Short-Term Oral Corticosteroid Use Tied to Higher Risks of GI Bleeds, Sepsis, Heart Failure

Study Authors: Tsung-Chieh Yao, Ya-Wen Huang, et al.; Beth I. Wallace, Akbar K. Waljee

Target Audience and Goal Statement: Primary care physicians, rheumatologists, pulmonologists, dermatologists, gastroenterologists, cardiologists

The goal of this study was to examine the associations between oral corticosteroid bursts and severe adverse events among adults in Taiwan.

Question Addressed:

  • What were the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure?

Study Synopsis and Perspective:

It has long been known that long-term use of corticosteroids can be both effective and toxic. Long-term use is associated with adverse effects such as infections, GI bleeding/ulcers, cardiovascular disease (CVD), Cushing syndrome, diabetes and metabolic syndromes, cataracts, glaucoma, and osteoporosis. Most clinical practice guidelines caution against long-term steroid use unless medically necessary.

Action Points

  • In a retrospective cohort study and self-controlled case series, prescriptions for oral steroid bursts were found to be associated with increased risks for gastrointestinal bleeding, sepsis, and heart failure within the first month after initiation, despite a median exposure of just 3 days.
  • Note that the risks were highest 5 to 30 days after exposure, and attenuated during the subsequent 31 to 90 days.

Instead, clinical practice guidelines recommend steroid bursts for inflammatory ailments such as asthma, inflammatory bowel disease, and rheumatoid arthritis. Waljee and colleagues noted in 2017 that they are most commonly used for upper respiratory infections, suggesting that many people are receiving steroids in the real world.

In a retrospective cohort study and self-controlled case series, prescriptions for oral steroid bursts — defined as short courses of oral corticosteroids for 14 or fewer days — were found to be associated with increased risks for GI bleeding, sepsis, and heart failure within the first month after initiation, despite a median exposure of just 3 days, according to Tsung-Chieh Yao, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, and colleagues.

The risks were highest 5 to 30 days after exposure, and attenuated during the subsequent 31 to 90 days, they reported in Annals of Internal Medicine.

The self-controlled case series was based on national medical claims records. Included were adults, ages 20-64, covered by Taiwan’s National Health Insurance in 2013-2015.

Out of a population of more than 15.8 million, study authors identified 2,623,327 people who received a steroid burst during the study period. These individuals were age 38 on average, and 55.3% were women. About 85% had no baseline comorbid conditions.

The most common indications for the steroid burst were skin disorders and respiratory tract infections.

The incidence rates among patients prescribed steroid bursts were 27.1 per 1,000 person-years for GI bleeding (incidence rate ratio [IRR] 1.80, 95% CI 1.75-1.84), 1.5 per 1,000 person-years for sepsis (IRR 1.99, 95% CI 1.70-2.32), and 1.3 per 1,000 person-years for heart failure (IRR 2.37, 95% CI 2.13-2.63).

Absolute risk elevations were similar in patients with and without comorbid conditions, meaning that the potential for harm was not limited to those at high risk for these adverse events.

The study authors acknowledged that they could not adjust for disease severity and major lifestyle factors such as alcohol use, smoking, and body mass index; because these factors were static, the effect could be eliminated using the self-controlled case series design. Their reliance on prescription data also meant they could not tell if patients actually complied with oral corticosteroid therapy. Furthermore, the exclusion of the elderly and younger populations also left room for underestimation of the risks of steroid bursts, they said.

Source References: Annals of Internal Medicine 2020; DOI: 10.7326/M20-0432

Editorial: Annals of Internal Medicine 2020; DOI: 10.7326/M20-4234

Study Highlights and Explanation of Findings:

Over the 3-year study period, steroid bursts were commonly prescribed to adults. Such prescriptions were written for common conditions, including skin disorders and upper respiratory tract infections. The highest risks for GI bleeding, sepsis, and heart failure occurred within the first month after receipt of the steroid burst, and this risk was attenuated during the subsequent 31 to 90 days.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the researchers wrote. Notably, one corticosteroid that fits the bill is dexamethasone — a medication that holds promise for the treatment of critically ill COVID-19 patients, although it is not generally prescribed orally for these patients.

