Risk for thrombotic events high after Cushing’s syndrome surgery

Approximately 20% of a cohort of adults with Cushing’s syndrome experienced at least one thrombotic event after undergoing pituitary or adrenal surgery, with the highest risk observed for those undergoing bilateral adrenalectomy, according to findings from a retrospective analysis published in the Journal of the Endocrine Society.

“We have previously showed in a recent meta-analysis that Cushing’s syndrome is associated with significantly increased venous thromboembolic events odds vs. the general population, though the risk is lower than in patients undergoing major orthopedic surgery,” Maria Fleseriu, MD, FACE, professor of neurological surgery and professor of medicine in the division of endocrinology, diabetes and clinical nutrition in the School of Medicine at Oregon Health & Science University and director of the OHSU Northwest Pituitary Center, told Healio. “However, patients undergoing many types of orthopedic surgeries have scheduled thromboprophylaxis, especially postsurgery, which is not the standard of care in patients with Cushing’s syndrome. In this study, we wanted to look in more detail at the rates of all thrombotic events, both arterial and venous, in patients at our specialized pituitary center over more than a decade.”

In a retrospective, longitudinal study, Fleseriu and colleagues analyzed data from 208 individuals with Cushing’s syndrome undergoing surgical (pituitary, unilateral and bilateral adrenalectomy) and medical treatment at a single center (79.3% women; mean age at presentation, 45 years; mean BMI, 33.9 kg/m²; 41.8% with diabetes). Individuals with severe illness and immediate mortality were excluded. Thromboembolic events (myocardial infarction, deep venous thrombosis [DVT], and pulmonary embolism or stroke) were recorded at any point up until last patient follow-up. Researchers assessed all patients who received anticoagulation in the immediate postoperative period and up to 3 months after surgery, recording doses and complications for anticoagulation.

Within the cohort, 39 patients (18.2%) experienced at least one thromboembolic event (56 total events; 52% venous), such as extremity DVT (32%), cerebrovascular accident (27%), MI (21%), and pulmonary embolism (14%). Of those who experienced a thromboembolic event, 40.5% occurred within 60 days of surgery.

Researchers found that 14 of 36 patients who underwent bilateral adrenalectomy experienced a thromboembolic event, for an OR of 3.74 (95% CI, 1.69-8.27). Baseline 24-hour urinary free cortisol levels did not differ for patients with or without thromboembolic event after bilateral adrenalectomy.

“Despite following these patients over time, results almost surprised us,” said Fleseriu, also an Endocrine Today Editorial Board Member. “The risk of thromboembolic events in patients with Cushing’s syndrome was higher than we expected, approximately 20%. Many patients had more than one event, with higher risk at 30 to 60 days postoperatively. Use of a peripherally inserted central catheter line clearly increased risk of upper extremity DVT.”

Among 197 patients who underwent surgery, 50 (25.38%) received anticoagulation after surgery with 2% experiencing bleeding complications.

“We clearly need to understand more about what happens in patients with Cushing’s syndrome for all comorbidities, but especially thrombosis, and find the factors that predict higher risk and use anticoagulation in those patients,” Fleseriu said. “We have shown that among patients who had anticoagulation, risks were minimal. We also have to think more about timelines for these thromboembolic events and the duration of anticoagulation, and probably to expand it up to 30 to 60 days postoperatively if there are no contraindications, especially for patients undergoing bilateral adrenalectomy.”

Fleseriu cautioned that the findings do not necessarily suggest that every individual with Cushing’s syndrome needs anticoagulation therapy, as the study was retrospective. Additionally, sex, age, BMI, smoking status, estrogen or testosterone supplementation, diabetes and hypertension — all known factors for increased thrombosis risk among the general population — were not found to significantly increase the risk for developing a thromboembolic event, Fleseriu said.

“As significantly more patients have exogenous Cushing’s syndrome than endogenous Cushing’s syndrome and many of these patients undergo surgeries, we hope that our study increased awareness regarding thromboembolic risks and the need to balance advantages of thromboprophylaxis with risk of bleeding,” Fleseriu said. – by Regina Schaffer

For more information:

Maria Fleseriu, MD, FACE, can be reached at fleseriu@ohsu.edu.

Disclosure: Fleseriu reports she has received research funding paid to her institution from Novartis and Strongbridge and has received consultant fees from Novartis and Strongbridge.

 

From  https://www.healio.com/endocrinology/neuroendocrinology/news/online/%7Bce267e5a-0d32-4171-abc8-34369b455fcf%7D/risk-for-thrombotic-events-high-after-cushings-syndrome-surgery

Post-traumatic Stress Symptoms Common in Cushing’s Patients Before Surgery

Patients with Cushing’s disease may develop post-traumatic stress symptoms, which are generally resolved once they undergo surgery to remove the tumor, but can persist in some cases, a study shows.

The study, “Posttraumatic stress symptoms (PTSS) in patients with Cushing’s disease before and after surgery: A prospective study,” was published in the Journal of Clinical Neuroscience.

