Osilodrostat normalizes urinary free cortisol in Cushing’s disease for most at 72 weeks

Posted on September 19, 2022 by MaryO

More than 80% of adults with Cushing’s disease receiving osilodrostat had normalized mean urinary free cortisol levels at 72 weeks of treatment, according to findings from the LINC 3 study extension.

“Cushing’s disease is a chronic condition, and many patients require prolonged pharmacological treatment. Therefore, evaluating long-term efficacy and safety of drug therapies in clinical trials is essential,” Maria Fleseriu, MD, FACE, professor of medicine and neurological surgery and director of the Pituitary Center at Oregon Health & Science University in Portland and a Healio | Endocrine Today co-editor, told Healio. “Our findings build on the positive results of the LINC 3 study core phase, and it was reassuring to see that continued treatment with osilodrostat for over 72 weeks provided long-term normalization of cortisol levels. Furthermore, continued treatment with osilodrostat also led to sustained improvements in clinical signs and physical manifestations of hypercortisolism, as well as health-related quality of life, which are all important factors in the management of these patients.”

Fleseriu and colleagues enrolled 106 adults with Cushing’s disease who were responders to osilodrostat (Isturisa, Recordati) at 48 weeks during the LINC 3 core study to enter the extension phase of the trial. Participants continued to receive open-label osilodrostat until 72 weeks or treatment discontinuation. Mean urinary free cortisol was collected every 12 weeks. Physical manifestations of hypercortisolism were rated at 48 and 72 weeks. Participants completed the Cushing’s Quality of Life questionnaire and Beck Depression Inventory II at 48 and 72 weeks. Adults were deemed to have completely responded to treatment if mean urinary free cortisol was less than the upper limit of normal and partially responded to treatment if mean urinary free cortisol was above the upper limit of normal but decreased more than 50% from baseline.

The findings were published in the European Journal of Endocrinology.

Of the 106 participants in the extension study, 98 completed 72 weeks of treatment. At 72 weeks, 81.1% of participants were complete responders to treatment, and reductions in mean urinary free cortisol from the core phase were maintained during the extension.

Improvements in most cardiovascular and metabolic-related parameters from the core study were maintained or improved in the extension phase. The cohort also had increases in quality of life score and improvements in Beck Depression Inventory II scores.

The proportion of participants with improvements in physical manifestation of hypercortisolism were maintained or improved in all areas at 72 weeks. For hirsutism in women, 86.4% had an improved or stable severe score at 72 weeks. Improved scores were observed in participants with mild, moderate and severe physical manifestations at baseline with few adults experiencing worse manifestations at the end of the extension study.

There were no new safety signals reported in the extension study. Of the extension study participants, 11.3% discontinued osilodrostat due to adverse events, a similar percentage to the 10.9% discontinuation rate during the core phase of the study.

Several hormone concentrations, including mean adrenocorticotropic hormone, 11-deoxycortisol and plasma aldosterone, stabilized during the extension phase after changes were observed in the core study compared with baseline. Mean testosterone in women decreased from 2.6 nmol/L at 48 weeks to 2.1 nmol/L at 72 weeks. There were no changes observed in mean testosterone levels for men.

“Patients should be regularly monitored and osilodrostat dose titrated as necessary, alongside adjustment of concomitant medications, to optimize outcomes,” the researchers wrote. “Taken together, these findings support osilodrostat as an effective and well-tolerated long-term treatment option for patients with Cushing’s disease.”

For more information:

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

From https://www.healio.com/news/endocrinology/20220914/osilodrostat-normalizes-urinary-free-cortisol-in-cushings-disease-for-most-at-72-weeks

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Updated Cushing’s disease guideline highlights new diagnosis, treatment ‘roadmap’

Posted on November 15, 2021 by MaryO

An updated guideline for the treatment of Cushing’s disease focuses on new therapeutic options and an algorithm for screening and diagnosis, along with best practices for managing disease recurrence.

Despite the recent approval of novel therapies, management of Cushing’s disease remains challenging. The disorder is associated with significant comorbidities and has high mortality if left uncontrolled.

Adrenal transparent _Adobe
Source: Adobe Stock

“As the disease is inexorable and chronic, patients often experience recurrence after surgery or are not responsive to medications,” Shlomo Melmed, MB, ChB, MACP, dean, executive vice president and professor of medicine at Cedars-Sinai Medical Center in Los Angeles, and an Endocrine Today Editorial Board Member, told Healio. “These guidelines enable navigation of optimal therapeutic options now available for physicians and patients. Especially helpful are the evidence-based patient flow charts [that] guide the physician along a complex management path, which usually entails years or decades of follow-up.”

