Patients on Steroids With COVID-19 Might Need Rescue Steroids

Posted on April 6, 2020 by MaryO

 

Endocrinologists have underlined the importance that physicians consider “a stress dose” of glucocorticoids in the event of severe COVID-19 infection in endocrine, and other, patients on long-term steroids.

 

People taking corticosteroids on a routine basis for a variety of underlying inflammatory conditions, such as asthma, allergies, and arthritis, are at elevated risk of being infected with, and adversely affected by, COVID-19.

 

This also applies to a rarer group of patients with adrenal insufficiency and uncontrolled Cushing syndrome, as well as secondary adrenal insufficiency occurring in hypopituitarism, who also rely on glucocorticoids for day-to-day living.

 

In the event of COVID-19, all of these individuals may be unable to mount a normal stress response, and “in the case of adrenal suppression…such patients may run into severe difficulties, particularly if on intensive care units,” warns Paul Stewart, MD, University of Leeds, UK, and editor-in-chief of the Journal of Clinical Endocrinology & Metabolism (JCEM).

 

As such, it is vitally important to recognize that “Injectable supplemental glucocorticoid therapy in this setting can reverse the risk of potentially fatal adrenal failure and should be considered in every case,” Stewart and colleagues emphasize in a newly published editorial in JCEM.

 

They note this advice must be considered alongside World Health Organization (WHO) guidance against prescribing therapeutic glucocorticoids to treat complications of COVID-19, based on prior experience in patients with acute respiratory distress syndrome, as well as those affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).

 

The key difference here is not to use pharmacologic doses of glucocorticoids as treatment for COVID-19 (where they have no effect), but rather to prevent death from adrenal failure by using “stress” doses of replacement glucocorticoid, Stewart explained to Medscape Medical News.

 

“No patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months)…should die without consideration” for a stress dose of replacement glucocorticoid therapy.

“The intent here is to ensure that no patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months) by whatever route should die without consideration for parenteral glucocorticoid therapy,” the editorialists write.

 

He advises using physiological stress doses of hydrocortisone (50-100 mg intravenously tid).

 

Specific Advice for Adrenal Insufficiency: Follow Sick Day Rules

 

A separate statement by the American Association of Clinical Endocrinologists (AACE) also emphasizes that it is particularly important for patients with adrenal insufficiency to follow advice from the Centers for Disease Control and Prevention (CDC) or similar guidance on preventing COVID-19 infection, including social distancing and frequent hand washing.

 

Such patients should continue to take medications as prescribed and ensure they have appropriate supplies of oral and injectable steroids, ideally for 90 days, AACE advises.

And if there is a shortage of hydrocortisone, the statement advises patients ask a pharmacist or physician about replacement hydrocortisone with different doses that might be available.

Stewart agrees that patients with adrenal insufficiency need to be hypervigilant, but says that “if they do become ill, for the most part they are well counseled to respond appropriately to intercurrent infections.”

Nevertheless, it is “invaluable to reiterate ‘sick day rules'” for suspected COVID-19 infection.

“Any patient who develops a dry continuous cough and fever should immediately double their daily oral glucocorticoid dose and continue on this regimen until the fever has subsided.”

If a patient still deteriorates on this regimen, develops diarrhea or vomiting, or is unable to take oral glucocorticoids for other reasons, they should contact their physicians or seek urgent medical care to receive parenteral treatment with a glucocorticoid.

J Clin Endocrinol Metab. Published online March 31, 2020. Position statement

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From https://www.medscape.com/viewarticle/928072?nlid=134869_3901&src=wnl_newsalrt_200404_MSCPEDIT&uac=295048SY&impID=2335560&faf=1&fbclid=IwAR1zZe6fqDS3tKuHUYoFpbvBMkQYJ4JN59RzC93xdzVcGGkJIz5bnmmE4LY

Filed under: adrenal crisis, Cushing's, General Health, Treatments | Leave a comment »

AACE Position Statement: Coronavirus (COVID-19) and People with Adrenal Insufficiency and Cushing’s Syndrome

Posted on March 31, 2020 by MaryO

With the novel COVID-19 virus continuing to spread, it is crucial to adhere to the advice from experts and the Centers for Disease Control and Prevention (CDC) to help reduce risk of infection for individuals and the population at large. This is particularly important for people with adrenal insufficiency and people with uncontrolled Cushing’s Syndrome.

