Could it be Addison’s?
Linda E. Luther, DVM, DACVIM (SAIM)
Small Animal Track
2012 ISVMA Annual Conference Proceeding
Many cases presented for evaluation of vague symptoms end up having
hypoadrenocorticism.
Can you spot the classic cases?
Can you spot the not-so-classic cases?
Hypoadrenocorticism, or “Addison’s” disease, results from atrophy of the adrenal cortex, and
often presents as a diagnostic challenge. Clinical signs can vary from subtle signs to acute
collapse, and the clinical course is often waxing and waning. Untreated collapsed dogs may
die, so identifying dogs affected with this disease early is optimal. Types of
hypoadrenocorticism include the ‘classic’ glucocorticoid & mineralocorticoid deficient patient,
and the more subtle, glucocorticoid deficient patient.
Clinical signs of classic hypoadrenocorticism may include vomiting, diarrhea, lethargy,
collapse, bradycardia, abdominal pain, polyuria, polydipsia, or being “just not right”.
Physical examination findings are often nonspecific. Laboratory findings in a classic case
may include hyponatremia, hyperkalemia, decreased Na/K ratio, azotemia (with or without
an inappropriate specific gravity), hypoalbuminemia, hypoglycemia, hypercalcemia,
nonregenerative anemia. The lack of a stress leukogram is common; a normal to elevated
lymphocyte count, and normal to elevated eosinophil count in a sick dog are frequent, subtle
findings. ECG findings in hyperkalemic dogs can include bradycardia, a prolonged P-R
interval, a lack of P waves, spiked T waves and wide, bizarre QRS complexes.
THE NOT-SO-CLASSIC CASE WILL OFTEN PRESENT WITH MORE SUBTLE CLINICAL SIGNS. They will
have normal electrolytes, and will often have a lack of a stress leukogram. They may also
have a low normal hematocrit or a non-regenerative anemia, a low to borderline albumin,
hypoglycemia and hypercalcemia. These cases are commonly missed. How can you
ensure that you spot these? Look at the CBC carefully. Is there a stress leukogram? Look
at the albumin level. Is it decreased or in the low normal range? Consider the history.
Consider the lack of other obvious disease, and don’t forget to IGNORE the normal
electrolytes. If there are enough consistent findings in a dog with vague symptoms, test for
hypoadrenocorticism!
Once you suspect hypoadrenocorticism, confirmation historically has been done with an
ACTH stimulation test. However, a recent study showed that if a dog had a baseline
cortisol level that was greater than 2.0 ug/dL, he was very unlikely to have
hypoadrenocorticism. If the baseline cortisol is less than 2.0 ug/dL, hypoadrenocorticism is
not ruled out, and an ACTH stimulation test should be done.
But I thought she was in renal failure…
Cases of hypoadrenocorticism can mimic acute renal failure in that clinical signs are similar,
and azotemia with an inappropriate urine specific gravity may exist. How does the astute
clinician differentiate the two? Questions to ask include: Is there a stress leukogram? Was
the resolution of severe azotemia very rapid? Did the patient act like a ‘brand-new dog’ after
just a day of fluids?
Let’s compare “Maggie”, a 7-year-old Fs Collie that presented with vomiting and lethargy, to
“Bailey”, a 12-yr-old Mn Cocker that presented in lateral recumbancy (see Table 1). Both
dogs had severe azotemia with an inappropriate urine specific gravity. “Maggie” lacked a
stress leukogram. The electrolyte findings in both dogs were suggestive of
hypoadrenocorticism, but this finding is not pathognomonic for the disease. “Maggie”
turned out to have hypoadrenocorticism. “Bailey”, did not, and he was diagnosed with renal
failure (see Table 3). Because “Maggie” had an abnormal ACTH stimulation test as well as
abnormal electrolytes, she had glucocorticoid and mineralocorticoid deficient
hypoadrenocorticism.
Therapy for “Maggie” started with intravenous fluid therapy. The hyperkalemia was treated
with the fluids, as well as intravenous sodium bicarbonate therapy (1 mEq/kg, slow IV).
Glucocorticoids were given, initially using dexamethasone sodium phosphate (0.1-2 mg/kg
IV). Chronic glucocorticoid therapy with physiologic dose of prednisone (0.1-0.2 mg/kg/day,
doubled when she was stressed) was initiated. She was also given mineralocorticoid
therapy using Percorten®-V (Desoxycorticosterone pivalate or DOCP, 2.2 mg/kg IM or SQ
q. 25 initially). Florinef ® (fludrocortisone acetate, 0.01-0.02 mg/kg/day initially), a
mineralocorticoid which also has glucocorticoid effects, could have been used instead of
Percorten®.
Could he be an Addisonian?