Shlomo Melmed

The Pituitary Society convened a consensus workshop with more than 50 academic researchers and clinical experts across five continents to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, participants reviewed data from January 2015 to April 2021 on screening and diagnosis; surgery, medical and radiation therapy; and disease-related and treatment-related complications of Cushing’s disease, all summarized in recorded lectures. The guideline includes recommendations regarding use of laboratory tests, imaging and treatment options, along with algorithms for diagnosis of Cushing’s syndrome and management of Cushing’s disease.

Updates in laboratory, testing guidance

If Cushing’s syndrome is suspected, any of the available diagnostic tests could be useful, according to the guideline. The authors recommend starting with urinary free cortisol, late-night salivary cortisol, overnight 1 mg dexamethasone suppression, or a combination, depending on local availability.

If an adrenal tumor is suspected, the guideline recommends overnight dexamethasone suppression and using late-night salivary cortisol only if cortisone concentrations can also be reported.

The guideline includes several new recommendations in the diagnosis arena, particularly on the role of salivary cortisol assays, according to Maria Fleseriu, MD, FACE, a Healio | Endocrine Today Co-editor, professor of medicine and neurological surgery and director of the Pituitary Center at Oregon Health & Science University in Portland.

Maria Fleseriu

“Salivary cortisol assays are not available in all countries, thus other screening tests can also be used,” Fleseriu told Healio. “We also highlighted the sequence of testing for recurrence, as many patients’ urinary free cortisol becomes abnormal later in the course, sometimes up to 1 year later.”

The guideline states combined biochemical and imaging for select patients could potentially replace petrosal sinus sampling, a very specialized procedure that cannot be performed in all hospitals, but more data are needed.

“With the corticotropin-releasing hormone stimulation test becoming unavailable in the U.S. and other countries, the focus is now on desmopressin to replace corticotropin-releasing hormone in some of the dynamic testing, both for diagnosis of pseudo-Cushing’s as well as localization of adrenocorticotropic hormone excess,” Fleseriu said.

The guideline also has a new recommendation for anticoagulation for high-risk patients; however, the exact duration and which patients are at higher risk remains unknown.

“We always have to balance risk for clotting with risk for bleeding postop,” Fleseriu said. “Similarly, recommended workups for bone disease and growth hormone deficiency have been further structured based on pitfalls specifically related to hypercortisolemia influencing these complications, as well as improvement after Cushing’s remission in some patients, but not all.”

New treatment options

The guideline authors recommended individualizing medical therapy for all patients with Cushing’s disease based on the clinical scenario, including severity of hypercortisolism. “Regulatory approvals, treatment availability and drug costs vary between countries and often influence treatment selection,” the authors wrote. “However, where possible, it is important to consider balancing cost of treatment with the cost and the adverse consequences of ineffective or insufficient treatment. In patients with severe disease, the primary goal is to treat aggressively to normalize cortisol concentrations.”

Fleseriu said the authors reviewed outcomes data as well as pros and cons of surgery, repeat surgery, medical treatments, radiation and bilateral adrenalectomy, highlighting the importance of individualized treatment in Cushing’s disease.

“As shown over the last few years, recurrence rates are much higher than previously thought and patients need to be followed lifelong,” Fleseriu said. “The role of adjuvant therapy after either failed pituitary surgery or recurrence is becoming more important, but preoperative or even primary medical treatment has been also used more, too, especially in the COVID-19 era.”

The guideline summarized data on all medical treatments available, either approved by regulatory agencies or used off-label, as well as drugs studied in phase 3 clinical trials.

“Based on great discussions at the meeting and subsequent emails to reach consensus, we highlighted and graded recommendations on several practical points,” Fleseriu said. “These include which factors are helpful in selection of a medical therapy, which factors are used in selecting an adrenal steroidogenesis inhibitor, how is tumor growth monitored when using an adrenal steroidogenesis inhibitor or glucocorticoid receptor blocker, and how treatment response is monitored for each therapy. We also outline which factors are considered in deciding whether to use combination therapy or to switch to another therapy and which agents are used for optimal combination therapy.”

Future research needed

The guideline authors noted more research is needed regarding screening and diagnosis of Cushing’s syndrome; researchers must optimize pituitary MRI and PET imaging using improved data acquisition and processing to improve microadenoma detection. New diagnostic algorithms are also needed for the differential diagnosis using invasive vs. noninvasive strategies. Additionally, the researchers said the use of anticoagulant prophylaxis and therapy in different populations and settings must be further studied, as well as determining the clinical benefit of restoring the circadian rhythm, potentially with a higher nighttime medication dose, as well as identifying better markers of disease activity and control.