Studies have reported that individuals with adrenal insufficiency have an increased rate of respiratory infection-related deaths, possibly due to impaired immune function. As such, people with adrenal insufficiency should observe the following recommendations:

  • Maintain social distancing to reduce the risk of contracting COVID-19
  • Continue taking medications as prescribed
  • Ensure appropriate supplies for oral and injectable steroids at home, ideally a 90-day preparation
    • In the case of hydrocortisone shortages, ask your pharmacist and physician about replacement with different strengths of hydrocortisone tablets that might be available. Hydrocortisone (or brand name Cortef) tablets have 5 mg, 10 mg or 20 mg strength
  • In cases of acute illness, increase the hydrocortisone dose per instructions and call the physician’s office for more details
    • Follow sick day rules for increasing oral glucocorticoids or injectables per your physician’s recommendations
      • In general, patients should double their usual glucocorticoid dose in times of acute illness
      • In case of inability to take oral glucocorticoids, contact your physician for alternative medicines and regimens
  • If experiencing fever, cough, shortness of breath or other symptoms, call both the COVID-19 hotline (check your state government website for contact information) and your primary care physician or endocrinologist
  • Monitor symptoms and contact your physician immediately following signs of illness
  • Acquire a medical alert bracelet/necklace in case of an emergency

Individuals with uncontrolled Cushing’s Syndrome of any origin are at higher risk of infection in general. Although information on people with Cushing’s Syndrome and COVID-19 is scarce, given the rarity of the condition, those with Cushing’s Syndrome should strictly adhere to CDC recommendations:

  • Maintain social distancing to reduce the risk of contracting COVID-19
  • If experiencing fever, cough, shortness of breath or other symptoms, call both the COVID-19 hotline (check your state government website for contact information) and your primary care physician or endocrinologist

In addition, people with either condition should continue to follow the general guidelines at these times:

  • Stay home as much as possible to reduce your risk of being exposed
    • When you do go out in public, avoid crowds and limit close contact with others
    • Avoid non-essential travel
  • Wash your hands with soap and water regularly, for at least 20 seconds, especially before eating or drinking and after using the restroom and blowing your nose, coughing or sneezing
  • If soap and water are not readily available, use an alcohol-based sanitizer with at least 60% alcohol
  • Cover your nose and mouth when coughing or sneezing with a tissue or a flexed elbow, then throw the tissue in the trash
  • Avoid touching your eyes, mouth or nose when possible

From https://www.aace.com/recent-news-and-updates/aace-position-statement-coronavirus-covid-19-and-people-adrenal

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FDA Approves New Treatment for Adults with Cushing’s Disease

Posted on March 9, 2020 by MaryO

The U.S. Food and Drug Administration today approved Isturisa (osilodrostat) oral tablets for adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease. Cushing’s disease is a rare disease in which the adrenal glands make too much of the cortisol hormone. Isturisa is the first FDA-approved drug to directly address this cortisol overproduction by blocking the enzyme known as 11-beta-hydroxylase and preventing cortisol synthesis.

“The FDA supports the development of safe and effective treatments for rare diseases, and this new therapy can help people with Cushing’s disease, a rare condition where excessive cortisol production puts them at risk for other medical issues,” said Mary Thanh Hai, M.D., acting director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “By helping patients achieve normal cortisol levels, this medication is an important treatment option for adults with Cushing’s disease.”

