Could it be Addison’s?
Linda E. Luther, DVM
Diplomate ACVIM (SAIM)
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.
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, they were 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), 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 chronically administered to treat degenerative joint disease (see Table 2).
“Max’s” blood panel revealed significant anemia. Upon further questioning, the owner thought that he had been quieter lately. He really was 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 was 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.
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 (2000-2005). 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.
|White blood cells, #/μL||12,880||28,290||5,500-16,900|
|Platelets, # x 103/μL||299||431||175-500|
|Urine specific gravity||1.015||1.015|
|Table 2.||“Max”||Normal values|
|White blood cells, #/μL||2,500||5,500-16,900|
|Platelets, # x 103/μL||325||175-500|
|Table 3.||“Maggie”||“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 rule in the disease.|
There are ulcerated lesions starting on ear margins, later involving lip margins and periocular area as well as neck. Pruritus started after ulcerated lesions appeared. Skin scraping – neg., DTM – neg., Cytology – PMN’s and bacteria, C&S – pending, Dermohistopathology – pending, Bloodwork – normal. She is an outside cat, in a multicat household with no other pets involved. There are no external parasites, owner is not pruritic, no change in diet, on commercial pet food. Gave depo-medrol injection 10 days prior to biopsy. Expect biopsy results in 7 days.
This consultation is based on our phone consultation, submitted history and clinical photos. Thank you for the clinical photos which were helpful. I agree with your suspicion that immune-mediated disease is most likely. Differential diagnoses would include: Erythema multiforme (drug-induced, paraneoplastic, idiopathic) and pemphigus foliaceus (drug-induced, paraneoplastic are possible causes). Lupus erythematosus less commonly occurs in cats so is considered less likely. A cutaneous drug reaction also appears less likely in this case given the cat’s lack of drug history (no medications were being administered prior to the onset of skin disease). Although severe allergic dermatitis can sometimes mimic immune-mediated disease in the cat, the severity of the clinical presentation also makes this less likely. I would also make sure to closely examine mucosal surfaces (perianal, oral)- mucosal surfaces are involved it could indicate vesicular auto-immune disease (pemphigus vulgaris, Stevens-Johnson Syndrome, epidermolysis bullosa acquisita). Immunosuppressive therapy will likely be required to control this disease process. Pending skin biopsies, I would recommend starting this cat on immunosuppressive doses of glucocorticoids (typically 2-3 mg/kg of Prednisolone [over prednisone] divided BID). I start to taper after there has been 75-80% improvement (often within 2 weeks). New lesions should not be developing & older lesions regressing. I would not recommend adding in an additional immunomodulatory agent at this time until after the biopsy results have been reviewed.
Additional follow-up is requested on this case: biopsy report, response to initial therapeutic recommendations, etc. Addendum comments and additional therapeutic recommendations can be made at that time.
Per our phone conversation, the dermatopathology report is consistent with feline pemphigus foliaceus. Pemphigus foliaceus (PF) is a cutaneous auto-immune disease which most commonly occurs in middle aged to older cats. Another consideration would be paraneoplastic pemphigus; I would be suspicious of this if the skin lesions are not responding to appropriate therapy (this is typically more difficult to treat). Treatment for PF is often life-long, however some cats will go into extended periods of remission (without maintenance medications). Immunosuppressive therapy is required to control this disease. I recommend immunosuppressive doses of glucocorticoids (typically 2.2 mg/kg of Prednisolone [over prednisone] divided BID). I start to taper after there has been 75-80% improvement (often within 2 weeks). New lesions should not be developing & older lesions regressing. I often recommend a second immunosuppressive agent to control the disease and allow for lower doses of glucocorticoids to be used. Options include Chlorambucil or Atopica (Cyclosporine). Most commonly chlorambucil (0.1-0.2 mg/kg qd-qod) is used; tapered further over time. Monitor for myelosuppression. Obtain a baseline CBC, Chemistry profile & UA prior to initiating therapy. Recheck CBC values every 2 weeks for the first 6-8 weeks; then every 3-6 months. Although PF is often responsive to therapy, it can be a difficult auto-immune disease to manage. If remission is not initially achievable, I recommend referral to a veterinary dermatologist if possible.
Please contact me if this report is inconsistent with your clinical findings or you have additional questions. Please contact me at PetRays phone number listed below.
Terri Bonenberger, DVM
Diplomate, American College Veterinary Dermatology
3 week Update
The ulcerated lesions have healed and scabs have fallen off. The cat is doing very well.