“Hopefully, our patients will now experience a higher quality of life and fewer comorbidities if their endocrinologist and care teams are equipped with this informative roadmap for integrated management, employing a consolidation of surgery, radiation and medical treatments,” Melmed told Healio.

From https://www.healio.com/news/endocrinology/20211029/updated-cushings-disease-guideline-highlights-new-diagnosis-treatment-roadmap

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Experts offer Recommendations for Management of Pituitary Tumors

Posted on August 11, 2021 by MaryO

 

An international panel reached consensus for pre- and postoperative endocrine testing to manage adults undergoing transsphenoidal surgery, including measurement of prolactin and insulin-like growth factor I levels for all pituitary tumors.

In adults and children, transsphenoidal surgery represents the cornerstone of management for most large or functioning sellar lesions with the exception of prolactinomas, Maria Fleseriu, MD, FACE, an Endocrine Today Editorial Board Member, professor of medicine and neurological surgery and director of the Pituitary Center at Oregon Health & Science University in Portland, and colleagues wrote in Pituitary. Endocrine evaluation and management are an essential part of perioperative care; however, the details of endocrine assessment and care are not universally agreed on.

“Perioperative management of patients undergoing pituitary surgery is fascinating, as it involves many specialties — endocrinology, neurosurgery and ENT — and patients also get discharged very quickly in some countries, such as the United States,” Fleseriu told Healio. “At the start of the COVID-19 pandemic, the Physician Education Committee of the Pituitary Society, comprised of members from four continents, met to discuss a more streamlined process for workup before and after surgery for patients undergoing pituitary surgery. We have noticed big differences in management, but also some common themes, and decided to have a formal evaluation using a Delphi consensus and a much larger representation, with members from five continents.”

Building consensus

The task force behind the project, co-led by Nicholas A. Tritos, MD, DSc, associate professor of medicine at Harvard Medical School, and Pouneh K. Fazeli, MD, MPH, director of the neuroendocrinology unit and associate professor of medicine at University of Pittsburgh School of Medicine, created 35 questions and invited 55 pituitary endocrinologists to answer the questions in two Delphi rounds. Participants rated their extent of agreement with statements pertaining to perioperative endocrine evaluation and management, using a Likert-type scale.

Strong consensus, defined as at least 80% of panelists rating their agreement as 6 to 7 on a scale from 1 to 7, was achieved for 24 of 35 items. Less strict agreement, defined as ratings of 5 to 7, was reached for 31 of 35 items.

There were several significant findings, Fleseriu said.

Despite uncertainty in previous guidelines, panelists reached consensus to measure serum IGF-I for all patients with pituitary tumors preoperatively to ensure proper diagnosis of growth hormone excess, Fleseriu said.

“This is important because patients with GH-secreting adenomas do not always present with classic manifestations of acromegaly, require additional evaluation for comorbidities and postoperatively may benefit from further medical therapy or other adjuvant treatment,” Fleseriu said.

Panelists also expressed agreement on preoperative administration of glucocorticoid and thyroid hormone replacement for patients with diagnosed deficiencies, as well as perioperative use of stress-dose glucocorticoid coverage for patients with known or suspected hypoadrenalism, but not for all patients undergoing transsphenoidal surgery. Panelists also agreed on postoperative monitoring of serum sodium and cortisol and the use of desmopressin on-demand, required to control hypernatremia and/or polyuria, for patients with central diabetes insipidus.

“Agreement was achieved on postoperative monitoring of endocrine function, including morning serum cortisol in patients with Cushing’s disease, as well as serum IGF-I in patients with acromegaly,” Fleseriu said.

More research needed

Panelists did not reach consensus for a minority of items, representing areas where further research is needed, including measuring serum prolactin in dilution for all patients with large macroadenomas, Fleseriu said.

“Prolactin immunoassays can be susceptible to the ‘hook effect’ artifact, which may lead to substantial underreporting of prolactin values in sera containing very high prolactin concentrations, thus having important implications for patient management,” Fleseriu said. “Newer automated immunoassay platforms are likely to detect the hook effect; however, this may not be the case in older assays, which are still in use in many countries or laboratories. Therefore, especially when surgery is performed at an institution where automated assays are available to detect hook effect, yet patient workup has been carried out at an outside laboratory, additional lab workup might be needed. We envision this scenario can occur more often with the widespread use of telemedicine and endocrine testing being carried out at a distant laboratory.”

