Q & A: Can Basal Cortisol Value Be Used To Diagnose Addison's Disease?

My patient is a 2-year-old MN German short-haired pointer, a 1-day history of lethargy, anorexia, and vomiting once. On physical examination, he was quiet but alert and had good color and a normal heart rate.

Here are an overview of the dog's laboratory results:

• Complete blood count revealed mild lymphocyosis and eosinophilia.
• Serum urea nitrogen and creatinine were both normal.
• Serum sodium was normal at 140 mEq/L.
• Potassium was high at 6.2 mEq/L.
• The Na:K ratio was low at 22.5.
• A basal cortisol concentration was 1.9 μg/dl (reference range, 1-4 μg/dl).

Two questions:

1. Can I make a diagnosis of Addison's disease based upon this dogs' clinical signs, and bloodwork (i.e., lymphocyosis and eosinophilia, hyperkalemia, and low Na:K ratio)? Is the basal cortisol concentration low enough to confirm the diagnosis or do I need to do an ACTH stimulation test? I've heard that you can exclude Addison's disease if the basal cortisol is higher than 2.0 μg/dl, so I'm hoping that the 1.9 μg/dl cortisol value is low enough to confirm the diagnosis.
2. If a single 0.5 mg/kg dose of prednisone was given to this dog, how long would I have wait to do an ACTH stimulation test?

My Response:

You definitely need to do an ACTH stimulation test to confirm Addison's disease in this dog.

First of all, although the routine blood work is certainly suspicious, there are a number of canine conditions other than Addison's disease that can lead to lymphocyosis or eosinophilia, as well as a low sodium to potassium ratio (1).

A 2007 study reported that almost all dogs with Addison's will have serum or plasma cortisol values less than 2 μg/dl and proposed that the use of a basal cortisol determination can be used as a screening test to rule out hypoadrenocorticism (2). Basically, Addison's disease can be excluded in any dog that has a baseline cortisol >2 μg/dl.  However, if the baseline cortisol concentrations <2.0 μg/dl, little to no information regarding adrenal gland function can be obtained and an ACTH stimulation test MUST be done to make a definitive diagnosis.

The bottom line: dogs with Addison's will generally have very low to undetectable serum cortisol concentrations (<1.0 μg/dl). A few dogs with maintain low-normal serum cortisol concentrations, between 1.0-2.0 μg/dl (2,3).  Although sick dogs without Addison's disease rarely have low cortisol concentrations, low-normal cortisol values (between 1.0-2.0 μg/dl) are common in sick dogs without adrenal gland disease.

In answer to your second question, waiting 48 hours after administration of a single dose of prednisone will be long enough to do the stimulation test.

If the dog is symptomatic and you are worried about adrenal crisis, it would be fine to give a small dose of dexamethasone (1-2 mg) or give a routine monthly dose of Percorten (2.2 mg/dl). Neither will cross-react in the cortisol assay to falsely elevate the measured values.

However, all of forms of glucocorticoid therapy and well as fludrocortisone acetate (Florinef) will cross-react in the cortisol assay and should not be given before the ACTH stimulation test is completed.

References:

1. Nielsen L, Bell R, Zoia A, et al. Low ratios of sodium to potassium in the serum of 238 dogs. Vet Rec 2008;162:431-435.
2. Lennon EM, Boyle 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.
3. Peterson ME, Kintzer PP, Kass PH. Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism: 225 cases (1979-1993). J Am Vet Med Assoc. 1996; 208:85-91