Hyperadrenocorticism

Diagnosis of spontaneous canine hyperadrenocorticism:  2012 ACVIM Consensus Statement (Small Animal) J Vet Intern Med 2013; 27:1292-1304.

Canine adrenocortical hyperfunction is suspected frequently from history, clinical signs, hematologic and biochemical changes (e.g., steroid-induced alkaline phosphatase).  Approximately 80% of canine hyperadrenocorticism (HAC) cases are the result of a pituitary tumor, and 20% are the result of an adrenal tumor.

The diagnosis of HAC is based on: 1. clinical findings; 2. screening test results; 3. discrimination test results.

1. Screening tests are the low-dose dexamethasone suppression (LDDS) test, the ACTH stimulation test, or the urinary cortisol:creatinine ratio.  The LDDS test is more sensitive and allows distinction between pituitary and adrenal origin in ~60% of dogs.

2.    Discrimination tests are the high-dose dexamethasone suppression test (HDDS) and the endogenous ACTH assay. These discrimination tests may not be necessary if ‘partial suppression’ (i.e., suppression to <50% of baseline or <40 nmol/L at 3 or 4 h) is noted with the low-dose dexamethasone suppression test (LDDS), thus supporting a diagnosis of pituitary origin hyperadrenocorticism.

A.  Low-dose dexamethasone suppression (LDDS) test (0.01 mg/kg)

Procedure:

1.  Commence test between 08:00 & 09:00 h.

2.  Collect 3.5 mL of blood in serum tube.  Do not use SST blood collection tubes.

3.  Inject 0.01 mg dexamethasone/kg intravenously.

4.  Collect additional serum samples at 3 or 4 h and 8 h.

5.  Centrifuge the samples immediately and freeze the serum until analyzed.

Interpretation: (per Michigan State University)

Normal dogs:  Serum cortisol suppresses to <40 nmol/L for the 8 h interval.

Adrenocortical hyperfunction:  Dogs with HAC do not suppress to <40 nmol/L for the full 8 h.  In ~60% of dogs with pituitary tumors, there is suppression to <50% baseline values or <40 nmol/L at 3 or 4 h.

B.  ACTH stimulation test

Procedure:

1.  Collect blood sample in serum tube for resting cortisol.  Do not use SST blood collection tubes.

2.  Inject synthetic ACTH analog (e.g., cortrosyn at dose of 1-5 µg/kg IV).

3.  Collect blood sample in serum tube at 1 h post-injection.

4.  Centrifuge samples and freeze the serum until analyzed.

Interpretation:

Normal dogs:  Cortisol will increase above 250 nmol/L, but not above 600 nmol/L.

Adrenocortical hyperfunction:  Serum cortisol will increase to >600 nmol/L if pituitary or hypothalamic origin.  A response between 250 and 600 nmol/L does not rule out HAC.

Adrenocortical hypofunction:  Resting cortisol <30 nmol/L and post-ACTH response <50 nmol/L.

C.  Urinary cortisol/creatinine ratio

This is an additional screening test for HAC in dogs with normal renal function.  The test is sensitive for HAC, but non-specific and should only be used to rule out HAC.  Stress or disease will increase urinary cortisol output, which may result in a false-positive result; this limits the diagnostic utility of this test.

Procedure:

Collect early morning urine samples, preferably on 2 consecutive days and at home.  Refrigerate samples until tested for cortisol and creatinine concentrations.

Interpretation: 

        Normal dogs:  Cortisol/creatinine ratio <10 X 10-6.

D.  High-dose dexamethasone suppression (HDDS) test (0.1 mg/kg)

This test is used to differentiate adrenal from pituitary causes of adrenocortical hyperfunction, after this diagnosis has been established.

Procedure:

1.  Commence test between 08:00 & 09:00 h.

2.  Collect 3-5 mL of blood in serum tube. Do not use SST blood collection tubes.

3.  Inject 0.1 mg dexamethasone /kg IV.

4.  Collect serum cortisol samples at 4 and 8 h.

5.  Centrifuge the samples immediately and freeze the serum until analyzed.

Interpretation: (per Michigan State University)

About 75% of dogs with pituitary tumors suppress to <40 nmol/L or <50% baseline cortisol levels at 4 or 8 h.  Dogs with

adrenal tumors rarely suppress cortisol production.  In ~25% of cases, testing of pituitary-adrenal axis function does not allow identification of the source of hypercortisolemia, and imaging studies or endogenous ACTH determination may be required.

E. Endogenous adrenocorticotropic hormone (ACTH) assay in dogs: ACTH is a labile hormone that requires meticulous handling. Blood should be collected into a chilled silicone-coated EDTA tube, centrifuged immediately, the plasma then transferred into a plastic (nylon) tube, and kept frozen until assayed. Endogenous ACTH may help differentiate pituitary- dependent from adrenal-dependent hyperadrenocorticism. Values <4.4 pmol/L are consistent with adrenal origin HAC, values > 18 pmol/L are consistent with pituitary origin.

F. Feline HAC: The LDDS test (at 0.1 mg of dexamethasone/ kg) is recommended as the screening test of choice in evaluating a cat for hyperadrenocorticism. HDDS (at 1.0 mg/kg) can be used to distinguish pituitary from adrenal origin.