Treating Dogs with Hypoadrenocorticism (Addison's Disease)

Addison's disease, the common name for hypoadrenocorticism or adrenal insufficiency, as I have discussed in my last two blog posts, is a disease with vague clinical features that are common in many other ailments, making diagnosis difficult in many cases. But once Addison's disease is correctly diagnosed, a properly treated dog can live a normal and happy active life.

The missing adrenal hormones

The adrenal, one on each kidney, is made up of two layers, the cortex and the medulla. The inner medulla secretes epinephrine (adrenaline) and is not affected by Addison's disease. The outer cortex layer secretes two corticosteroid hormones, cortisol and aldosterone, both of which are deficient in Addison's disease.

Aldosterone is a corticosteroid hormone (more specifically, a mineralocorticoid — think minerals: salt, sodium, potassium) responsible for maintaining normal circulating electrolyte levels. Once secreted, aldosterone acts on the kidney to conserve sodium, excrete potassium, and retain needed water.

Cortisol is also a corticosteroid hormone (in this case, a glucocorticoid — think glucose, sugar, energy) that is essential for life. It supports a variety of important cardiovascular, metabolic, immunologic, and stress functions.

Not all forms of hypoadrenocorticism are treated the same
There are three forms of hypoadrenocorticism: primary, secondary and atypical Addison's disease.

1. Primary Addison's disease is most commonly is the result of immune-mediated damage to the glands.
2. Atypical Addison's disease is a poorly understood disorder, thought to generally be an early stage of primary Addison's disease.
3. Secondary hypoadrenocorticism results from a deficiency of the pituitary hormone, adrenocorticotropic hormone (ACTH). Without circulating ACTH, cortisol cannot be secreted by the adrenal glands.

It is important which form of hypoadrenocorticism is present in order to provide the correct treatment. In primary hypoadrenocorticism, both cortisol and aldosterone are deficiency and must be replaced for life. In atypical and secondary hypoadrenocorticism, on the other hand, only the glucocorticoids need to be replaced, at least initially.

Treating the acute adrenal crisis: A true medical emergency
Untreated, hypoadrenocorticism (especially primary Addison's disease) can lead to an adrenal crisis. An adrenal crisis is a medical emergency that requires intravenous fluids and glucocorticoids to restore the body’s levels of fluids, salt, and sugar to normal.

Once stabilized, the dog can then be treated with glucocorticoid and mineralocorticoid replacement therapy at home.

Treating chronic hypoadrenocorticism: A lifelong disease
Depending of the subtype of hypoadrenocorticism, synthetic corticosteroid drugs that act like mineralocorticoid or glucocorticoids used for hormone replacement therapy.

Mineralocorticoid treatment

For mineralocorticoid (aldosterone) replacement, either an oral medication called fludrocortisone acetate (Florinef™) or the injectable desoxycorticosterone pivalate (DOCP; Percorten-V™) is used.

We typically institute treatment with DOCP (Percorten-V) at a dosage of 2.2 mg/kg, subcutaneously or intramuscularly, every 25 to 30 days. Side effects associated with DOCP therapy are rare. This dosage interval is effective in almost all dogs, and most are well controlled with a DOCP injection every 4 weeks.

Initially, serum kidney and electrolyte concentrations should be monitored at approximately 2-weeks intervals in order to determine the drug’s peak effect and to help make necessary dosage adjustments. Once stabilized, serum electrolyte and creatinine concentrations are checked every 3 to 6 months. Because DOCP is a pure mineralocorticoid and has no glucocorticoid activity, it is essential that dogs receive concurrent glucocorticoid supplementation (see below).

Fludrocortisone is a synthetic corticosteroid that possesses moderate glucocorticoid activity as well as having marked mineralocorticoid potency. By comparison, fludrocortisone has 10 times the glucocorticoid activity and 125 times the mineralocorticoid activity of cortisol. In this regard, fludrocortisone is very different than DOCP, which possess no glucocorticoid activity.

If fludrocortisone acetate is employed as mineralocorticoid supplementation, we recommend an initial oral dosage of approximately 0.02 mg/kg/day.

After initiation of fludrocortisone therapy, serum electrolyte and creatinine concentration should be monitored weekly, with the dosage adjusted by 0.05-0.1 mg/day increments until values have stabilized within the reference range. Once this is achieved, the dogs should be reevaluated monthly for the first 3 to 6 months of therapy, then every 3 to 6 months thereafter.

For dogs that have atypical or secondary Addison’s, mineralocorticoid replacement therapy with DOCP or fludrocortisone aren't needed because the production of aldosterone isn’t effected and the serum electrolytes remain in balance.

Glucocorticoid treatment

In addition to replacing deficient mineralocorticoids in dogs with Addison's disease, the missing glucocorticoids must also be replaced. This is typically done with an oral form of the synthetic glucocorticoids prednisone, prednisolone, or hydrocortisone. With atypical Addison's and secondary forms of hypoadrenocorticism, glucocorticoid replacement is all that is needed, at least initially, since these dogs do not have serum electrolyte abnormalities.

 The correct dose of the supplemented glucocorticoids, such as prednisone, cannot be measured with a blood test. Rather it's determined by your observations: the lowest dose that keeps your dog symptom free, happy and eating! The most common side effect of overdosage is an increase in thirst and urination, which can be intense in some dogs.

Prognosis of Addison's disease

With proper treatment, the long-term prognosis is excellent. While your dog with Addison’s disease will need medications and monitoring for the rest of his life, most dogs with Addison’s can return to their favorite activities. You will help your dog lead a normal, active and fun-filled life.