Cushing’s disease is an endocrine disorder characterized by excess secretion of the adrenocorticotropic hormone (ACTH) by a pituitary adenoma (tumor of the pituitary gland). This leads to high levels of cortisol, a condition known as hypercortisolism.

Chronic hypercortisolism is associated with symptoms such as central obesity, buffalo hump, body bruising, muscle weakness, high blood pressure, high blood sugar, and weak bones.

Additionally, patients can develop psychiatric disorders including depression, anxiety, and cognitive dysfunction, all of which contribute considerably to a lower health-related quality of life.

Depression and anxiety rates are particularly high in Cushing’s disease patients, with 54% of them experiencing major depression and 79% having anxiety.

Due to the significant impact of psychological factors in these patients, they may be susceptible to post-traumatic stress symptoms (PTSS). But more information on this phenomenon in these patients is still needed.

To address this lack of data, a group of Chinese researchers conducted a prospective study to investigate the occurrence, correlated factors, and prognosis of PTSS in patients with Cushing’s disease.

A total of 49 patients newly diagnosed with Cushing’s disease who underwent transsphenoidal removal of the tumor as their first-line treatment were asked to participate in this study. Another group of 49 age- and sex-matched healthy individuals were included as controls.

PTSS was measured using the Impact of Event Scale-Revised (IES-R), depression/anxiety were measured using the Hospital Anxiety and Depression scale (HADS), and quality of life was measured using the 36-item short-form (SF-36). These parameters were measured before surgery, and then at six and 12 months after the procedure.

Before surgery, 15 patients (30.6%) had PTSS. These patients also had higher cortisol levels, worse levels of depression/anxiety, and worse quality of life scores than those without PTSS.

While most of the patients recovered after the operation, there were five (33.3%) for whom PTSS persisted for more than a year.

Additionally, one patient who had a recurrence of Cushing’s disease developed PTSS between six and 12 months after the first surgery.

PTSS severity showed consistent improvement after surgery, which was correlated with better depression/anxiety scores and psychological aspects of the SF-36. However, Cushing’s disease patients in remission still performed worse than healthy individuals concerning their physical and mental health.

Therefore, “patients with [Cushing’s disease] can develop PTSS, and they may persist for over a year even after successful surgery. Combined psychological intervention is advised for these patients,” the researchers concluded.

From https://cushingsdiseasenews.com/2019/06/25/cushings-patients-often-have-post-traumatic-stress-symptoms

Even in Remission, Cushing’s Patients Have Excess Mortality

Cushing’s disease patients in Sweden have a higher risk of death than the general Swedish population, particularly of cardiovascular complications, and that increased risk persists even in patients in remission, a large nationwide study shows.

The study, “Overall and disease-specific mortality in patients with Cushing’s disease: a Swedish nationwide study,” was published in the Journal of Clinical Endocrinology and Metabolism.

The outcomes of Cushing’s disease patients have improved with the introduction of several therapeutic approaches, such as minimally invasive surgery and cortisol-lowering therapies. However, mortality is still high, especially among those who do not achieve remission.

While currently patients in remission are thought to have a better prognosis, it is still unclear whether these patients still have a higher mortality than the general population. Understanding whether these patients are more likely to die and what risk factors are associated with increased mortality is critical to reduce death rates among Cushing’s patients.

A team of Swedish researchers thus performed a retrospective study that included patients diagnosed with Cushing’s disease who were part of the Swedish National Patient Registry between 1987 and 2013.

A total of 502 patients with Cushing’s disease were included in the study, 419 of whom were confirmed to be in remission. Most patients (77%) were women; the mean age at diagnosis was 43 years, and the median follow-up time was 13 years.

During the follow-up, 133 Cushing’s patients died, compared to 54 expected deaths in the general population — a mortality rate 2.5 times higher, researchers said.

The most common causes of death among Cushing’s patients were cardiovascular diseases, particularly ischemic heart disease and cerebral infarctions. However, infectious and respiratory diseases (including pneumonia), as well as diseases of the digestive system, also contributed to the increased mortality among Cushing’s patients.

Of those in remission, 21% died, compared to 55% among those not in remission. While these patients had a lower risk of death, their mortality rate was still 90% higher than that of the general population. For patients who did not achieve remission, the mortality rate was 6.9 times higher.

The mortality associated with cardiovascular diseases was increased for both patients in remission and not in remission. Also, older age at the start of the study and time in remission were associated with mortality risk.

“A more aggressive treatment of hypertension, dyslipidemia [abnormal amount of fat in the blood], and other cardiovascular risk factors might be warranted in patients with CS in remission,” researchers said.

Of the 419 patients in remission, 315 had undergone pituitary surgery, 102 had had their adrenal glands removed, and 116 had received radiation therapy.

Surgical removal of the adrenal glands and chronic glucocorticoid replacement therapy were associated with a worse prognosis. In fact, glucocorticoid replacement therapy more than twice increased the mortality risk. Growth hormone replacement was linked with better outcomes.

In remission patients, a diagnosis of diabetes mellitus or high blood pressure had no impact on mortality risk.

