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Cushing's and Addison's disease: Testing and management (Proceedings)

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Apr 01, 2010



Addison's disease and Cushing's syndrome are opposite sides of the same coin. Both are manifestations of dysfunction of the adrenal glands. The adrenals, located right next t o the kidneys (ad-renal), are a pair of glands that secrete several hormones. There are three layers of the adrenals: the zona glomerulosa, zona fasciculata, and zona reticulosa, from exterior to interior. Characteristic hormones from these layers are aldosterone (glomerulosa), which controls sodium balance in the body, cortisol (fasciculate), a major steroid in the body, and sex hormones (reticulosa). The adrenal glands are stimulated to secrete their products by the pituitary via signaling with ACTH.

Addison's disease

The overwhelming majority of cases of Addison's disease (hypoadrenocorticism) are due to a primary failure of the adrenals. While a deficiency of sex hormones aren't often clinically significant in our patients, a deficiency of aldosterone, the product of the zona glomerulosa, and cortisol, a product of the zona fasciculata, can be significant and life threatening. In the absence of aldosterone, sodium and potassium become disregulated, causing hyponatremia and hyperkalemia. In addition to the direct life threatening effects of these electrolyte disorders, volume depletion associated the electrolyte imbalances can cause hypovolemic shock. Absence of cortisol can initially be more subtle: causing malaise, inappetance, and failure to thrive. However, with prolonged cortisol deficiency and stress, weakness, significant gastrointestinal ulceration, and anorexia can result.

Diagnosis


Table 1: ACTH stimulation test protocol.
After recognizing the possibility of Addison's disease, diagnosis is straightforward. A basal cortisol level can first be evaluated. If cortisol is greater than 2 ug/dL, it is extremely unlikely Addison's disease is present. Normal dogs can have low basal cortisols as well, therefore, if basal cortisol is low, a supraphysiologic dose of ACTH must be administered and cortisol levels are measured afterwards. If the adrenals are within normal limits, they will respond to the stimulation of the ACTH and the post cortisol level will be increased. In an Addison's patient, the adrenals are incapable of responding to even a supraphysiologic dose and post ACTH cortisol levels will be flat as with the pre level. Salient points of the ACTH stimulation test are listed in table 1.

Note that synthetic ACTH is preferred product due to variability in ACTH gel products. Dexamethasone administered during a crisis situation will not cross react with the assay. However, long term administration of ANY steroid will blunt the adrenal response.

Treatment


Table 2: Common options for treatment of typical Addison‘s disease.
Replacement of glucocorticoids is the hallmark of the management of Addison's disease. Additionally, mineralocorticoid deficiency must be addressed in all dogs with typical Addison's. The most common treatment options for Addison's disease are listed in table 2, along with pro's and con's of each. It should be noted, that a very small minority of dogs treated with DOCP may not need prednisone as listed, however, this is uncommon.

Prognosis for dogs with typical Addison's disease is excellent if they have committed owners willing to deal with the initial titration phase and vigiliantly monitor their pets.