Cushing's Disease

CUSHING’S DISEASE -

Cushing’s disease may also be referred to as Hyperadrenocorticism (HAC) or Cushing’s Syndrome by your vet. Cushing’s syndrome means that your pet has clinical signs attributed to the overproduction of glucocorticoids. There are three situations that can cause this:  the administration of steroids by your vet, a pituitary tumor, or an adrenal gland tumor. Glucocorticoids are produced by the two adrenal glands that are located in the abdomen near the kidneys and are necessary to sustain life. The pituitary gland, located in the brain, sends the adrenal glands a message to produce more glucocorticoids when the body requires it. If there is a pituitary tumor, it may send extra messages causing the adrenal glands to produce more than is needed by the body. Likewise, if there is an adrenal gland tumor it will produce the hormone without obeying any signal from the pituitary gland to stop. Glucocorticoids aid in metabolism and decrease inflammation. An overproduction of glucocorticoids can decrease water absorption by the body, break down fat and muscle tissue, increase metabolism, and cause immunosuppression.

Symptoms

Most owners will notice that their pet is drinking a lot of water and urinating frequently. This is caused by the blockage of vasopressin by the glucocorticoids. Vasopressin helps the body to reabsorb fluids. Without it, most fluids are lost through urination and your pet will drink large amounts to try and compensate for the loss. There is often a concurrent urinary tract infection because the urine is too dilute to combat bacteria.  Because of the increased metabolism, your pet will be hungry and in many cases will have an enlarged liver that is trying to produce more glucose for the body to use for food. For this reason, you may notice a distended abdomen. Since steroids break down muscle and fat tissue, the abdomen may appear pot-bellied and weak. Owners may also notice that there is hair loss, comedones and hard stone-like bumps in their pet’s skin called calcinosis-cutis. The immunosuppressive effects of steroids will allow more infections to occur, and we generally see a lot of scaling, crusting skin.

Diagnosis

Clinical signs usually give us a high index of suspicion for the disease. If only hair loss and weight gain are noted, we may check your pet for hypothyroidism first which may cause similar signs and is easier to treat. Routine bloodwork may suggest Cushing’s disease, but it is not definitive enough to make a diagnosis.

The two tests we routinely perform are the ACTH stimulation test and the low dose dexamethasone suppression test (LDDS). We will ask you to fast your pet for 8 hours prior to the test. The ACTH test is very specific and if it is positive, your pet has the disease. The problem is that it is not very sensitive and if the result comes back negative, your pet may still have the disease. The LDDS is not as specific, but it is much more sensitive. This means that it may turn out positive when your pet does not have the disease! For this reason, both tests may be done on different days.  In the case of Atypical Cushing’s disease, we may even opt for a third test to look for hormones other than glucocorticoids that an overactive adrenal gland may be producing. It is complicated and even after all that testing, we may recommend that a high-dose dexamethasone suppression test be done to differentiate between a pituitary and adrenal tumor. Your vet will choose the test that is best for your pet.

Treatment

If the clinical signs of the disease are due to excess steroid administration by your vet, a slow tapering of the medication will halt the progression of the disease. This must be done slowly or the adrenal glands will not remember how to produce the glucocorticoids and your pet may suffer from a serious disease called hypoadrenocorticism. If your pet is diagnosed with pituitary-dependent hyperadrenocorticism (PDH) there is no cure, only management of the disease.   The drug Mitotane (Lysodren) is quite effective and works to destroy adrenal tissue.  Therefore, even though the pituitary gland is telling the adrenal gland to produce more hormone, it cannot. This drug can be toxic if overdosed so extensive monitoring and bloodwork is necessary. The goal is to eventually administer the drug on a weekly basis. Another option is a drug called ketoconazole.  This drug works to inhibit steroid synthesis by the adrenal gland. It is expensive and must be given twice daily or its effects will discontinue when administration is withdrawn. If your pet is diagnosed with adrenal-dependent hyperadrenocorticism (ADH) it is recommended that the affected gland be removed, as these are more likely to be cancerous. Determination of the affected gland and any associated metastasis can be done by ultrasound. Treatment with mitotane and ketoconazole are also options to control the clinical signs. A new drug, Anipryl (l-deprenyl) was recently approved for treating Cushing’s disease. It does not appear to be as toxic as Lysodren or as effective.