Some Addisonian dogs have very subtle symptoms. “Max” is a 7-yr-old Mn Labrador
retriever that presented for a blood panel to monitor carprofen therapy that was being
chronically administered to treat degenerative joint disease (see Table 2). “Max’s” blood
panel revealed a significant, nonregenerative anemia. Upon further questioning, the owner
thought that “Max” had been quieter lately. He was really not all that sick though. Besides
the anemia, the blood work showed a lack of a stress leukogram, his electrolytes were
normal, and there was no azotemia. An ACTH stimulation test was done (see Table 3), and
“Max” indeed was an Addisonian! Since “Max” had normal electrolytes, he had
glucocorticoid deficient hypoadrenocorticism, and he was not mineralocorticoid
deficient. Chronic glucocorticoid therapy with a physiologic dose of prednisone (0.1-0.2
mg/kg/day, doubled when he was stressed), was started. Mineralocorticoid therapy was not
indicated in this dog. Some glucocorticoid deficient cases eventually develop
mineralocorticoid deficiency, thus periodic monitoring of electrolytes is indicated.
In summary, hypoadrenocorticism can be a challenging disease to diagnose. Suspicion of
the disease in dogs with vague symptoms is recommended, even in dogs that have normal
electrolytes.
Disclaimer: Please verify all drug dosages before administering.
References:
Scott-Moncrieff JCR. Hypoadrenocorticism. In Ettinger SJ, Feldman EC (eds.) Textbook of
Veterinary Internal Medicine, 7th ed. Saunders Elsevier, St. Louis, 2010, 1847-1857.
Lennon EM, Boyce TE, Hutchins RG et al. Use of basal serum or plasma cortisol
concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (20002005). J Am Vet Med Assoc 2007;231:413-416.
Thompson AL, Scott-Moncrieff JC, Anderson JD. Comparison of classic
hypoadrenocorticism with glucocorticoid-deficient hypoadrenocorticism in dogs: 46 cases
(1985-2005). J Am Vet Med Assoc 2007;230:1190-1194.
Table 1.
“Maggie”
“Bailey”
White blood cells, #/μL
Neutrophils, #/μL
Lymphocytes, #/μL
Monocytes, #/μL
Eosinophils, #/μL
Platelets, # x 103/μL
BUN, mg/dL
Creatinine, mg/dL
Calcium, mg/dL
Phosphorus, mg/dL
Na, mmol/L
K, mmol/L
Cl, mmol/L
Na/K
Urine specific gravity
12,880
7,670
2,710
1,550
890
299
130
7.7
13.8
14.6
136
9.0
103
15.1
1.015
28,290
24,750
490
2,370
520
431
130
7.7
5.5
16.1
145
9.0
111
16.1
1.015
Table 2.
“Max”
Hematocrit, %
White blood cells, #/μL
Neutrophils, #/μL
Lymphocytes, #/μL
Monocytes, #/μL
Eosinophils, #/μL
Platelets, # x 103/μL
BUN, mg/dL
Creatinine, mg/dL
Albumin, mg/dL
Na, mmol/L
K, mmol/L
Cl, mmol/L
Na/K
23.6
2,500
1,840
340
110
190
325
35
1.3
1.2
152
5.5
123
27.6
Table 3.
“Maggie”
Normal
values
5,500-16,900
2,000-12,000
500-4,900
300-2,000
100-1,490
175-500
7-27
0.5-1.8
7.9-12
2.5-6.8
144-160
3.5-5.8
109-122
< 27
Normal
values
37-55
5,500-16,900
2,000-12,000
500-4,900
300-2,000
100-1,490
175-500
7-27
0.5-1.8
2.3-4
144-160
3.5-5.8
109-122
< 27
“Bailey”
“Max”
Normal
values
Pre-ACTH cortisol, ug/dL
< 0.5
8.0
< 0.5
> 2.0
Post-ACTH cortisol, ug/dL
< 0.5
N/A
< 0.5
> 8.0
* Note that “Bailey’s” baseline cortisol adequately ruled out hypoadrenocorticism.
“Maggie” and “Max” had baseline cortisol values < 2.0 ug/dL, thus an ACTH
stimulation was needed to confirm the disease.
Quiz: Hypoadrenocorticism
1. What electrolyte changes are expected in a glucocorticoid-deficient Addisonian?
E. Normal Na, normal K
2. Which describes a stress leukogram?
3. When would a baseline cortisol level rule out hypoadrenocorticism?
A. When it is > 10 ug/dL
B. When it is < 10 ug/dL
C. When it is > 2.0 ug/dL
D. When it is < 2.0 ug/dL
E. Never
4. What ECG findings may be seen with hyperkalemia? (Select all correct replies)
A. Bradycardia
B. Tachycardia
C. Spiked p waves
D. Spiked t waves
E. Wide bizarre QRS complexes
5. What is a physiologic dose of prednisone in a dog?
A. 0.1-0.2 mg/kg/day
B. 0.5-1 mg/kg/day
C. 2-4 mg/kg/day
D. 10 mg/kg/day