Keynote Message

• The term atypical Cushing’s syndrome (AHAC) has been used to describe dogs with clinical signs of hypercortisolemia in which standard screening tests for Cushing’s syndrome are within normal limits. Alterations in concentrations of adrenocortical precursor hormones, before and after ACTH stimulation, have been used to diagnose dogs with AHAC. The questions remain—what actually is AHAC and what is the best way to diagnose this condition?
• Clinical signs associated with AHAC are the same as those seen with hypercortisolemia and include PU/PD, elevations in ALP, and vacuolar hepatopathy.
• In addition, clinical signs of hypercortisolemia and AHAC frequently seen by the dermatologist include alopecia, recurrent pyoderma, and milia.
• With the exception of alopecia, clinical signs associated with AHAC are not associated with oestrogens or steroid hormone precursors. Clinical signs in some dogs with AHAC, therefore, could be due to hypercortisolemia, but current testing methods are not sensitive enough to diagnose the condition.
• A recent study showed the sum and mean cortisol concentrations over a 9-hour period in dogs with AHAC to be significantly increased when compared to control dogs but less than those of dogs diagnosed with pituitary dependent hyperadrenocorticism (PDH), supporting the hypothesis that dogs with AHAC have increased cortisol concentrations. Dogs with AHAC also had significantly larger adrenal gland measurements than control dogs, but adrenal gland size did not differ for dogs with AHAC and PDH. This suggests that AHAC may just be PDH that we cannot yet diagnose with current testing.
• Attempts to improve the diagnostic sensitivity of the LDDS test by adjusting the cut-off value or extending the sampling times have been unsuccessful.
• Currently, diagnosis of AHAC is made based on presence of increased concentrations of adrenal sex hormones pre- and post-ACTH stimulation. Because these hormones are precursors to cortisol, they can also be increased in dogs with Cushing’s syndrome and dogs with non-adrenal illness. Therefore, evaluation of adrenal sex hormones for diagnosis of AHAC is questionable.
• Recommendations for dogs with suspect AHAC based on this new research include first performing both LDDS and ACTH tests. Adrenal ultrasound should be considered to rule out an adrenal tumor, even with normal cortisol concentrations, if clinical signs suggest Cushing’s syndrome. If no adrenal tumor is detected, consider retesting in a few months. Increased adrenal sex hormones and steroid hormone intermediates post ACTH-stimulation have been documented prior to development of hypercortisolemia in at least one dog.
• Treatment should wait for definitive diagnosis of HAC. If clinical signs are severe with negative testing, treatment with trilostane or mitotane can be considered.

Key References

1.  Behrend EN, Kooistra HS, Nelson R, et al. Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus statement (small animal). J Vet Intern Med. 2013;27:1292–1304. DOI: 10.1111/jvim.12192. https://onlinelibrary.wiley.com.

2.  Fowler KM, Frank LA, Morandi F, et al. Extended low-dose dexamethasone suppression test for diagnosis of atypical Cushing’s syndrome in dogs. Domest Anim Endocrinol. 2017;60:25–30. DOI: 10.1016/j.domaniend.2017.03.002. www.sciencedirect.com/science/article.

3.  Frank LA, Henry GA, Whittemore JC, et al. Serum cortisol concentrations in dogs with pituitary-dependent hyperadrenocorticism and atypical hyperadrenocorticism. J Vet Intern Med. 2015;29:193–199. DOI: 10.1111/jvim.12500. https://onlinelibrary.wiley.com.

4.  Frank LA, Schmeitzel LP, Oliver JW. Steroidogenic response of adrenal tissues after administration of ACTH to dogs with hypercortisolemia. J Am Vet Med Assoc. 2001;218:214–216. DOI: 10.2460/javma.2001.218.214. https://avmajournals.avma.org.

5.  Monroe WE, Panciera DL, Zimmerman KL. Concentrations of noncortisol adrenal steroids in response to ACTH in dogs with adrenal-dependent hyperadrenocorticism, pituitary-dependent hyperadrenocorticism, and nonadrenal illness. J Vet Intern Med. 2012;26:945–952. DOI: 10.1111/j.1939–1676.2012.00959.x. https://onlinelibrary.wiley.com.