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Cushing's Disease (Hyperadrenocorticism)

Background:Cushing's disease is actually an assortment of symptoms caused by excessive levels of cortisol or related steroids in the body.  Cortisol is a stress hormone that has effects on virtually every tissue and organ in the body.

There are three main forms of Cushing's disease.  Pituitary Dependent Cushing's is caused by a tumor (usually small and benign) of the pituitary gland in the brain overstimulating the adrenal glands.  Adrenal tumors can be benign or malignant and produce cortisol independent of pituitary stimulation.  Iatrogenic Cushing's is caused by over medicating with cortisol-like drugs such as prednisone and numerous types of eye, ear, and topical skin medications.

Symptoms:The earliest and most common symptoms of Cushing's disease are increased urination and water consumption, often with a concurrent increase in appetite.  Other possible signs include poor skin and hair condition, muscle atrophy, increased abdominal fat, enlarged liver, chronic or recurrent infections (especially skin or urinary), delayed wound healing, excessive panting, sodium retention (which can cause high blood pressure or exacerbate congestive heart failure, and occasionally diabetes.  Some dogs show no symptoms.

Diagnosis:Suspicion of Cushing's disease usually begins with a history of excessive water consumption and urination with or without other symptoms.  Other cases may begin with laboratory abnormalities found while investigating other problems or with presurgical or routine screening tests.  Abnormalities that are commonly seen in Cushing's patients are:  Elevated liver enzymes (Alk Phos, +/-ALT), +/- increased blood glucose, unconcentrated urine (specific gravity less that 1.025), protein in urine, Alterations in blood cell counts (increased neutrophils, decreased lymphocytes and eosinophils), and +/- nucleated red blood cells.

If Cushing's disease seems likely, one or more specific tests are done to confirm or rule out, and to distinguish between the three types described above.  These tests are:  Low Dose Dexamethasone Suppression, High Dose Dexamethasone Suppression, ACTH stimulation, endogenous ACTH,  Abdominal/adrenal gland ultrasound, and extended panel ACTH stimulation.

If symptoms are absent or mild, no treatment may be necessary.  However, establishing a diagnosis makes management of other problems (infections, surgical or other wounds) more effective.  If symptoms or recurrent infections are present, treatment is based on the specific type of Cushing's disease diagnosed. 
Iatrogenic Cushing's is treated by gradually reducing or eliminating the source of excess corticosteroid medications and using alternate treatments in their stead.
Pituitary Cushing's is treated with medications.  Mitotane (Lysodren) is used to destroy the adrenal tissue producing the excess cortisol.  This is generally very effective but must be monitored closely to avoid over-treatment, which can have serious side effects.  A new treatment that may soon be available is Trilostane, which may be associated with less risk of side effects.
Adrenal tumors are generally best removed surgically.  If this is not feasible for any reason, suppression of the tumor with Lysodren is sometimes effective.  A new approach is to use Lysodren at very high doses to totally destroy the adrenal tissue, leaving the patient permanently adrenal-insufficient and  requiring regular supplementation of cortisol and other adrenal hormones.  Though few patients have been treated in this manner, it appears to be well tolerated and as good a long term outlook as other (surgical) treatments.

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