Cushing’s disease is caused by a pituitary tumor that releases too much of a hormone called adrenocorticotropin, which stimulates the adrenal gland to produce an excessive amount of cortisol. The disease is most common among adults between the ages of 30 to 50, and it affects women three times more often than men. Cushing’s disease can cause significant health issues, such as high blood pressure, obesity, type 2 diabetes, blood clots in the legs and lungs, bone loss and fractures, a weakened immune system and depression. Patients may have thin arms and legs, a round red full face, increased fat around the neck, easy bruising, striae (purple stretch marks) and weak muscles.

Isturisa’s safety and effectiveness for treating Cushing’s disease among adults was evaluated in a study of 137 adult patients (about three-quarters women) with a mean age of 41 years. The majority of patients either had undergone pituitary surgery that did not cure Cushing’s disease or were not surgical candidates. In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 milligrams (mg) of Isturisa twice a day that could be increased every two weeks up to 30 mg twice a day. At the end of this 24-week period, about half of patients had cortisol levels within normal limits. After this point, 71 patients who did not need further dose increases and tolerated the drug for the last 12 weeks entered an eight-week, double-blind, randomized withdrawal study where they either received Isturisa or a placebo (inactive treatment). At the end of this withdrawal period, 86% of patients receiving Isturisa maintained cortisol levels within normal limits compared to 30% of patients taking the placebo.

The most common side effects reported in the clinical trial for Isturisa were adrenal insufficiency, headache, vomiting, nausea, fatigue and edema (swelling caused by fluid retention). Hypocortisolism (low cortisol levels), QTc prolongation (a heart rhythm condition) and elevations in adrenal hormone precursors (inactive substance converted into a hormone) and androgens (hormone that regulates male characteristics) may also occur in people taking Isturisa.

Isturisa is taken by mouth twice a day, in the morning and evening as directed by a health care provider. After treatment has started, a provider may re-evaluate dosage, depending upon the patient’s response.

Isturisa received Orphan Drug Designation, which is a special status granted to a drug intended to treat a rare disease or condition.

The FDA granted the approval of Isturisa to Novartis.

Media Contact: Monique Richards, 240-402-3014
Consumer Inquiries: Email, 888-INFO-FDA

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

SOURCE U.S. Food and Drug Administration

Related Links

http://www.fda.gov

From https://www.prnewswire.com/news-releases/fda-approves-new-treatment-for-adults-with-cushings-disease-301019293.html

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Risk for thrombotic events high after Cushing’s syndrome surgery

Posted on December 31, 2019 by MaryO

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

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Cushing’s Disease—Monthly Injection Is Good Alternative to Surgery

Posted on October 1, 2019 by MaryO

Written by Kathleen Doheny with Maria Fleseriu, MD, FACE, and Vivien Herman-Bonert, MD

Cushing’s disease, an uncommon but hard to treat endocrine disorder, occurs when a tumor on the pituitary gland, called an adenoma—that is almost always benign—leads to an overproduction of ACTH (adrenocorticotropic hormone), which is responsible for stimulating the release of cortisol, also known as the stress hormone.

Until now, surgery to remove the non-cancerous but problematic tumor has been the only effective treatment. Still, many patients will require medication to help control their serum cortisol levels, and others cannot have surgery or would prefer to avoid it.

Finally, a drug proves effective as added on or alternative to surgery in managing Cushing’s disease. Photo; 123rf

New Drug Offers Alternative to Surgery for Cushing’s Disease

Now, there is good news about long-term positive results achieved with pasireotide (Signifor)—the first medication to demonstrate effectiveness in both normalizing serum cortisol levels and either shrinking or slowing growth of tumors over the long term.1,2  These findings appear in the journal, Clinical Endocrinology, showing that patients followed for 36 months as part of an ongoing study had improved patient outcomes for Cushing’s disease.2

“What we knew before this extension study was—the drug will work in approximately half of the patients with mild Cushing’s disease,” says study author Maria Fleseriu, MD, FACE, director of the Northwest Pituitary Center and professor of neurological surgery and medicine in the division of endocrinology, diabetes and clinical nutrition at the Oregon Health and Sciences University School of Medicine.

