax, the lungs sounded clear, the heart sounds were normal and rhythmic. Femoral pulses were strong and normal. The eyes had no discharge but a 2mm in length lesion was seen on the center portion of her cornea. There is no discharge seen from the nose. It had been noticed that she would shake her ears and keep her head tilted to the right side. Looking down in the canal with an otoscope revealed no exudate. Pebbles� teeth had severe tarter. All lymph nodes palpated appeared to be normal. On palpation of her abdomen, she felt tense. Urination wa normal and no stools were produced. No vomiting, coughing, or sneezing was ever observed in the clinic. Neurological exam demonstrated occassional circling and an alert attitude with inappropriate responses. No other abnormalities were seen on physical exam.

Diagnostic Tests & Results:
Cortisol
Test Result Reference Unit
Cortisol, baseline 0.9 1 - 6 ug/dl
Interpretation: Continued Iatrogenic Addison's Disease

Nova
No significant findings

Snap cPLI
Positive

In-Hosptial Treatment:
� 10/20/2008 - Pebbles was started on Normosol R intravenous fluids at a rate of 130 ml/h. She was continued on Soloxine 0.5mg BID PO. Trilostane was withheld. Buprenorphine 0.3 mg intravenously q8h, Famotidine 11mg IV q12h, and Ondansetron 4.6mg IV q8h was started. She was also given a one time dose of Acepromezine.
� 10/21/2008 - Continued on Normosol R IV fluids at a rate of 130ml/h, Soloxine 0.5mg BID PO, Trilostane 45mg PO is on hold, Buprenorphine 0.3mg IV q8hrs, Ondansetron 4.6mg IV changed from q8h to q24h after the noon treatment, Famotidine was stopped when the last of the bottle was used, Novulin N 38 units withheld due to anorexia. Blood glucose monitoring was begun at 6p using the #4 Alpha track. Dosing of Novulin N was changed to BG levels >280 give 38 units, 250-279 give 30 units, 200-249 give 25 units, and below 200 do not give insulin. Boiled chicken was offered.
� 10/22/2008 - Continued on Normosol R IV fluids at a rate of 130ml/h, Soloxine 0.5mg BID PO, Trilostane 45mg PO withheld, Buprenorphine 0.3mg IV increased to q6hrs, Odansetron 4.6mg IV.

To the Owner

Diagnosis:
1. Pituitary macroadenoma with secondary neurological defecits
2. Iatrogenic Addison's Disease
3. Diabetes mellitus
4. Historical pancreatitis

Pebbles' unusual vocalization and anxiety, in combination with her pituitary dependent (PD) Cushing's Disease, lead to the suspicion of a space-occupying pituitary tumor. As we discussed, patients with PD Cushing's Disease may have a microadenoma (a small pituitary tumor) or a macroadenoma (a large pituitary tumor). Pebbles' initial autopsy report suggested a macroadenoma. The tumor was large enough that it was compressing other parts of her brain. Based on the anatomy of the brain, Pebbles' clinical signs were likely neurological abnomalities associated with brain compression. We do not believe that her abnormalities were associated with pain.

Addison's disease occurs when the body does not produce enough cortisol. This can happen as a result of Cushing's Disease therapy. This only occurs in about 5% of the animals and is usually irreversible. Other more common side effects of Trilostane include anorexia, vomiting, diarrhea, weakness. Sometimes these signs can be treated by lowering the dosage of Trilostane so that the adrenal glands produce more cortisol. Some patients require steroid therapy, and never receive Trilostane again.

We are still waiting for Pebbles' final necropsy findings, and will call you with those as soon as we receive them. The private crematorium company, Live Oaks, will get in touch with you directly concerning Pebbles' ashes.

Please rest assured that you gave Pebbles a warm and loving home and did what was best for her situation. She will not be forgotten. Thank you for entrusting us with her care.

****IF YOU HAVE ANY QUESTIONS OR PROBLEMS,
PLEASE DO NOT HESITATE TO CALL � (979) 845-2351***

_____________________________ _____________________________
Rebecca Quinn, DVM
Clinician Jana McDonald
Student

**We Hope** · 11-11-2008, 04:41 PM

Re: Pebbles necropsy report PLease help

Originally posted by rhodesian46 View Post

Are they saying that Pebbles had a fracture on both her front elbows? If so that is impossible I had Pebbles since she was born Never once was she injured or had problems in her front legs That is weird. I wonder how this happened? Wouldn't I have noticed her limping or in pain?

