Current concepts in canine adrenal disease (Proceedings)
ACTH stimulation test
Unfortunately, the cost of cosyntropin, the most reliable agent with which to perform an ACTH stimulation test, is expensive. When cosyntropin was a fraction of its current cost, the dosing for an ACTH stimulation test was simple: one 250-µg vial per dog. A dose of 5 µg/kg IV or IM has been established as resulting in equivalent results (Kerl ME, et al. JAVMA 1999;214:1497-1501, Behrend EN, et al. JAVMA 2006;229:528-530). Once reconstituted, however, cosyntropin is not stable and must be frozen to maintain potency. For freezing and storage, it should be reconstituted with 1-ml sterile saline, aliquoted into 50 µg doses (0.2 ml) in TB or insulin syringes and frozen at -20C. At anything warmer, it is likely only stable for 21 days and should be stable for up to 6 months at -20C in a dedicated freezer (one that is not constantly opened and closed). Unexpected ACTH stimulation test results should prompt the user to question the potency of stored cosyntropin.Desmopressin stimulation test
The DST is intended to be used as a differentiation test for pituitary-dependent hyperadrenocorticism and adrenal tumor. DDAVP stimulates V3 receptors in the pituitary, specifically expressed in pituitary corticotropes. In pituitary corticotrope tumors, this receptor is over-expressed. Stimulation of the V3 receptor results in marked ACTH release and subsequent marked increase in cortisol, a response that would not be seen with adrenal tumors. In one study, 80 dogs suspected of having Cushing's disease were evaluated with this test (27 non-adrenal disease, 46 PDH, 7 AT). The peak cortisol rise occurred at 30 minutes and increased by a median of 51% in dogs with PDH (range -24 to +563%). Dogs with AT had a change in baseline cortisol of -12% (range -44 to +5%). Using a %rise cut-off of 10%, the test had an 87% sensitivity for identifying PDH with 100% specificity. If the 20% cut-off was used, the sensitivity dropped to 76%. As a comparison, both abdominal US and the endogenous ACTH test had a sensitivity of 84% for differentiating disease (although the abdominal US probably more accurately had a sensitivity of 100% in this study, as they used enlarged adrenals as a marker, not just symmetrical adrenals).
Atypical hyperadrenocorticism in dogs: 17a-OH-progesterone
The diagnosis of hyperadrenocorticism is usually straight-forward, however a few dogs will have equivocal testing on the ACTH stimulation test or low-dose dexamethasone suppression test. In one study of 40 dogs with PDH and 12 with AT, the ACTH stimulation test was accurate in 79%, the LDDS in 93%. The measurement of 17a-OH-progesterone was only abnormal in 69% of these dogs, but was abnormal in 2 dogs that had normal cortisol but other findings suggestive of hyperadrenocorticism. The suggestion in the literature is that some dogs may have defects in the pathway of conversion of cholesterol to cortisol, resulting in excess production of intermediate metabolites, such as 17a-OH-progesterone. In most cases of Cushing's disease, these levels are proportionate with cortisol, even after the ACTH stimulation test, but in a small number of cases, the cortisol levels may not be diagnostic of Cushing's disease
Author note: Although uncommon, we have recognized a few cases of atypical hyperadrenocorticism. We do not routinely run a sex hormone profile with every dog, but currently recommend drawing an extra serum sample with the pre- and post-ACTH samples. This extra serum sample can be frozen and submitted at a later date for 17a-OH-progesterone or other sex hormone assays if needed. Drawing the sample with the original ACTH stimulation test saves the client the expense of cosyntropin a second time. Melatonin is often suggested as therapy for dogs with adrenal sex hormone excess, but there is no evidence that it reduces levels of these hormones, even if haircoat changes (alopecia X) resolves in some of these dogs.