Cushing's disease is a disease in which the adrenal glands overproduce certain hormones. Another medical term for this disease is hyperadrenocorticism. The adrenal glands produce several vital substances, which regulate a variety of body functions and are necessary to sustain life. The most widely known of these substances is cortisol, commonly known as
cortisone. Either deficient production or excessive production of these substances may be life-threatening.
Cushing's disease is a form of Cushing's syndrome that is caused by an ACTH secreting pituitary adenoma. About 10% of pituitary adenomas secrete excess ACTH. This elevated ACTH in turn stimulates the adrenal glands to produce excess cortisol. This disease process is called Cushing's disease (named after the famous neurosurgeon, Harvey Cushing).
There are three mechanisms by which this disease can occur. Regardless of the cause, the clinical signs are essentially the same. It is important to identify the cause, however, because the various forms are treated differently and have different prognoses.
Pituitary gland tumor. The most common cause of Cushing's Disease (85% of all cases) is a tumor of the pituitary gland. The tumor may be either benign or malignant. The tumor causes the pituitary to overproduce a hormone, which stimulates the adrenal glands. Excessive cortisone secretion results. The tumor may be either microscopic or quite large. Depending on the size of the tumor, the presence of signs other than Cushing's will be variable. Generally, if the activity of the adrenal gland can be controlled, many dogs with this form of Cushing's Disease can live normal lives for many years as long as they take their medication and stay under close medical supervision. Growth of the pituitary tumor would give the patient a less favorable prognosis.
Adrenal gland tumor. Cushing's Disease may be the result of a benign or malignant tumor of the adrenal gland. If benign, surgical removal cures the disease. If malignant, surgery may help for a while, but the prognosis is less favorable than for a benign tumor.
Iatrogenic. Iatrogenic Cushing's Disease means that the excess of cortisone has resulted from excessive administration of cortisone. This may occur from oral or injectable medications. Although the injections or tablets were given for a legitimate medical reason, their excess is now detrimental.
Cushing's disease has a myriad of signs and symptoms, many of which are listed in Table 1. Cushingoid features are often pronounced but may be subtle in some cases. ACTH secreting pituitary adenomas are often small (less than 10 mm) at the time of discovery but, if large, may manifest with "mass effects" (visual field disturbances, headaches, pituitary hormone deficiencies, etc). Cortisol influences virtually every cell in the body and Cushing's patients often complain of severe dysfunction due extreme fatigue and weakness. Many of the features of Cushing's disease are common to other diseases (non-specific symptoms) and thus Cushing's patients often suffer for years prior to appropriate diagnosis.
A number of tests are necessary to diagnose and confirm Cushing's Disease. The primary one is the ACTH Stimulation Test. If it does not confirm the diagnosis, the Low-Dose Dexamethasone Suppression Test is performed. Other tests are needed to decide which form of the disease is present. An ultrasound examination can be a valuable part of the testing process. This permits us to visualize the adrenal gland tumor and determine its size. Although some of these tests are somewhat expensive, they are necessary.
There are two main phases that a cured patient will go through after surgery. The first is the cortisol withdrawal phase. The features of Cushing's disease are due to cortisol excess and the body reacts to having the cortisol withdrawn. To make the process tolerable (and safe), large doses of glucocorticoids are given to the postoperative patient and then tapered over a month or so as symptoms allow. This can be an awful experience for the patient marked by fatigue, depression, and body aches. Headache may be present but if severe (especially if accompanied by nausea and dizziness) may indicate that the taper is happening to quickly. After the initial withdrawal phase, the second phase is marked by the temporary need for continued glucocorticoid replacement (typically 20 mg hydrocortisone or 5 mg prednisone) until the hypothalamic/pituitary/adrenal (HPA) axis awakens. This phase may last many months and may last over a year. Until this axis awakens, the patient is adrenally insufficient and should be treated accordingly.