Additionally, there was a lack of consensus regarding preoperative testing for hypercortisolism in all patients with an apparently nonfunctioning pituitary adenoma. “This might reflect concern about false-positive results of endocrine testing in some individuals,” Fleseriu said. “On the other hand, published data suggest that some patients with Cushing’s disease may lack typical symptoms and signs and can present with an incidentally found sellar mass.”

Panelists did not reach consensus on items concerning preoperative medical therapy for patients with acromegaly or Cushing’s disease, potentially reflecting differences in practice among international centers, the clinical heterogeneity of patient populations, and ongoing uncertainties regarding the benefits of preoperative medical therapy.

“Single-center clinical experience suggests that preoperative medical therapy may be helpful in patients with Cushing’s disease and severe acute psychiatric illness or sepsis,” Fleseriu said. “Studies on acromegaly have very discordant results.

“With this study — the largest international Delphi consensus on perioperative management of patients undergoing pituitary surgery — we identified key steps in protocols which are ready to be implemented in most centers, especially for preoperative evaluation, sodium abnormalities and glucocorticoids administration postop,” Fleseriu said. “We have also highlighted several areas where need for more research is needed to optimize patients’ outcomes.”

For more information:

Maria Fleseriu, MD, FACE, can be reached at fleseriu@ohsu.edu; Twitter: @MariaFleseriu.

From https://www.healio.com/news/endocrinology/20210810/experts-offer-recommendations-for-management-of-pituitary-tumors

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Slow and Steady With Osilodrostat Best in Cushing’s Disease

Posted on May 28, 2021 by MaryO

Gradual dose escalation had fewer adverse events, same therapeutic benefit, as quicker increases

by Kristen Monaco, Staff Writer, MedPage Today May 27, 2021 A more gradual increase in oral osilodrostat (Isturisa) dosing was better tolerated among patients with Cushing’s disease, compared with those who had more accelerated increases, a researcher reported.

Looking at outcomes from two phase III trials assessing osilodrostat, only 27% of patients had hypocortisolism-related adverse events if dosing was gradually increased every 3 weeks, said Maria Fleseriu, MD, of Oregon Health & Science University in Portland, in a presentation at the virtual meeting of the American Association of Clinical Endocrinology (AACE).

On the other hand, 51% of patients experienced a hypocortisolism-related adverse event if osilodrostat dose was increased to once every 2 weeks.

Acting as a potent oral 11-beta-hydroxylase inhibitor, osilodrostat was first approved by the FDA in March 2020 for adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease. The drug is currently available in 1 mg, 5 mg, and 10 mg film-coated tablets.

The approval came based off of the positive findings from the complementary LINC3 and LINC4 trials.

The LINC3 trial included 137 adults with Cushing’s disease with a mean 24-hour urinary free cortisol concentration (mUFC) over 1.5 times the upper limit of normal (50 μg/24 hours), along with morning plasma adrenocorticotropic hormone above the lower limit of normal (9 pg/mL).

During the open-label, dose-escalation period, all the participants were given 2 mg of osilodrostat twice per day, 12 hours apart. Over this 12-week titration phase, dose escalations were allowed once every 2 weeks if there were no tolerability issues to achieve a maximum dose of 30 mg twice a day.

After this 12-week dose-escalation schedule, additional bumps up in dose were permitted every 4 weeks. The median daily osilodrostat dose was 7.1 mg.

The LINC4 trial included 73 patients with Cushing’s disease with an mUFC over 1.3 times the upper limit of normal. The 48 patients randomized to receive treatment were likewise started on 2 mg bid of osilodrostat. However, this trial had a more gradual dose-escalation schedule, as doses were increased only every 3 weeks to achieve a 20 mg bid dose.

After the 12-week dose-escalation phase, patients on a dose over 2 mg bid were restarted on 2 mg bid at week 12, where dose escalations were permitted once every 3 weeks thereafter to achieve a maximum 30 mg bid dose during this additional 36-week extension phase.

Patients in this trial achieved a median daily osilodrostat dose of 5.0 mg.

In both studies, patients’ median age was about 40 years, the majority of patients were female, and about 88% had undergone a previous pituitary surgery.

When comparing the adverse event profiles of both trials, Fleseriu and colleagues found that more than half of patients on the 2-week dose-escalation schedule experienced any grade of hypercortisolism-related adverse events. About 10.2% of these events were considered grade 3.