“Pasireotide also offers good clinical benefits,” says Dr. Fleseriu who is also the president of the Pituitary Society, “which includes improvements in blood pressure, other signs and symptoms of Cushing’s symptom], and quality of life.”2

What Symptoms Are Helped by Drug for Cushing’s Disease?  

Among the signs and symptoms of Cushing’s disease that are lessened with treatment are:3

  • Changes in physical appearance such as wide, purple stretch marks on the skin (eg, chest, armpits, abdomen, thighs)
  • Rapid and unexplained weight gain
  • A more full, rounder face
  • Protruding abdomen from fat deposits
  • Increased fat deposits around the neck area

The accumulation of adipose tissue raises the risk of heart disease, which adds to the urgency of effective treatment. In addition, many individuals who have Cushing’s disease also complain of quality of life issues such as fatigue, depression, mood and behavioral problems, as well as poor memory.2

As good as the results appear following the longer term use of pasireotide,2 Dr. Fleseriu admits that in any extension study in which patients are asked to continue on, there are some built-in limitations, which may influence the findings. For example, patients who agree to stay on do so because they are good responders, meaning they feel better, so they’re happy to stick with the study.

“Fortunately, for the patients who have responded to pasireotide initially, this is a drug that can be  continued as there are no new safety signals with longer use,” Dr. Fleseriu tells EndocrineWeb, “and when the response at the start is good, very few patients will lose control of their urinary free cortisol over time. That’s a frequent marker used to monitor patient’s status. For those patients with large tumors, almost half of them had a significant shrinkage, and all the others had a stable tumor size.”

What Are the Reasons to Consider Drug Treatment to Manage Cushing’s Symptoms

The extension study ”was important because we didn’t have any long-term data regarding patient response to this once-a-month treatment to manage Cushing’s disease,” she says.

While selective surgical removal of the tumor is the preferred treatment choice, the success rate in patients varies, and Cushing’s symptoms persist in up to 35% of patients after surgery. In addition, recurrent rates (ie, return of disease) range from 13% to 66% after individuals experience different durations remaining in remission.1

Therefore, the availability of an effective, long-lasting drug will change the course of therapy for many patients with Cushing’s disease going forward. Not only will pasireotide benefit patients who have persistent and recurrent disease after undergoing surgery, but also this medication will be beneficial for those who are not candidates for surgery or just wish to avoid having this procedure, he said.

Examining the Safety and Tolerability of Pasireotide  

This long-acting therapy, pasireotide, which is given by injection, was approved in the US after reviewing results of a 12-month Phase 3 trial.1  In the initial study, participants had a confirmed pituitary cause of the Cushing’s disease. After that, the researchers added the optional 12-month open-label, extension study, and now patients can continue on in a separate long-term safety study.

Those eligible for the 12-month extension had to have mean urinary free cortisol not exceeding the upper limit of normal (166.5 nanomoles per 24 hour) and/or be considered by the investigator to be getting substantial clinical benefit from treatment with long-action pasireotide, and to demonstrate tolerability of pasireotide during the core study.1

Of the 150 in the initial trial, 81 participants, or 54% of the patients, entered the extension study. Of those, 39 completed the next phase, and most also enrolled in another long-term safety study—these results not yet available).2

During the core study, 1 participants were randomly assigned to 10 or 30 mg of the drug every 28 days, with doses based on effectiveness and tolerability. When they entered the extension, patients were given the same dose they received at month.1,2

Study Outcomes Offer Advantages in Cushing’s Disease

Of those who received 36 months of treatment with pasireotide, nearly three in four (72.2%) had controlled levels of urinary free cortisol at this time point.2 Equally good news for this drug was that tumors either shrank or did not grow. Of those individuals who started the trial with a measurable tumor (adenoma) as well as those with an adenoma at the two year mark (35 people), 85.7% of them experienced a reduction of 20% or more or less than a 20% change in tumor volume. No  macroadenomas present at the start of the study showed a change of more than 20% at either month 24 or 36.2

