Properly Diagnosing Addisons Disease and Your Dogs Treatment Options
The adrenals are two small glands positioned next to the kidneys. The center of each gland is called the medulla and the outer area is called the cortex.
The adrenal medulla secretes the “fight or flight” hormones: adrenaline (also called epinephrine) and noradrenaline (also called norepinephrine). These hormones are generally not affected by Addison’s disease, which affects only those secreted by the adrenal cortex: glucocorticoid and mineralocorticoid hormones. Addison’s can cause deficiencies of both types of steroid hormones.
Glucocorticoids (primarily cortisol) affect nearly every tissue in the body. They help maintain blood pressure and cardiovascular function, activate the body’s stress response, regulate metabolism and blood glucose levels, stimulate appetite, modify red and white blood cell production, and promote a general sense of well-being. Glucocorticoid levels are controlled by adrenocorticotropic hormone (ACTH), which is produced by the pituitary gland.
Mineralocorticoids (primarily aldosterone) are responsible for regulating electrolytes (sodium, potassium, and chloride) and water balance, which affects blood pressure. Electrolytes also affect nerve and muscle function, including heart rate and rhythm.
Typical Addison’s, often called primary Addison’s, is caused by adrenal dysfunction that creates both glucocorticoid and mineralocorticoid deficiencies. The adrenal glands atrophy, usually because of an autoimmune response that may be hereditary. Other possible causes include granulomatous disease, tumors, injury, prescription drug side effects, infection, or inflammation. By the time symptoms appear, an estimated 85 to 90 percent of the adrenal cortex has been destroyed. Dogs with typical Addison’s will have electrolyte imbalances, but this alone is not enough to diagnose the disease, nor can normal electrolytes rule out Addison’s disease.
In atypical Addison’s, the adrenal cortex continues to produce aldosterone but not cortisol. Patients with atypical Addison’s have normal sodium and potassium levels. Most eventually progress to typical Addison’s disease within a few months or, in some cases, years.
In secondary Addison’s, the pituitary gland no longer produces ACTH because of immune-mediated damage, inflammation, trauma, or cancer. Similar to atypical Addison’s, only cortisol production is affected, but secondary Addison’s will never progress to the typical form of the disease. Because aldosterone is still produced by the adrenal cortex, secondary Addison’s disease does not cause electrolyte imbalances.
Addison’s disease can be brought on by treatment for Cushing’s disease designed to suppress or destroy overactive adrenal glands. The antifungal medication ketoconazole is sometimes used to treat Cushing’s because it suppresses adrenal function. The sudden withdrawal of prednisone or other cortisone medications after long-term use can also trigger an Addisonian crisis.
The ACTH (adrenocorticotropic hormone) response (or stimulation) test is considered definitive for Addison’s. Dogs must be off all corticosteroid hormones except dexamethasone for at least 12 to 36 hours (or more, if they’ve been on steroids for a long time) to prevent the drugs from affecting test results.
The cortisol level of an initial blood sample is measured; then the dog is injected with a form of the pituitary hormone ACTH that signals the adrenals to produce cortisol. One hour later, the blood cortisol level is measured again. In healthy dogs, cortisol levels rise, indicating a normal adrenal response. If the dog’s initial cortisol level is low and there is little or no response after ACTH stimulation, the diagnosis is Addison’s disease.
Synthetic ACTH (cosyntropin, Cortrosyn) is preferred for consistency; ACTH gels are not recommended for this test, because the results may not be accurate. An older protocol used one vial (250 mcg) of Cortrosyn for every dog, but only 5 mcg/kg is needed to achieve maximal adrenal stimulation when given intravenously. This can translate into a substantial cost saving for small dogs.
If the ACTH response test is positive and electrolytes are normal, then a separate test to measure endogenous ACTH levels can differentiate between primary and secondary Addison’s. Endogenous ACTH levels will be greatly elevated with primary Addison’s but low or undetectable with secondary Addison’s. Dogs with secondary Addison’s will never develop electrolyte abnormalities, making treatment and monitoring much less expensive.
