After Cushing’s Surgery, Patients May Be at High Risk for Blood Clots

Case report recommends preventive anti-blood clotting treatments

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Patients who undergo surgery for Cushing’s syndrome may have a high risk of blood clots and should receive preventive anti-blood clotting treatments for at least one month, according to a recent case report.

Researchers also suggested these patients should be closely monitored following surgery.

The report described the case of a woman who developed four blood clots in one leg — a condition called deep vein thrombosis — after undergoing surgery to remove a pituitary gland tumor, which had caused her to develop Cushing’s disease.

“This case highlights the need for further research on risk factors associated with thrombosis in Cushing’s syndrome and the importance of updated guidelines to address this issue,” the researchers wrote.

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The study, “Multiple deep vein thromboses after curative surgery for Cushing’s disease: A case presentation and review,” was published in the journal AACE Clinical Case Reports.

Cushing’s syndrome is caused by increased levels of the hormone cortisol in the body, often as a result of tumors in the adrenal glands sitting stop the kidneys, or in the brain’s pituitary gland. In many cases, patients undergo surgery to remove these tumors.

Increased risk of blood clots

Cortisol excess can lead to changes in blood clotting, with studies demonstrating that people living with Cushing’s have a 10–18 times higher risk of developing blood clots compared with the general population.

These patients are particularly susceptible to deep vein thromboses, a type of blood clot that develops in the veins of the legs, groin, or arms, and can then travel and lodge in the lungs.

Moreover, studies have shown that this clotting risk increases substantially after surgery.

However, guidelines on how to prevent these episodes are not clear and their clinical management is variable, according to researchers.

Now, a team in the U.S. described the case of a patient with Cushing’s disease who experienced four deep vein thromboses after undergoing surgery to remove a pituitary tumor.

The 57-year-old woman came to the researchers’ clinic in New York with reports of abdominal pain a month after having gastric bypass surgery for weight loss. The woman had a history of type 2 diabetes and high blood pressure over the previous two years.

A CT scan of her abdomen revealed abscesses, or infected areas filled with pus. She was treated with antibiotics and the abscesses were drained.

In the hospital, doctors found she had high blood pressure, despite her usual medications, as well as low blood potassium levels that were unresponsive to potassium supplements.

At that time, the patient reported that she had experienced excessive hair growth, difficulty climbing stairs, and easy bruising during the prior two weeks.

An exam showed coarse hair on her chin, fat accumulation in the abdomen and between her shoulder blades, skin discoloration, and weakness in the muscles closer to the center of the body — e.g. the upper arms and legs. All of these are symptoms associated with Cushing’s.

Laboratory tests revealed additional signs of Cushing’s, including elevated blood adrenocorticotropic hormone (ACTH) — the hormone released from the pituitary gland that signals the adrenal glands to produce more cortisol. The woman also was found to have excess cortisol in the blood and urine.

A low dose of the steroid dexamethasone minimally lowered her cortisol levels, a hallmark sign of Cushing’s syndrome. A higher dose could partially lower them.

The patient responded to a corticotropin-releasing hormone (CRH) stimulation test, which is used as a way of determining that the likely cause of excess ACTH is a pituitary tumor. A brain MRI confirmed the presence of such a tumor.

Just prior to surgery to remove the tumor, a blood coagulation test showed that her blood was clotting faster than normal. After surgery, her cortisol levels dropped.

The woman was given heparin — a blood thinner used to prevent blood clots — and hydrocortisone, a steroid. She was discharged home nine days after surgery, at which time heparin was stopped. Clotting tests, however, still revealed faster-than-usual clotting.

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Higher clotting risk post-surgery

Five days later, she came to the emergency room with swelling and pain in her left leg. She was found to have four deep vein thromboses, for which she was treated with the blood thinner apixiban.

At an appointment two months later, her factor VIII activity levels — a blood clotting protein — were 217% of normal. Factor VIII, typically called FVIII, is a protein involved in the cascade of molecular events that leads to blood clotting. Six months later, this value had normalized to 121% of normal.

These findings overall highlight the increased risk of blood clots after surgery to correct Cushing’s disease, consistent with previous reports for Cushing’s syndrome patients.

Researchers noted, however, that despite this higher risk, clear guidelines for clinicians are lacking.

“Identifying the highest risk patients remains a challenge, and practice patterns still vary significantly among pituitary experts who report prescribing anticoagulation [anti-clotting] after surgery for anywhere from 1-2 days of the hospital stay up to 2–3 months,” the researchers wrote.

Based on this case and previous findings, the team noted “it is reasonable to recommend thromboprophylaxis [preventive treatment] for at least 1 month, especially in cases of severe [Cushing’s].”

The risk of blood clots “persists for at least a month after surgery,” the researchers wrote in making a case for improved post-surgical monitoring of patients.