Improvements in blood pressure, body mass index (BMI) and waist circumference continued throughout the extension study.1  Those factors influence CVD risk, the leading cause of death in those with Cushing’s.4

As for adverse events, most of the study participants, 91.4%, did report one or more complaint during the extension study—most commonly, it was high blood sugar, which was reported by nearly 40% of participants.2. This is not surprising when you consider that most (81.5%) of the individuals participating in the extension trial entered with a diagnosis of diabetes or use of antidiabetic medication, and even more of them (88.9%) had diabetes at the last evaluation.1  

This complication indicates the need for people with Cushing’s disease to check their blood glucose, as appropriate.

Do You Have Cushing’s Disese [sic]? Here’s What You Need to Know 

Women typically develop Cushing’s disease more often than men.

What else should you be aware of if you and your doctor decide this medication will help you? Monitoring is crucial, says Dr. Fleseriu, as you will need to have your cortisol levels checked, and you should be on alert for any diabetes signals, which will require close monitoring and regular follow-up for disease management.

Another understanding gained from the results of this drug study: “This medication works on the tumor level,” she says. “If the patient has a macroadenoma (large tumor), this would be the preferred treatment.” However, it should be used with caution in those with diabetes given the increased risk of experiencing high blood sugar.

The researchers conclude that “the long-term safety profile of pasireotide was very favorable and consistent with that reported during the first 12 months of treatment. These data support the use of long-acting pasireotide as an effective long-term treatment option for some patients with Cushing’s Disease.”1

Understanding Benefits of New Drug to Treat Cushing’s Diseease [sic]

Vivien S. Herman-Bonert, MD, an endocrinologist and clinical director of the Pituitary Center at Cedars-Sinai Medical Center in Los Angeles, agreed to discuss the study findings, after agreeing to review the research for EndocrineWeb.

As to who might benefit most from monthly pasireotide injections? Dr. Herman-Bonert says, “any patient with Cushing’s disease that requires long-term medical therapy, which includes patients with persistent or recurrent disease after surgery.” Certainly, anyone who has had poor response to any other medical therapies for Cushing’s disease either because they didn’t work well enough or because the side effects were too much, will likely benefit a well, she adds.

Among the pluses that came out of the study, she says, is that nearly half of the patients had controlled average urinary free cortisol levels after two full years, and 72% of the participants who continued on with the drug for 36 months were able to remain in good urinary cortisol control .1

As the authors stated, tumor shrinkage was another clear benefit of taking long-term pasireotide. That makes the drug a potentially good choice for those even with large tumors or with progressive tumor growth, she says. It’s always good for anyone with Cushing’s disease to have an alterative [sic] to surgery, or a back-up option when surgery isn’t quite enough, says Dr. Herman-Bonert.

The best news for patients is that quality of life scores improved,1 she adds.

Dr Herman-Bonert did add a note of caution: Although the treatment in this study is described as ”long-term, patients will need to be on this for far longer than 2 to 3 years,” she says. So, the data reported in this study may or may not persist, and we don’t yet know what the impact will be 10 or 25 years out.

Also, the issue of hyperglycemia-related adverse events raises a concern, given the vast majority (81%) of patients who have both Cushing’s disease and diabetes. Most of those taking this drug had a dual diagnosis—having diabetes, a history of diabetes, or taking antidiabetic medicine.

If you are under care for diabetes and you require treatment for Cushing’s disease, you must be ver mindful that taking pasireotide will likely lead to high blood sugar spikes, so you should plan to address this with your healthcare provider.

 

Dr. Fleseriu reports research support paid to Oregon Health & Science University from Novartis and other 0companies and consultancy fees from Novartis and Strongbridge Biopharma. Dr. Herman-Bonert has no relevant disclosures.

The study was underwritten by Novartis Pharma AG, the drug maker. 

From https://www.endocrineweb.com/news/pituitary-disorders/62449-cushings-disease-monthly-injection-good-alternative-surgery

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