Two situations can result in a misdiagnosis of Addison’s disease. Dogs from breeds originating around the Pacific Rim, including the Akita, Shiba Inu, and Jindo, often have elevated potassium values. This can be confused with Addison’s, particularly when symptoms are similar.
Whipworms can create a syndrome nearly identical to Addison’s, including low sodium and elevated potassium. Fecal tests for whipworms are often negative because eggs are shed infrequently.
In both cases, ACTH response tests will be normal. Always confirm a diagnosis of Addison’s disease before beginning mineralocorticoid supplementation.
In Addisonian crisis, treatment with intravenous fluids, glucocorticoids such as dexamethasone, and sometimes glucose as well can literally save a dog’s life. Once the patient’s condition has stabilized, treatment moves to the life-long replacement of adrenal hormones, along with careful monitoring of electrolyte levels for dogs with typical Addison’s.
Glucocorticoid hormones such as prednisone, prednisolone, methyl-prednisolone (Medrol), or hydrocortisone are needed for all Addisonian dogs. For atypical and secondary Addison’s, this is the only drug prescribed. Prednisolone and methylprednisolone have been converted to a bioactive form, a process which otherwise must be done by the liver, so these may be good choices for dogs with elevated liver enzymes. Methylprednisolone and hydrocortisone may be associated with fewer side effects. Hydrocortisone is synthetic cortisol, closest to the natural form.
The starting dose is 0.1 to 0.2 mg prednisone (0.4 to 0.8 mg hydrocortisone) per pound of body weight daily. This is a physiologic dose, meant to mimic the amount of cortisol the body would produce itself if it were able. It should not cause the type of side effects associated with prednisone given at therapeutic levels for dogs with problems such as allergies or autoimmune disorders.
Many dogs do well on 0.05 mg prednisone (0.04 mg Medrol, 0.2 mg hydrocortisone) per pound of body weight daily. Even large dogs usually do not require more than 5 mg daily, except during times of stress. The dosage is best divided in half and given every 12 hours in order to keep cortisol levels more even, particularly when using hydrocortisone, which has a much shorter half-life.
Dogs with typical Addison’s also need mineralocorticoid supplementation. Two options are available: fludrocortisone acetate (Florinef) and desoxycorticosterone pivalate (DOCP, commonly known by the brand name Percorten-V).
Florinef is an oral medication that is given once a day in the morning or split into two daily doses. Missing even a single dose can be dangerous. It can be difficult to regulate dogs taking Florinef, and increases in the initial dosage are frequently required, especially during the first year, as any remaining adrenal function is lost.
Percorten-V is given by subcutaneous injection once every 25 days or so. Experts find that in addition to having fewer side effects, Percorten-V regulates electrolytes more effectively than Florinef. Dogs who have problems when taking Florinef, including excessive thirst, urination, or incontinence, may do better with Percorten-V.
Aiyana, the Italian Greyhound who was finally diagnosed with Addison’s disease, was initially treated with Florinef. “Her electrolytes wouldn’t stabilize, and she didn’t respond as expected,” says Kunzler. “My vet switched her to Percorten-V injections, which has made a lot of difference.”
Dogs on Percorten-V require glucocorticoid supplements, such as prednisone, in addition to their monthly injections. Fludrocortisone has some glucocorticoid activity, so about half of the dogs who take this medication do not require regular glucocorticoid supplements, and others may need supplements every two or three days rather than daily.
All dogs with Addison’s need additional glucocorticoids during times of stress, injury, or illness. What constitutes stress will vary from one dog to another. Stress can be physiological, such as a medical procedure, injury, or even a particularly active play session. Stress can also be emotional, such as from a move, the loss of a human or animal companion, thunderstorms, fireworks, a visit to the vet’s office, or anything that disrupts familiar routines.
Stress increases the need for glucocorticoids from two to four times the maintenance level. A dog undergoing surgery may need even more, starting with a high dose and quickly tapering back to normal during the following week. An alternative would be to give an injection of dexamethasone during surgery, followed by oral steroids after. Fluid support should always be provided for Addisonian dogs during surgery.
Next: Monitoring Treatment