HYPOADRENOCORTICISM
The Great Pretender
Sarra Borne UID: 000493586
VETE 405: Pharmacology and Pharmacy
Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
Finnegan is a 9 year-old, normally 77- 79 lb, MN, Labradoodle who was initially referred
to the internal medicine department of Veterinary Specialists of North Texas (VSNT) for
increased renal values, and hyperphosphatemia. Finnegan was originally from the Washington
D.C. area, and had only moved to Texas recently. Shortly after his arrival in the Dallas area, he
had an episode of hind end collapse while going upstairs. This was his first such episode. His
owners took him to the emergency clinic where he was examined and diagnosed with lower back
pain and neuritis. At that time Finnegan was placed on Rimadyl ® (carprofen) at a dose of 75
mg PO q 24h (twice daily).
The following day October 23rd 2013, Finnegan had another episode of apparent hind end
weakness, so his owners took him to a local day practice. While there he was sedated and
radiographs of his spine, shoulders, pelvis and coxofemoral joints were done. The cervical spine
was overall normal, with no signs of degeneration or collapse. The lumbar spine, pelvis and
coxofemoral joints were all within normal limits. Radiographically his shoulders showed the
formation of osteophytes (bone spurs), and joint mice (small, loose pieces of bone in the synovial
space) bilaterally on the caudal points of the humerus and his scapular rim showed some
remodeling. He was assessed to have detectable pain in the right shoulder region, and
osteoarthritis bilaterally, with the left being greater than the right.
Osteoarthritis, also known as degenerative joint disease is a chronic degenerative disease
that affects one or more joints in the body. It is caused by a deterioration of joint cartilage.
Cartilage is a smooth, resilient tissue that lines the joints, allowing nearly frictionless joint
movement and providing shock absorption. The deterioration of cartilage leads to increased
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
friction and inflammation of the joints. This erodes the bone and can cause formation of new
bone, called osteophyte (bone spur) formation, which interferes with normal movement and can
cause pain. (Lennon & Marcellin-Little, 2005)
Figure 1: The x-ray on the left is an abnormal glenohumeral or shoulder joint. Image on the right is a normal
glenohumeral joint. (Fairfield Veterinary Centre, n.d.)
Finnegan’s owners were instructed to continue the Rimadyl ® as previously prescribed,
and to return if there was no improvement or if there was another flare up of symptoms.
On October 24th, Finnegan returned to the day practice with a complaint of vomiting,
lethargy and inappetence. Finnegan was mildly dehydrated as evidenced by a decreased skin
turgor and slightly tacky mucous membranes. His rectal temperature (T) was 99.4 and his
weight was 68 lb. At this time a complete blood count and serum chemistry panel were run. The
CBC was within normal limits other than a few changes related to dehydration, the serum
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
chemistry panel showed signs of moderate to marked azotemia, hyperphosphatemia, and a slight
increase in plasma proteins. Blood values on 10/24/2013 from the day practice
Normal Range (Heska)
103/ul
WBC
13.0
6.0 -17.0
HCT
55.7
37-55 %
RBC
8.94
5.50 – 8.50 106/ul
BUN
127.7
9 – 29 mg/dl
CREA
3.8
0.4 – 1.4 mg/dl
Phos
13.7
1.9 – 5.0 mg/dl
TP
7.9
5.5 – 7.6 g/dl
Albumin
4.0
2.5 – 4.0 g/dl
Globulin
3.9
2.0 – 3.6 g/dl
ALT
87
0 – 120 U/L
ALP
44
0 – 140 U/L
GGT
15
0 – 14 U/L
K
8.1
3.8 – 5.3 mEq/L
Na
133
141 – 152 mEq/L
Cl
108
102 – 120 mEq/L
The assessment was renal insufficiency of undetermined cause. The differential included
occult infection, leptospirosis, toxin exposure or neoplasia. At this point, Finnegan was referred
to VSNT for monitored overnight hospitalization with intravenous fluids, and an ultrasound
examination of the abdomen. The referring veterinarian was concerned that Finnegan might
3
Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
have leptospirosis. The referring veterinarian sent leptospirosis titers to a reference lab, and they
were not available at the time of his initial exam with the internists at VSNT. All seven of the
tested serovars eventually came back negative effectively eliminating infection with leptospirosis
as part of the differential.
On Finnegan’s arrival at VSNT a complete history was taken. There was no history of
toxic exposure, and no travel history other than the family move from the East Coast. The
owners noted that Finnegan is a couch potato indoor dog. The owners commented that Finnegan
had not recovered well from the anesthetic event the previous day, and was lethargic, had
vomited several times, and wouldn’t eat.