ALso Pebbles had had her Stim test a month prior to her death That is when it was non stimulatory. We stopped trilo for a week and started on a lower dosage. So she went Addisonian pretty quick I wonder if all these other diseases had an effect on the change in dosage and Addison?

Marianne,

I don't know where they located the fracture. Know that Pebbles went into Addison's very quickly. I remember that it was once believed that using Trilostane couldn't result in Addison's. Here's a PubMed study from 2004 detailing how a dog who'd recently started treatment for Cushing's with triostane went into Addison's. In his case, they refer to the death of adrenal tissue--necrosis.

http://www.ncbi.nlm.nih.gov/pubmed/1...t=AbstractPlus

Journal of Small Animal Practice June 2004
Adrenal necrosis in a dog receiving trilostane for the treatment of hyperadrenocorticism

"Clinical and biochemical changes suggestive of hypoadrenocorticism were observed in a 10-year-old male neutered Staffordshire bull terrier shortly after beginning therapy with trilostane for the treatment of hyperadrenocorticism. The dog's condition was stabilised with intravenous fluids, fludrocortisone and prednisolone. An exploratory laparotomy and excisional biopsy of the left adrenal gland were performed. Histopathological analysis showed adrenal cortical necrosis with reactive inflammation and fibrosis. Trilostane is a reversible inhibitor of steroid synthesis and this complication has not been reported previously."

Kathy

Since there's both pituitary and adrenal Cushing's, with pituitary Cushing's being the malfunction of the pituitary gland that produces the "signaling" hormone which tells the adrenal glands to produce cortisol, is it possible that the tumor became large enough to in effect, "cut off" the signalling from the pituitary gland?

My thought would be that in the beginning, the pituitary tumor was the cause of the gland's "over signaling" to the adrenals to produce cortisol--thus we had pituitary Cushing's. But it would seem that if a tumor can cause "over signaling", it's also possible that it could grow large enough to cut off the signaling for cortisol almost entirely or all together.

When the pituitary no longer signals the adrenals to put out cortisol or to put out enough of it, that would seem to be how one could wind up with Addison's.

**k9diabetes** · 11-11-2008, 10:29 PM

Re: Pebbles necropsy report PLease help

Regarding the fracture: http://www.vetinfo4dogs.com/delbdysp.html

I see mixed reports on all of the techniques for repairing fractured medial coronoid processes and other lesions associated with elbow dysplasia.

It looks like this fracture may be essentially the same thing as elbow displasia or a consequence of it.

Otherwise, it looks like Pebbles suffered basically almost entirely from the macrotumor on the pituitary and the compression on the brain, which was destroying cells in its vicinity.

NECROPSY REQUEST
CLINICAL DIAGNOSIS:
None.
GROSS DIAGNOSIS:
Pituitary gland adenoma with thalamic compression.
SYSTEM FINDINGS:
NERVOUS (Brain: 88g): A tan, multinodular, mottled dark red/yellow, approximately 1.5 x 0.8 cm extension from the pituitary
from the sella turcica with a slightly right lateral orientation (pituitary gland adenoma). The overlying brain parenchyma appears slightly depressed (brain atrophy secondary to the compressive neoplasm).
NECROPSY HISTOPATHOLOGY REPORT
MICROSCOPIC LESIONS:
Pituitary gland: Adenoma of the pars intermedia with acute, massive coagulative necrosis (ischemia presumed).
Brain (thalamic region overlying the pituitary tumor): Moderate, subacute, locally extensive necrosis with multifocal hemorrhage and focal lymphohistiocytic encephalitis.
INTERPRETIVE DIAGNOSIS:
Pituitary gland adenoma.
INTERPRETIVE SUMMARY:
Histopathology confirms the gross diagnosis of pituitary gland adenoma with thalamic compression. Bilateral adrenal hyperplasia is associated with the pituitary neoplasm. The compression necrosis of the thalamic region overlying the pituitary tumor that could eventually explain the neurologic signs.

Necrosis means the brain tissue that was being compressed was dying and I believe encephalitis is just another way of saying a severe inflammatory process.

Everything else appears to be either mild or benign. All of which matches her symptoms. It could be that the Trilostane caused the low cortisol or it could be the brain tumor as I've seen a couple of other dogs with brain tumors who, not being diabetic or cushinoid, experienced hypoglycemia as a result of their tumors.

