Canine Hypoadrenocorticism – Addison’s Disease

Diagnosis

Primary hypoadrenocorticism results when more than 90% of both adrenal cortices are destroyed and this leads to a clinical deficiency of all adrenal hormones. The ACTH stimulation test will provide confirmation of Addison’s. It is also useful to measure the Sodium/Potassium ratio as evidence for mineralocorticoid deficiency. A low Na:K ratio may not be seen in some cases of primary hypoadrenocorticism until a very advanced stage of the disease. That is, an animal can have confirmed primary hypoadrenocorticism without abnormal electrolytes. Animals with a secondary hypoadrenocorticism (deficient pituitary production of ACTH) would not be expected to have electrolyte disturbance.

ACTH Stimulation Test

  1. Collect basal blood sample.
  2. Immediately inject 0.25 mg synthetic ACTH (Synacthen) i/v or i/m
  3. Collect a second blood sample one hour later.
  4. Label samples clearly and request Cortisol analysis.

Interpretation

The basal cortisol will be low with little or no response after ACTH. A classic Addison’s ACTH response test would be Pre cortisol = <20 nmol/L, Post cortisol = <20 nmol/L. False positive diagnoses occur in animals which have been receiving glucocorticoid therapy recently including oral, injectable and topical (eye, ear and skin) preparations. For confirmation of primary hypoadrenocorticism in dogs which have been receiving glucocorticoid therapy, consider measuring aldosterone instead of, or in addition to, cortisol.
Prednisolone, prednisone and hydrocortisone will cross-react in the cortisol assay and give falsely elevated results. Such therapies should be avoided in the 24 to 36 hours prior to the test. Dexamethasone does not have this effect so it can safely be used prior to confirmation of diagnosis without causing assay interference. However, prolonged use (several days) of dexamethasone prior to performing the ACTH response test can increase the risk of false positive diagnosis and require the measurement of aldosterone for confirmation.

Endogenous (plasma) ACTH
ACTH concentrations can be useful in distinguishing primary from secondary hypoadrenocorticism (see differentiation in Canine hyperadrenocorticism section). Dogs with primary Addison’s have very high levels of ACTH, usually greater than 500 pg/mL. Dogs with secondary Addison’s have low or undetectable (< 5.0 pg/mL) levels of ACTH.

Aldosterone
Aldosterone measurement may also be used to differentiate between primary and secondary Addison’s and this can be performed on the same samples used to measure the cortisol, with no difference in sample handling procedures.
In primary hypoadrenocorticism, there will be failure of both glucocorticoid and mineralocorticoid production. In secondary hypoadrenocorticism (pituitary ACTH production failure, exogenous steroids) glucocorticoid production will have failed but mineralocorticoid production is unaffected. The trophic support for mineralocorticoid production comes from the renin-angiotensin system not ACTH. However, there is a sufficient aldosterone response to ACTH stimulation to use this as a dynamic diagnostic test for mineralocorticoid production which has advantages over measuring baseline aldosterone alone.

Monitoring therapy

The laboratory monitoring of primary hypoadrenocorticism focuses on electrolyte status. There is no value in repeating ACTH stimulation tests in animals which have failed adrenal glands. The artefactual cortisol concentrations generated from the cross-reaction of prednisolone in the assay are not biologically equivalent and so a cortisol assay cannot assess the adequacy of glucocorticoid therapy. Biologically equivalent cortisol results can be obtained only during periods that hydrocortisone is the exclusive corticosteroid therapy.
The monitoring of secondary hypoadrenocorticism is based mostly on clinical response with periodic attempts to find the lowest glucocorticoid dose at which the animal appears well. Liver enzyme analysis can help identify steroid hepatopathy resulting from glucocorticoid excess.