Richard W. Nelson, DVM, DACVIM
Findings from the history and physical examination are the first indicators for hyperadrenocorticism and results of a complete blood count, serum biochemistry panel, and urinalysis provide further evidence for performing tests to evaluate the pituitary-adrenocortical axis. The primary indication for pursuing a diagnosis of hyperdrenocorticism is dogs with one or more of the common clinical signs and physical examination findings listed in Table 1; the more abnormalities identified, the stronger the indication to pursue diagnostic testing.
Table 1. Clinical manifestations of hyperadrenocorticism in dogs
No hair regrowth
Pituitary macrotumor syndrome
Facial nerve palsy
Less common clinical signs and physical examination findings add further support for diagnostic testing, but do not, when identified by themselves and without any of the common findings, support testing for hyperadrenocorticism in lieu of pursuing more likely differentials.
Findings on a complete blood count, serum biochemistry panel and urinalysis usually provide further evidence for hyperadrenocorticism (Table 2).
Table 2. Common abnormalities in routine blood and urine tests
Complete blood count
Serum biochemistry panel
Increased alkaline phosphatase
Increased alanine aminotransferase
Urine specific gravity ≤ 1.018
Indicators of urinary tract infection
None of the abnormalities listed in Table 2 are pathognomonic for hyperadrenocorticism. All are routinely identified with other diseases in the dog. Results of the CBC, biochemistry panel and urinalysis must always be interpreted within the context of the history and findings on physical examination.
Tests to establish the diagnosis of hyperadrenocorticism include the urine cortisol/creatinine ratio (UCCR), the low-dose dexamethasone suppression (LDDS) test, and the ACTH stimulation test. Baseline serum cortisol measurement, by itself, is of no diagnostic value in diagnosing hyperadrenocorticism. Discriminatory tests to identify the etiology [i.e., pituitary-dependent (PDH) vs. adrenal-dependent hyperadrenocorticism caused by a cortisol-secreting adrenocortical tumor (ADH)] include the low- and high-dose dexamethasone suppression test and baseline endogenous ACTH concentration.
Urine Cortisol/Creatinine Ratio (UCCR)
The UCCR is an excellent initial screening test for hyperadrenocorticism in dogs. UCCRs should be determined from free-catch urine samples obtained by the client in the non-stressful home environment on 2 consecutive mornings. Any normal UCCR is a strong finding against hyperadrenocorticism; however, an increased UCCR is not diagnostic of hyperadrenocorticism. The specificity of the UCCR is low in dogs. Additional tests are indicated when both UCCRs are increased, or when one UCCR is normal but the clinical picture strongly suggests hyperadrenocorticism.
Low-dose Dexamethasone Suppression (LDDS) Test
The LDDS test is a reliable diagnostic test for differentiating normal dogs from those with hyperadrenocorticism and may identify pituitary-dependent hyperadrenocorticism (PDH). Sensitivity and specificity are approximately 90%. False positive and false negative results occur with this test. Results of the LDDS test may be affected by concurrently administered anticonvulsant drugs, stress, excitement, exogenous glucocorticoids, and nonadrenal disease. For the LDDS test, 0.01 mg of dexamethasone/kg body weight is administered IV and blood obtained immediately prior to, and 4 and 8 hours after dexamethasone administration. The 8-hour post-dexamethasone serum cortisol concentration is used to confirm hyperadrenocorticism. Normal dogs typically have serum cortisol values less than 28 nmol/L; usually < 14 nmol/L, whereas dogs with PDH and ADH have serum cortisol concentrations greater than 42 nmol/L 8 hours after dexamethasone administration. Cortisol concentrations between 28 and 42 nmol/L are non-diagnostic and do not definitively rule out hyperadrenocorticism.
If the 8-hour serum cortisol value supports a diagnosis of hyperadrenocorticism, the 4-hour serum cortisol value may then be of value in identifying PDH. Low doses of dexamethasone suppress pituitary ACTH secretion and serum cortisol concentrations in approximately 60% of dogs with PDH. Suppression does not occur in dogs with ADH nor does it occur in approximately 40% of dogs with PDH. Suppression is defined as a 4-hour serum cortisol concentration less than 42 nmol/L, a 4-hour serum cortisol concentration less than 50% of the baseline concentration, or an 8-hour serum cortisol concentration less than 50% of the baseline concentration. Any dog that meets one or more of these criteria most likely has PDH. If none of these criteria are met, results of the LDDS test have not differentiated between PDH and ADH.
Oral Dexamethasone Suppression Test
An alternative 'at home' oral dexamethasone suppression test relies entirely on results of UCCRs to establish the diagnosis of hyperadrenocorticism and to identify PDH. The owner is instructed to collect 2 urine samples from the dog on 2 consecutive mornings and store them in the refrigerator. After collection of the second urine sample, the owner should administer 3 doses of dexamethasone (0.1 mg/kg/dose) to the dog orally at 8-hour intervals. Urine is collected on the morning of the third day and UCCR is determined on all 3 samples. The first 2 urine samples establish the diagnosis of hyperadrenocorticism; both results must be abnormal. If both values are abnormal, then the average of the 2 values are used as the 'baseline' value and compared with the third value obtained after dexamethasone administration. A diagnosis of PDH is established if the UCCR result from the third urine sample is less than 50% of the 'baseline' value. Dogs failing to meet these criteria could have either ADH or PDH.
ACTH Stimulation Test
Because of problems with sensitivity and specificity and the common occurrence of false positive and false negative test results, I do not use the ACTH stimulation test when evaluating dogs for naturally acquired hyperadrenocorticism. I have had dogs with post-ACTH cortisol concentrations greater than 1300 nmol/L that did not have hyperadrenocorticism.
High-dose Dexamethasone Suppression Test
The protocol for the high-dose dexamethasone suppression test is similar to that for the LDDS test protocol, except that a higher dose (i.e., 0.1 mg/kg of body weight) of dexamethasone is used in an attempt to suppress pituitary ACTH secretion. Suppression is defined as a 4-hour or 8-hour serum cortisol concentration less than 42 nmol/L, and a 4-hour or 8-hour serum cortisol concentration less than 50% of the baseline concentration.
Endogenous ACTH Concentration
I do not routinely measure plasma ACTH concentrations, except when needed to provide clarity in confusing cases where test results for hyperadrenocorticism and findings on abdominal ultrasound conflict. For example, a dog with an adrenal mass but suppression on the LDDS test or a dog with an adrenal mass, enlargement of the contralateral adrenal gland, and lack of suppression on the LDDS test. Determination of a baseline plasma ACTH concentration is not used to diagnose hyperadrenocorticism. Determination of a single baseline plasma ACTH concentration may aid in distinguishing dogs with ADH from those with PDH once the diagnosis of hyperadrenocorticism is established. Adrenocortical tumors and iatrogenic hyperadrenocorticism should suppress ACTH secretion and results should be low or undetectable. PDH is the result of excessive ACTH secretion and results should be in the reference range or increased.