Natalie

**rhodesian46** · 11-12-2008, 10:16 AM

To Better understand the necropsy by DR Bostrom

I just received a e mail from Dr B explaining some of the pancreatitis issues and fractures Hope this helps someone. Dr Bostrom says
"She had fractured coronoid processes. Those are small pieces of bone
found in the elbow joint. Fractured coronoid processes are a very
common causes of chronic arthritis in dogs. It is not a traumatic event
necessarily it is just a chronic arthritic change. The snap cPLI test
that they ran was a screening test, meaning it is a good test to rule
out pancreatitis. Once we get a positive result on that test we often
follow up with a quantitative cPLI that we send out to a laboratory. We
did not do this for Pebbles. Also she had no visible changes grossly
(with the pathologist's eyes) in her pancreas, that does not rule out
microscopic changes as the pathologist usually looks at only one section
of pancreas. There can be pockets of inflammation that they may have
missed that were evident only microscopically. Regardless whether the
pancreatitis was present or not was not clinically important at this
juncture since we are fairly certain her main concern was neurological.
Anyways I hope this helps. Don't hesitate to contact me with any
further questions.
Sincerely,
Brier Bostrom, DVM

**Cara's Mom** · 11-12-2008, 11:41 AM

Re: Pebbles necropsy report for input

Marianne, I know this must be hard on you and I am so sorry. However, posting this info is very informative to the rest of us and I like to thank you for sharing with us.
Hope things will be better soon.
Hugs,

**rhodesian46** · 11-12-2008, 04:41 PM

Re: Pebbles necropsy report for input

Thanks Marion,
I hope that I have helped someone here. It is hard to post this stuff You are right. I know that I did the right thing for Pebbles I am at peace with my decision It is just hard to read as it is so graphic even though I didn't know what it meant. I fought so damn hard to keep her alive and she fought so hard to stay with me. I am glad that I got to spend all that quality time with her even though I worried about her. It is now time to spend with my other dogs as they deserve my attention. Pebbles has a sister Jasmine Will post pics of her and the clan. My husband has offered to get me another Husky I don't think that is fair to my geriatric dogs and cats Out of my 5 dogs 3 are over 7 years old. The boys are less than 3.. Thanks everyone for your patience and understanding
Marianne and Angel Pebbles

**CarolW** · 11-12-2008, 09:55 PM

Re: Pebbles necropsy report for input

Marianne - yes; you are doing a HUGE service to everyone, as you've been doing from the very start of your thread. I know it's hard to do. I've read the entire thread here, as well as on the Cushings board. I personally thank you for updating us. Thanking Kathy and Natalie, too.

Wed, 12 Nov 2008 20:55:10 (PST)

**eyelostit** · 11-12-2008, 11:49 PM

Re: Pebbles necropsy report for input

Marianne thanks also for posting those reports, it helped me alot understanding what was happening with Chief body and his cushings the past 2 yrs, I've had other older dogs with arthritus, but with him it was a little more than that, i could just tell from the experience with my other older doggies. I'd bet Chief had alot of what was in that report.

You really took care of your baby Pebbles, and even taking the time to post all the information so you could understand all of it had to be so hard on you. You've helped us all.

Take time now to heal, your other doggies will help you they got Pebbles spirit in them and they know they have a great mom.

**k9diabetes** · 11-13-2008, 11:03 AM

Re: Pebbles necropsy report for input

Inflammation definitely has much to do with the neurological symptoms. Dr. Khuly's dog, Sophie, had radiation treatment for her brain tumor but first they reduced the inflammation from the tumor.

Sophie is one of the dogs I mentioned who was experiencing low blood sugar, which eventually pointed them to her tumor when the symptoms started to show up as neurological effects rather than as an insulinoma.

I am not sure how to find the archived posts on Sophie as Dr. Khuly's blog is undergoing an upgrade, but here's a link to her site, which is a great one: http://dolittler.com/. And I did find one post on Sophie: http://dolittler.com/2008/08/26/dog....radiation.html.

Natalie

**rhodesian46** · 11-13-2008, 03:48 PM

Re: Pebbles necropsy report for input

Natalie,
That is a lot of radiation and alot of anesthesia My god. ANd the tumor will grow back again. Poor dog I wonder if the radiation is a consideration if the tumor is not as large as Pebbles and not as many neurological problems Natalie please check out the cushings site There is a blue heeler with nosebleeds that has just been dx with cushings. No tests are posted yet I thought of Chief on the nosebleeds.
MArianne

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