On physical examination it was noted that Finnegan was bright and alert. He had a rectal
temperature (T) of 98.6 F, heart rate (HR) 132 bpm, respiratory rate (RR) 36 bpm, and weighed
70.4 lb on our scale. The abdominal palpation elicited discomfort on palpation of the kidney
area. An abdominal ultrasound was done where it was discovered that Finnegan had a normal
left kidney, and an absent right kidney.
The radiologist had the following comments: Absent right kidney. Considerations are
given to renal agenesis (one or both fetal kidneys fail to develop) or possibly a severe renal
hypoplasia (an abnormally small kidney that has a reduced number of or smaller nephrons)
resulting in unrecognizable renal tissue. The mild pelvic renal dilation on the left could be due to
mild pyelonephritis (a urinary tract infection affecting the kidneys), renal insufficiency or fluid
therapy. Otherwise a sonographically normal abdomen. A radiographic or CT intravenous
pyelogram could be considered to evaluate the expected location of the right kidney. The
ultrasound images are of Finnegan’s left kidney, and the area where his right kidney should be.
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
5
Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
A urinalysis via cystocentesis demonstrated the following values:
Appearance
Clear
Color
Dark Yellow
Specific Gravity
1.076
Bacteria, WBC, Casts, Crystals, Epithelial None Seen
Cells
pH
6.5
RBC
Occasional
Finnegan was admitted to the hospital for aggressive fluid diuresis. He was prescribed
ampicillin at 22 mg/kg IV q 6 h to treat for the potential leptospirosis. Finnegan was maintained
in the quarantine area, and the staff was instructed to treat him as potentially infectious.
Finnegan did well overnight, and the azotemia was almost completely resolved by the
following morning.
10/25/13
6 AM
Normal (Catalyst Analyzer)
BUN 6am
33
7-27 mg/dl
CREA
1.4
0.5 – 1.8 mg/dl
Phos
4.5
2.5 – 6.8 mg/dl
TP
6.3
5.2 – 8.2 %
Globulin
3.2
2.5 – 4.5 g/dl
Albumin
3.1
2.3 – 4.0 g/dl
T. Bili
0.2
0.0 – 0.9 mg/dl
Na
143
144 – 160 mmol/L
K
7.6
3.5 – 5.8 mmol/L
Cl
114
109 – 122 mmol/L
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
The fluid rate was decreased throughout the day, and his BUN remained within normal
limits.
10/25/13
3 PM
Normal
BUN
24
7-27 mg/dl
Na
144
144 – 160 mmol/L
K
6.8
3.5 – 5.8 mmol/L
Cl
113
109 – 122 mmol/L
He was released that afternoon on oral doxycycline at 5 mg/kg q 12h, pending the
leptospirosis results. It was recommended that Finnegan be fed a low protein diet such as Hill’s
Prescription k/d or Purina Veterinary Diet NF, and that he be allowed free access to water. A
recheck was scheduled with his primary vet for the following week.
On 10/28/2013 Finnegan had another episode of collapse and was taken to the emergency
clinic. His vital signs were 71.8 lb, rectal temperature 100.5 F, heart rate 76 bpm, respiratory
rate 28 bpm. Alert. A CBC and serum chemistry were run, and the results showed a mild
azotemia, hyperphosphatemia, hyperkalemia, hyponatremia, and a mildly increased hematocrit.
10/28/2013
9:25 PM
Normal (Heska analyzer)
HCT
57.5
37 – 55%
BUN
63.1
9.0 – 29.0 mg/dl
CREA
2.2
0.4 – 1.4 ,g/dl
Phos
6.0
1.9 – 5.0 mg/dl
Na
134
3.8 – 5.3 mEq/L
K
8.5
141 – 152 mEq/L
CL
108
102 – 120 mEq/L
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
Finnegan was hospitalized overnight on intravenous fluids, and referred back to VSNT
for follow-up in the morning. A cardiac arrhythmia was noted by the emergency clinic possibly
related to the elevated potassium.
The differential diagnosis was still acute renal failure,
leptospirosis, or other renal disease.
On the morning of 10/29/13 Finnegan transferred back to VSNT for further care. His
vital signs were 70.7 lb, rectal temperature 101.3, HR 90, RR panting. His owners related the
following: “After coming home on 10/25 and sleeping for most of the day, he was steadily
improving, ate some canned dog food. The following day he was more alert and ate hungrily
and drank water, more like himself. Yesterday 10/28 Finny wanted to chase his ball, we went for
a walk and he was himself, ate and drank normally, had a normal bowel movement, on evening
walk around 8pm he would not get up so we took him next door (emergency hospital).
It was again noted that Finnegan had an irregular heartbeat, so the doctor ordered an
ECG.
