Zycortal Symposium Proceedings

Confirming the diagnosis of Addison’s Disease and how to avoid pitfalls in diagnostic workup

Patty Lathan, VMD, MS, DACVIM

ACTH Stimulation Tests

Despite attempts to identify alternative diagnostics, the gold standard for definitive diagnosis of hypoadrenocorticism is still the ACTH stimulation test. A baseline cortisol sample should be collected, then a dose of 5 μg/kg, up to 250 μg/dog, of tetracosactide (Synacthen ® ) is given intravenously (intramuscular is not recommended due to questionable absorption in dehydrated and/or hypovolemic patients). One hour post-stimulation cortisol samples of <2 µg/dl (55 nmol/l) are consistent with hypoadrenocorticism. Rarely, cases of secondary hypoadrenocorticism with low ACTH concentrations may have post-stimulation cortisol values up to 3 μg/dl (Peterson et al, JAVMA, 1996). Some clinicians have questioned whether one hour post-ACTH cortisol concentrations above 2 μg/dl, but below the laboratory’s reference range, may represent a subset of dogs with hypoadrenocorticism. Wakayama et al (Vet Record, 2017) evaluated nine dogs with suspected atypical hypoadrenocorticism that had post-ACTH cortisol concentrations ranging between 3.4 and 8.0 μg/dl (94 and 223 nmol/l). In the seven dogs for which follow-up was available, four dogs were eventually diagnosed with inflammatory bowel disease, two dogs had no return of clinical signs following discontinuation of prednisone, and one dog did not respond to glucocorticoid treatment. Thus, this study does not provide evidence for the diagnosis of hypoadrenocorticism in dogs with post-ACTH cortisol concentrations >3 μg/dl (84 nmol/l). Any glucocorticoids given days prior to the test may blunt the response, and it is not uncommon for a dog with a history of recent glucocorticoid administration to have a post- stimulation cortisol of 2.5–5.0 µg/dl. Even aural glucocorticoids can suppress the axis and result in post-ACTH cortisol concentrations as low as 2 μg/dl (Aniya et al, Vet Derm, 2008). Most synthetic glucocorticoids (including prednisone and methylprednisolone) will interfere with the cortisol assay itself, and may cause a falsely increased cortisol result. However, dexamethasone and triamcinolone do not cross-react with the cortisol assay, and may be given prior to or during the ACTH stimulation test.

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