Increased ACTH secretion from the pituitary gland is the most commonly recognized cause of canine hyperadrenocorticism (HAC).
Functional adrenocortical adenomas or carcinomas that auto- nomously secrete cortisol comprise the remaining natural occurrence
of HAC in our classical understanding of this endocrinopathy.
Figure 1: Abbreviated steroid production pathway — adapted from (2) Ristic — shows those steroid hormones evaluated by the
adrenal panel profile. Note: Trilostane inhibits those pathways involving 3B hydroxysteroid dehydrogenase.
Terms often are used interchangeably, but it is important to distinguish the difference between the definition of HAC and
Cushing's syndrome. HAC is defined as an overproduction of steroid hormones from the adrenal cortex. Cushing's syndrome refers
to HAC with excess production of cortisol. Finally, atypical Cushing's disease refers to HAC caused by increased levels of
intermediate adrenal steroids (aka sex steroids.)
Jack Oliver, DVM, PhD,, reviews this syndrome in the ACVIM Forum Proceedings 2007 471-473. "Steroid Profiles in the Diagnosis
of Canine Adrenal Disorders."
Signs associated with HAC range from subtle to profound, and may be seen in both traditional and atypical disease. Excessive
panting sometimes is the only client concern (Table 1). Other disease processes can cause clinical signs associated with HAC,
so it is important to rule out different inflammatory, metabolic and neoplastic processes before initiating therapy. Baseline
CBC, biochemical profile, urine analysis/culture, thyroid hormone profile and radiographs/ultra- sonographic imaging are recommended
in these cases.
Various tests are advocated as screening and differentiating tools to identify those patients with HAC characterized by increased
Despite clinical impressions and supportive laboratory data, some dogs with HAC fail to be diagnosed with these tests. It
is now clear that steroids other than cortisol influence the hypo- thalamic-pituitary axis and cause clinical signs.
Researchers have investigated measurement of serum 17-hydroxyprogesterone concentration alone after ACTH administration as
an additional tool to identify those dogs. Ristic J.M.E, et al. (OR Ramsey, I.K., Heath, F.M., Evans, H.J., Herrtage. M.E.)
The Use of 17-Hydroxyprogesterone in the Diagnosis of Canine Hyperadrenocorticism. J Am Vet Med Assoc. 2002; 16: 433-439.
Mixed results indicate that quantification of additional intermediate steroids is warranted. The Clinical Endocrinology Service
at the University of Tennessee performs adrenal function testing. Those dogs with certain abnormal steroid profiles/ adrenal
sex hormone excess have been characterized as atypical Cushing's cases. Atypical cushingoid dogs may have pituitary or adrenal-dependent
Currently, steroids measured in the adrenal panel are cortisol, androstendione, estradiol, progesterone, 17-OH progesterone
and aldosterone. An abbreviated production pathway is shown in Figure 1.
One hypothesis explaining abnormal elevations of these steroids in dogs with primary adrenal tumors is an increased and continuous
stimulatory effect of luteinizing hormone causing adrenocortical tumor development. Oliver notes human studies show that some
hyperplastic or neoplastic adrenal tissue may be under control of various ectopic or aberrant hormone receptors.
The adrenal panel is performed using the ACTH stimulation test protocols using either ACTH Gel or Cortrosyn®. Cortisol and
five other steroid values are reported for each sample. For more detailed information go to (
http://www.vet.utk.edu/diagnostic/endocrinology/) and view written protocol for the adrenal function ACTH stimulation test.
Treatment options include the familiar Lysodren®, ketoconazole and, more recently, trilostane.
In some cases, especially if alopecia is present, melatonin supplementation may be instituted. Clinical results may not be
appreciated for two to three months. Though melatonin is inexpensive, response to treatment is sometimes equivocal.