About 28% of these patients had adrenal insufficiency — the most common hypercortisolism-related adverse event reported. This was a catch-all term that include events like glucocorticoid deficiency, adrenocortical insufficiency, steroid withdrawal syndrome, and decreased cortisol, Fleseriu explained.

Conversely, only 27.4% of patients on a 3-week dose escalation schedule experienced a hypercortisolism-related adverse event, and only 2.7% of these were grade 3.

No grade 4 events occurred in either trial, and most events were considered mild or moderate in severity.

“These adverse events were not associated with any specific osilodrostat dose of mean UFC level,” Fleseriu said, adding that most of these events occurred during the initial dose-escalation periods.

About 60% and 58% of all hypocortisolism-related adverse events occurred during the dose titration period in the 2-week and 3-week dose-escalation schedules, respectively. These events were managed via dose reduction, a temporary interruption in medication, and/or a concomitant medication.

Very few patients in either trial permanently discontinued treatment due to these adverse events, Fleseriu noted.

“Despite differences in the frequency of dose escalation, the time to first mUFC normalization was similar in the LINC3 and LINC4 studies,” she said, adding that “gradual increases in osilodrostat dose from a starting dose of 2 mg bid can mitigate hypocortisolism-related adverse events without affecting mUFC control.”

“For patients with Cushing’s disease, osilodrostat should be initiated at the recommended starting dose with incremental dose increases, based on individual response and tolerability aimed at normalizing cortisol levels,” Fleseriu concluded.

  • Kristen Monaco is a staff writer, focusing on endocrinology, psychiatry, and dermatology news. Based out of the New York City office, she’s worked at the company for nearly five years.

Disclosures

The LINC3 and LINC4 trials were funded by Novartis.

Fleseriu reported relationships with Novartis, Recordati, and Strongbridge Biopharma.

Primary Source

American Association of Clinical Endocrinology

Source Reference: Fleseriu M, et al “Effect of dosing and titration of osilodrostat on efficacy and safety in patients with Cushing’s disease (CD): Results from two phase III trials (LINC3 and LINC4)” AACE 2021.

From https://www.medpagetoday.com/meetingcoverage/aace/92824?xid=nl_mpt_DHE_2021-05-28&eun=g1406328d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily Headlines Top Cat HeC 2021-05-28&utm_term=NL_Daily_DHE_dual-gmail-definition

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Cushing Death Rate ‘Unacceptable,’ Triple That of General Population

Posted on April 15, 2021 by MaryO

Excess mortality among people with endogenous Cushing syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.

Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality ― defined as the ratio of the number of deaths from CS divided by the total number of CS patients ― was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.

Excess deaths were higher among those with adrenal CS compared to those with Cushing disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, Leeds, United Kingdom.

“While mortality has improved since 2000, it is still significantly compromised compared to the background population…. The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.

Asked to comment, Maria Fleseriu, MD, told Medscape Medical News that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet…. This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”

She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing was unexpectedly high despite patients with adrenal cancer being excluded.”

Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, Oregon, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.

“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing treatment,” she stressed.

In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications…. We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”

Largest Study in Scale and Scope of Cushing Syndrome Mortality

Endogenous Cushing syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing syndrome). Surgery is the mainstay of initial treatment of Cushing syndrome. If an operation to remove the tumor fails to cause remission, medications are available.

Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing disease.

“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing syndrome,” Limumpornpetch noted.

The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both CS types (n = 1906).

Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15 – 7.84).

This SMR was higher among patients with adrenal Cushing syndrome (3.3) vs Cushing disease (2.8) (P = .003) and among patients who had active disease (5.7) vs those whose disease was in remission (2.3) (P < .001).

The SMR also was worse among patients with Cushing disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).

The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.

Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).

Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).

Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).

Preventing Perioperative Mortality: Consider Thromboprophylaxis

Fleseriu told Medscape Medical News that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”

Recently, Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.

The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.

“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing syndrome and balanced with individual bleeding risk,” Fleseriu advised.

A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.

Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”

Limumpornpetch has disclosed no relevant financial relationships. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.

ENDO 2021: The Endocrine Society Annual Meeting: Presented March 20, 2021

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape. Other work of hers has appeared in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She can be found on Twitter @MiriamETucker.

From https://www.medscape.com/viewarticle/949257

Filed under: adrenal, Cushing's, Endo 2021, Meetings and Conferences, pituitary, Rare Diseases, symptoms, Treatments | Tagged: , , , , , , , , , , | 1 Comment »

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