Hyperadrenocorticism, commonly referred to as “Cushing’s Disease”, is a disease caused by an overproduction of cortisol from the adrenal glands and can occur in two different forms: pituitary-dependent hyperadrenocorticism or an adrenal gland tumor.
The pituitary gland (a small structure located at the base of the brain) secretes a hormone called ACTH which causes the adrenal glands (located next to the kidneys) to secrete cortisol and other hormones. In normal dogs, the cortisol ‘feeds back’ to the pituitary gland and decreases the ACTH produced. If there is a tumor present on the pituitary gland (pituitary dependent hyperadrenocorticism), the ACTH levels are not decreased by even the highest levels of cortisol. Therefore, there is an overproduction of cortisol. In dogs, pituitary tumors occur in 85-90% of patients with hyperadrenocorticism, where tumors of the adrenal gland occur in 10-15% of patients. Those caused by pituitary tumors are usually treated with oral medication.
The adrenal tumors are removed surgically.
Hyperadrenocorticism can be diagnosed by blood tests. There are different types of tests available that provide different kinds of information. There is a 1-hour test called an ACTH stimulation test which requires two different blood samples to be taken and an injection to be given. There is also an 8-hour test which requires 3 separate blood samples to be taken. In some patients, multiple tests are required. Since endocrine diseases are very dynamic, these tests may need to be repeated to verify if the disease is present. An abdominal ultrasound may also be recommended.
There are many complications of hyperadrenocorticism, some of which can be life threatening. These include: pyelonephritis (kidney infection), congestive heart failure, diabetes mellitus, pulmonary thromboemboli (blood clots), liver enzyme elevations, inability to concentrate urine, hair loss, muscle weakness and recurrent skin infections.
Since there is no medical therapy for shrinking the size of the pituitary gland, the adrenal glands (source of cortisol) are the target for medication. The most common form of therapy for Cushing’s is the drug Lysodren (mitotane), which ‘shrinks’ the adrenal glands so that it cannot produce as much cortisol.
Lysodren may be given in 2 phases. The first phase is the ‘loading phase.’ Lysodren is given daily for 5-14 days. In this phase the adrenal gland size is decreased quickly. An ACTH stimulation test is performed on the 9th or 10th days to determine if the adrenal glands have decreased enough to produce the desired level of cortisol secretion.
The ACTH stimulation test is done to check the response of the adrenal gland. If the cortisol levels are appropriate, Lysodren will be continued less frequently, 1-2x/week (maintenance or second phase). If the levels are not appropriate, the loading phase may be continued for a longer period. Ideally, recheck ACTH stimulation tests will be performed at one-month, three-month, then six-month intervals to determine if the cortisol levels remain within normal range. Many patients may be treated initially with the maintenance dose to avoid potential loading phase complications.
Lysodren has many potentially serious side effects which may include: vomiting, diarrhea, severe listlessness or lethargy, collapse and stupor. If any of these signs are ever noted, call your veterinarian or an emergency clinic (if after hours). Vomiting may be due to gastric irritation or due to decreasing the size of the adrenal glands too much. Lysodren must always be given with a meal to enhance absorption.
Trilostane is an oral medication that is given once or twice daily. Bloodwork is monitored (including an ACTH stimulation test) after any initiation or change in dosing. Once cortisol levels are controlled, monitoring is done every 3-6 months. ACTH stimulation tests must be done 4-6 hours after trilostane administration.
Other therapies such as ketoconazole, deprenyl, melatonin and/or lignans may be prescribed for Cushing’s therapy. If this is indicated, your veterinarian will discuss these medications and changes in testing procedures at that time.
Improvement of clinical signs involving the skin may require 3-4 months after the levels are within normal range.