Overall, “this large nationwide study shows that patients with [Cushing’s disease] continue to have excess mortality even after remission,” researchers stated. The highest mortality rates, however, were seen in “patients with persistent disease, those who were treated with bilateral adrenalectomy and those who required glucocorticoid replacement.”

“Further studies need to focus on identifying best approaches to obtaining remission, active surveillance, adequate hormone replacement and long-term management of cardiovascular and mental health in these patients,” the study concluded.

From https://cushingsdiseasenews.com/2019/02/28/even-in-remission-cushings-patients-have-excess-mortality-swedish-study-says/

Rare Disease Day 2019

rare disease day

 

Each and every day since 1987,  I tell anyone who will listen about Cushing’s.  I pass out a LOT Cushing’s business cards. My husband also passes out cards and brochures.

Adding to websites, blogs and more which I have maintained continuously since 2000 – at mostly my own expense.

Posting on the Cushing’s Help message boards about Rare Disease Day.  I post there most every day.

Tweeting/retweeting info about Cushing’s and Rare Disease Day today.

Adding info to one of my blogs about Cushing’s and Rare Disease Day.

Adding new and Golden Oldies bios to another blog, again most every day.

Thinking about getting the next Cushing’s Awareness Blogging Challenge set up for April…and will anyone else participate?

And updating https://www.facebook.com/CushingsInfo with a bunch of info today (and every day!)

~~~

Today is Rare Disease Day.

I had Cushing’s Disease due to a pituitary tumor. I was told to diet, told to take antidepressants and told that it was all my fault that I was so fat. My pituitary surgery in 1987 was a “success” but I still deal with the aftereffects of Cushing’s and of the surgery itself.

I also had another Rare Disease – Kidney Cancer, rare in younger, non-smoking women.

And then, there’s the secondary adrenal insufficiency…and growth hormone deficiency

If you’re interested, you can read my bio here: https://cushingsbios.com/2018/10/28/maryo-pituitary-bio/

What are YOU doing for Rare Disease Day?

 

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Cushing’s Disease Patients with USP8 Mutations More Likely to Achieve Remission After Surgery

Cushing’s disease patients whose pituitary tumors carry a USP8 mutation are more likely to achieve remission after surgery than those without such mutations, a retrospective Italian study found.

The study, “Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas,” was published in the journal Endocrine.

Cushing’s disease is a condition where a tumor on the pituitary gland produces too much of the adrenocorticotropin hormone (ACTH), which will act on the adrenal gland to make cortisol in excess.

While rare, the condition can be life-threatening, as excess cortisol is linked to an increased risk of infections and cardiovascular complications, along with an increased likelihood of obesity and diabetes.

The reasons some patients develop these pituitary adenomas are far from understood, but researchers recently found that some of these patients show mutations in the USP8 gene. These appear to increase EGFR signaling which, in turn, has a stimulatory role for the synthesis of ACTH.

But more than influencing the development of Cushing’s disease, researchers believe the USP8 mutations may also determine response to treatment.

Thus, a team in Italy examined whether patients with USP8 mutations presented different clinical features and responded differently to the standard surgical procedure, called transsphenoidal pituitary surgery.

The study included 92 patients with ACTH-secreting pituitary tumors who received surgery at the neurosurgical department of the Istituto Scientifico San Raffaele in Milan between 1996 and 2016.

“All surgical procedures were performed by the same experienced neurosurgeon, which is one of the most important factors affecting early and late surgical outcome of pituitary adenomas,” researchers explained.

Among study participants, 22 (23.9%) had mutations in the USP8 gene, but these mutations were significantly more common in women than in men — 28.7% vs. 5.3%. Researchers think estrogens — a female sex hormone — may have a role in the development of mutated pituitary tumors.

Overall, the two groups had similar tumor size and aggressiveness and similar ACTH and cortisol levels before surgery. But among those with microadenomas — tumors smaller then 10 mm in diameter — USP8-mutated patients had significantly larger tumor diameters.

After receiving surgery, 81.5% of patients achieved surgical remission — deemed as low cortisol levels requiring glucocorticoid replacement therapy, normal cortisol levels in urine, and normal response to a dexamethasone-suppression test.

But remission rates were significantly higher among those with USP8 mutations — 100% vs. 75.7%. Also, USP8 mutation carriers required steroid replacement therapy for shorter periods, despite ACTH and cortisol levels being similar among the two groups after surgery.

Among patients who entered remission, 12 (16%) saw their disease return. While more patients with USP8 mutations experienced a recurrence — 22.7% vs. 13.2% — this difference was not significant. After five years, 73.8% of UPS8-mutated patients remained alive and recurrence-free, which researchers consider comparable to the 88.5% seen in patients without the mutation.

Researchers also tested sex, age at surgery, and post-surgical ACTH and cortisol levels as possible predictors of disease recurrence, but none of these factors was associated with this outcome.

“ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated on by a single neurosurgeon. Recurrence rates are not related with USP8-variant status,” researchers concluded.

From https://cushingsdiseasenews.com/2018/10/23/cushings-disease-patients-usp8-mutations-more-likely-achieve-remission-after-surgery/

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