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Cardiovascular Complications of Cushing’s Syndrome

Cushing’s syndrome is characterized by chronic overproduction of cortisol by the adrenal glands. The most frequent cause of Cushing’s syndrome is a benign pituitary tumor (adenoma) that produces adrenocorticotropic hormone (ACTH), which, in turn, stimulates the adrenal glands. Other causes are tumors elsewhere in the body that produce ACTH and adrenal tumors that produce cortisol. Cortisol is a glucocorticoid hormone that influences every organ system of the body.

Cardiovascular Risk Factors

Chronic exposure to high cortisol levels leads to a wide range of signs and symptoms and ultimately long-term complications. One of the most important complications of Cushing’s syndrome involves cardiovacular disease. Cushing’s syndrome is often accompanied by cardiovascular risk factors, including obesity, hypertension (high blood pressure), diabetes mellitus (high blood glucose levels), and high blood lipid levels. This clustering of cardiovascular risk factors can also occur in the general population and is known as the metabolic syndrome. In addition, high cortisol levels may have direct toxic cardiovascular effects. If untreated, these risk factors can cause thickening of the arterial vessel walls, a process called atherosclerosis. On top of this narrowing, complete blockage of the vessel can occur as a result of a blood clot, which is defined as arterial thrombosis. Occlusion of coronary and cerebral arteries results in myocardial and cerebral infarction, respectively. Meanwhile, it has been established that patients who are not or not completely cured from Cushing’s syndrome remain at risk for cardiovascular disease. This mainly involves patients with a pituitary adenoma.

Treatment and Cardiovascular Risk

Surgery is the primary treatment option for patients with Cushing’s, but if pituitary surgery fails, it is very important to normalize cortisol production by radiotherapy or medical therapy. If radiotherapy is the chosen therapeutic option, medical therapy will frequently also be necessary, at least temporarily, because radiotherapy has a delayed onset of action. Unfortunately, in some patients cardiovascular factors persist despite successful treatment. It is important to treat these risk factors with medical therapy with tight control of blood pressure, glucose, and lipid levels. In addition to an increased risk of arterial thrombosis, it has become apparent in recent years that patients with active Cushing’s syndrome are also at risk for venous thrombosis. Blockage of the veins mainly occurs in the veins of the leg, which is known as deep venous thrombosis or DVT, and the lung, which is known as pulmonary embolism or PE. Also, patients who choose surgery for a pituitary adenoma have a high risk of venous thrombosis in the postoperative period and need treatment with low-molecular-weight heparin to prevent thrombosis.

Author: Dr. Richard A. Feelders MD (Summer, 2013)

Editor’s Note: Richard Feelders, MD, PhD is an Associate Professor of Endocrinology at the Erasmus University Medical Center, Rotterdam, The Netherlands, where he is also chair of the Pituitary Center Rotterdam and coordinator of the ENETS GEP-Neuroendocrine Tumor Center Rotterdam. Dr. Feelders main fields of patient care and scientific interest involve the diagnosis and medical treatment of Cushing’s syndrome.


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