The
results
were
consistent
with
hyperkalemia. Tall, peaked T-waves, shortened
QT interval, and a depressed ST segment. This
particular pattern was the result of atrial standstill
which is the lack of atrial activity resulting from a failure of atrial depolarization. The ventricles
still function normally. This can be caused by electrolyte abnormalities especially hyperkalemia
(which can develop secondary to a number of conditions including Addison’s disease, oliguric
renal failure and urethral obstruction), cardiomyopathy, muscular dystrophy and drug toxicity.
(WikiVet, 2013)
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
The atrial standstill and the hyperkalemia, and the hyponatremia, plus the faxed copy of
the negative leptospirosis titers were highly suspicious for hypoadrenocorticism or Addison’s
disease. An ACTH stimulation test was ordered. A baseline serum cortisol sample was drawn, a
dose of cosyntropin at 5mcg/kg was given IV and a post ACTH serum cortisol sample was
drawn an hour later. The results were conclusive.
PRE ACTH CORTISOL <0.2 ug/dl
POST ACTH CORTISOL <0.2 ug/dl
ACTH reference range:
<2 Post-ACTH cortisol consistent with hypoadrenocorticism.
Finnegan was again hospitalized overnight and given a loading dose of dexamethasone
sodium phosphate at 0.15 mg/kg IV, and then a second dose 12 hours later at 0.075 mg/kg IV.
He was maintained on 5% Dextrose in 0.9 % NaCl intravenous fluids, and did remarkably well
overnight. The following day he was treated with the mineralocorticoid Percorten-V ® (DOCP
or desoxycorticosterone pivalate) at 2.2 mg/kg IM, which is to be repeated every 25 days.
DOCP is a long-acting mineralocorticoid agent which is indicated for the parenteral treatment
of adrenocortical insufficiency in dogs (Plumb, 2011). That afternoon Finnegan was released
with a prescription for Prednisone 30 mg PO q 24 hr for 3 day, then 20 mg PO q 24 hr for 7 day,
then 10 mg PO q 24 hr until otherwise directed. The owners were instructed to continue the low
protein diet, and return in 10 days for a recheck examination. They were also given several
handouts on Addison’s disease.
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
We saw Finnegan back on 11/11/13 and he looked remarkable. His energy and appetite
were back. He had no further episodes of collapse, and his blood work was all within normal
limits. A recheck was scheduled for two weeks for another DOCP injection and electrolytes.
11/11/13
Normal (Catalyst)
BUN
22
7-27 mg/dl
Creat
1.3
0.5-1.8 mg/dl
Phos
3.7
2.5-6.8 mg/dl
Na
154
144-160 mmol/L
K
3.9
3.5-5.8 mmol/L
Cl
118
109-122 mmol/L
The owners had some concerns about the cost involved in the DOCP injections, as
Finnegan is a rather large dog, and DOCP is not inexpensive. The discussed it with the internist
and the decision was made to switch to fludrocortisone (Florinef ®) which is an oral
mineralocorticoid at a dose of 0.01 mg/kg q 12 hr. Finnegan’s dose came out to 0.3 mg.
Commercially available fludrocortisone is only available in 0.1 mg tablets, so his prescription
was called into a compounding pharmacy.
Fludrocortisone has some glucocorticoid activity as well as mineralocorticoid, so it may
have more side effects than DOCP. These may include polyuria, polydipsia, polyphagia,
and poor skin and coat. If Finnegan receives an overdose it could lead to hypotension,
hypernatremia, edema, and hypokalemia. Monitoring is crucial, especially during his
first few months of therapy (Brooks, 2012).
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
Finnegan returned for another follow-up visit on 11/26/2013. His owners are very
pleased with his progress. He is eating and drinking normally, has a normal activity level, and
takes his medications well. Their only complaint is that Finnegan is having some soft stool with
occasional mucus, but no blood.
His vital signs were good. T 99.1 F, HR 140, RR 50. He is back to his normal weight of
76.9 lb. An electrolyte panel was ordered and all values were within normal limits.
11/26/13
Normal (Catalyst)
Na
159
144-160 mmol/L
K
3.6
3.5-5.8 mmol/L
Cl
44
109-122 mmol/L
A rectal exam was done and it was normal. There were no parasites found on a fecal flotation. It
was suggested that the owners try adding some fiber to Finnegan’s diet, which currently consists
mostly of canned Hill’s Prescription Diet k/d. Some methods of doing this are adding green
beans, carrots and/or canned pumpkin. Also ¾ tsp. of Benefiber or Metamucil may be of benefit.
Finnegan’s next recheck is scheduled for a month. His fludrocortisone is to be refilled as
needed.
Hypoadrenocorticism or Addison’s disease is a deficiency of adrenocortical hormones
that is most commonly seen in young to middle-aged dogs. It may be familial in Standard
Poodles, so Finnegan may have inherited the genetic disposition from his Poodle ancestors.
