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Cushing’s Disease

Aug 19, 2018
by Dr. Michael Trapani


You have to be some kind of doctor to have a disease named after you. The bizarre thing about Harvey Williams Cushing is that his discovery of Cushing’s disease isn’t even counted as his greatest accomplishment. Cushing is considered the Father of Neurosurgery and is credited with the introduction of blood pressure measurement to North America. He won a Pulitzer Prize and a Lister Medal. Among his bazillion other honors, he appeared on a United States postage stamp and was nominated for the Nobel Prize at least 38 times.

But it’s Cushing’s disease that makes the name something of a household word. In an era that has largely abandoned eponymous naming, Cushing’s disease stands out as an exception, possibly because Cushing’s original term, “polyglandular syndrome” and the modern term, “hyperadrenocorticism” don’t exactly roll off the tongue. Let’s give it to the old boy. Heis the Father of Neurosurgery, after all.

Cushing’s disease causes Cushing’s syndrome, a specific cluster of signs that results from a chronic systemic overdose of cortisol. The adrenal glands are the source of cortisol and other steroids, which are crucial to normal body function. When the body is exposed to excessive amounts of these hormones, lots of bad things happen. Thirst in increased, causing elevated water intake and increased urination. Appetite is increased, causing weight gain and both accumulation and redistribution of body fat. Blood sugar levels are elevated, promoting diabetes, glaucoma, and cataracts. Muscle mass declines, and as muscle weakness advances, the abdomen becomes distended. The liver accumulates fat and enlarges, and blood levels of liver enzymes increase, sometimes to the point of hepatopathy (liver dysfunction). Atrophy of skin and hair follicles cause the appearance of thin, delicately wrinkled skin and hair loss. In more severe cases, soft tissue mineralization leads to the development of sores and hard calcium plaques within the skin (calcinosis cutis). Excessive cortisol is immunosuppressive, promoting infections in many locations. This is only a partial list of signs seen in in the disease. Cushing’s patients may show any or none of them.

There are three main ways to acquire the disease:The most common form results from the development of an adenoma (a glandular tumor) on the pituitary gland at the base of the brain. Most (but not all) of these tumors are small, and make their presence known through the secretion of ACTH (adrenocorticotrophic hormone - you had to ask). ACTH stimulates the adrenal glands to secrete excessive amounts of cortisol and there you have it: Cushing’s disease. Much less commonly, a malignant adenoma of the adrenal gland itself can over secrete cortisol and cause the disease. These tumors tend to be nasty little suckers that like to invade the vena cava and send giant blood clots to the heart. Not good. The much, much less common way to acquire Cushing’s disease is to have your doctor give it to you by prescribing long-term, high doses of prednisone or another steroid medication. This is the reason we need to be so careful with drugs of the “cortisone” family. Yes, they can be life-saving, but nothing this powerful can be used without risk.

Cushing’s disease can be difficult to recognize.There are a number of other problems that can promote the same kinds of signs, and subtle cases of the disease may be quite, well… subtle. The definitive test is an ACTH stimulation test, where exogenous ACTH is administered at a standard dose and the patient’s increase in cortisol secretion is compared to a normal population. But even this seemingly straight-forward form of testing is not always completely reliable. Sometimes we have to test the patient’s response tosuppression of the adrenal gland. Adrenal function testing is a can of worms that can be confusing to even seasoned diagnosticians.

Once the diagnosis has been made, treatment of most Cushing’s disease patients if fairly straightforward. There are several medications available to suppress adrenal secretion of cortisol. Once hormone levels have been normalized the great majority of patients return to normal, although some changes generated by Cushing’s disease, such as diabetes or cataracts, are typically permanent. Malignant adrenal gland tumor patients are particularly difficult to help because the tumors are located so close to the kidney, the aorta, and the vena cava, and because these tumors tend to invade nearby tissues early in the disease. Even when the hormone secretion problem is managed, the malignant character of these tumor’s behavior severely limits how much we can help.

It took one heck of a doctor to figure this out. Harvey Cushing deserves every honor bestowed upon him, and a lot more. How about that Nobel Prize? It’s about time.


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