Clinical signs of Addison’s disease are often indistinct. They may be acute or chronic, appear
episodic for weeks or even months and intensify in stressful situations
(Labor fur Klinische Diagnostik, 2009). This is one of the reasons that Addison’s disease is
known as “the great pretender”, it has the ability to mimic other common canine diseases. The
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
differential diagnosis list is long and includes primary GI disease (especially infection with
Trichuris vulpis or whipworm), renal failure, liver failure, uroabdomen, pleural effusion, acute
pancreatitis, toxin ingestion, leptospirosis, neurologic disease and many others. History, physical
exam findings, and other diagnostics should help whittle down this list.
pathognomonic
clinical
signs
for
hypoadrenocorticism
and
There are no
naturally
occurring
hypoadrenocorticism is an uncommon canine disease with estimates of its incidence ranging
from 0.36% to 0.5 % (Klein & Peterson, 2010). Naturally occurring primary adrenocortical
failure occurs from atrophy or destruction of all three adrenal cortical layers, which results in
inadequate secretion of both mineralocorticoids and glucocorticoids (Kintzer & Peterson, 1997).
Immune mediated destruction of the adrenal cortex appears to cause this form of primary
hypoadrenocorticism, and is the most common reason for primary hypoadrenocorticism in
humans (Feldman & Nelson, 2004).
Hyperkalemia, hyponatremia, hypochloremia, and decreased sodium to potassium ratios
represent the classic electrolyte changes in Addisonian dogs, and hypoadrenocorticism should be
on the differential list anytime this pattern of electrolyte imbalance is seen.
A definitive
diagnosis of Addison’s disease can be made with the ACTH stimulation test.
Dogs with
Addison’s disease do not possess adequate reserves of cortisol to adequately respond.
The prognosis is fairly good.
Finnegan will require lifelong mineralocorticoid and
glucocorticoid supplementation. His serum electrolytes will need to be monitored on a regular
basis, every few weeks until he stabilizes, and then quarterly. However, with drug therapy he
can return to being a clinically normal and healthy animal with normal blood parameters. A
study evaluating long-term treatment of 205 dogs with hypoadrenocorticism (1979-1993)
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
reported that there was a good to excellent response to treatment in more than 80% of the dogs,
and a fair response tin 12.5% (Kintzer & Peterson, 1997) The median survival time for dogs in
this study was 4.7 years and many of the dogs were still alive at the end of the study period.
There was no difference in survival time between dogs treated with fludrocortisone versus
DOCP. Of the 124 dogs that died, 120 expired for reasons unrelated to hypoadrenocorticism
(Kintzer & Peterson, 1997)
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Sarra Borne
VETE 405: Pharmacology and Pharmacy
UID: 000493586
November 30, 2013
Assignment: FINAL EXAM CASE STUDY
Hypoadrenocorticism the Great Pretender
References
Brooks, W. (2012, March 6). Fludrocortisone acetate. Retrieved from VeterinaryPartner.com:
http://www.veterinarypartner.com/Content.plx?A=536
Feldman, E., & Nelson, R. (2004). Canine and feline endocrinology and reproduction (3 ed.). St.
Louis, Missouri: WB Saunders.
Kintzer P.P., P. M. (1997, March). Primary and secondary canine hypoadrenocorticism.
Veterinary Clinics of North America Small Animal Practice, 27(2), 349-357.
Kintzer, P., & Peterson, M. (1997, Mar-Apr). Treatment and long-term follow-up of 205 dogs
with hypoadrenocorticism. Journal of Veterinary Internal Medicine, 11(2), 43-49.
Klein, S., & Peterson, M. (2010, January). Canine hypoadrenocorticism: Part 1. The Canadian
Veterinary Journal, 51(1), 63-69. Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797351/
Labor fur Klinische Diagnostik. (2009, June). Addison's disease in dogs: What do lab results tell
us. Retrieved from Laboklin Aktuell:
http://www.laboklin.de/pdf/en/aktuell/lab_akt_0906_en.pdf
Lennon, E., & Marcellin-Little, D. (2005). Canine Osteoarthritis. Retrieved from Arthritis M.D.:
http://www.arthritismd.com/canine-osteoarthritis.html
Normal Shoulder Joint. Fairfield Veterinary Centre, Leicestershire, UK. Retrieved from
http://www.fairfieldvets.co.uk/ic/dog/erin-1.htm
Plumb, D. (2011). Plumb's Veterinary Drug Handbook (Vol. 7). Ames, Iowa: Wiley-Blackwell.
WikiVet. (2013, October 15). Atrial Standstill. Retrieved from
http://en.wikivet.net/Atrial_Standstill
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