Based on preliminary results, the NIH’s COVID-19 treatment guidelines panel recommended the use of “dexamethasone (at a dose of 6 mg per day for up to 10 days) in patients with COVID-19 who are mechanically ventilated and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated.” In addition, they recommend “against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen.”

“We are now learning that bursts as short as 3 days may increase risk for serious AEs [adverse events], even in young and healthy people. As providers, we must reflect on how and why we prescribe corticosteroids to develop strategies that prevent avoidable harms,” wrote Beth Wallace, MD, and Akbar Waljee, MD, both of the VA Ann Arbor Healthcare System and Michigan Medicine.

On the basis of the reported risk differences in the study, Wallace and Waljee calculated that one million patients exposed to corticosteroid bursts experienced 41,200 GI bleeding events, 400 cases of sepsis, and 4,000 cases of new heart failure per year that were directly attributed to this brief treatment.

“Although many providers already avoid corticosteroids in elderly patients and those with comorbid conditions, prescribing short bursts to ‘low-risk’ patients has generally been viewed as innocuous, even in cases where the benefit is unclear. However, Yao and colleagues provide evidence that this practice may risk serious harm, making it difficult to justify in cases where corticosteroid use lacks evidence of meaningful benefit,” they wrote in an accompanying editorial.

“Medication-related risks for AEs can, of course, be outweighed by major treatment benefit. However, this study and prior work show that corticosteroid bursts are frequently prescribed for self-limited conditions, where evidence of benefit is lacking,” Wallace and Waljee noted.

“As we reflect on how to respond to these findings, it is useful to note the many parallels between use of corticosteroid bursts and that of other short-term medications, such as antibiotics and opiates. All of these treatments have well-defined indications but can cause net harm when used — as they frequently are — when evidence of benefit is low,” they emphasized.

Last Updated August 07, 2020
Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine (Retired), Harvard Medical School, Boston

From https://www.medpagetoday.org/primarycare/generalprimarycare/87959?xid=nl_mpt_DHE_2020-08-08&eun=g1406328d0r&utm_term=NL_Daily_DHE_dual-gmail-definition&vpass=1

Endocrine Society experts call for expanded screening for primary aldosteronism

Washington, DC–The Endocrine Society today issued a Clinical Practice Guideline calling on physicians to ramp up screening for primary aldosteronism, a common cause of high blood pressure.

People with primary aldosteronism face a higher risk of developing cardiovascular disease and dying from it than other people with high blood pressure. As many as one in ten people with high blood pressure may have primary aldosteronism. Uncontrolled high blood pressure can put these individuals at risk for stroke, heart attack, heart failure or kidney failure.

The guideline, entitled “The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline,” was published online and will appear in the May 2016 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society. The guideline updates recommendations from the Society’s 2008 guideline on primary aldosteronism.

“In the past eight years, we have come to recognize that primary aldosteronism, despite being quite common, frequently goes undiagnosed and untreated,” said John W. Funder, MD, PhD, of the Hudson Institute of Medical Research in Clayton, Australia, and chair of the task force that authored the guideline. “This is a major public health issue. Many people with primary aldosteronism are never screened due to the associated costs. Better screening processes are needed to ensure no person suffering from primary aldosteronism and the resulting risks of uncontrolled high blood pressure goes untreated.”

Primary aldosteronism occurs when the adrenal glands — the small glands located on the top of each kidney – produce too much of the hormone aldosterone. This causes aldosterone, which helps balance levels of sodium and potassium, to build up in the body. The resulting excess sodium can lead to a rise in blood pressure.

The Endocrine Society recommends primary aldosterone screening for people who meet one of the following criteria:

  • Those who have sustained blood pressure above 150/100 in three separate measurements taken on different days;
  • People who have hypertension resistant to three conventional antihypertensive drugs;
  • People whose hypertension is controlled with four or more medications;
  • People with hypertension and low levels of potassium in the blood;
  • Those who have hypertension and a mass on the adrenal gland called an adrenal incidentaloma;
  • People with both hypertension and sleep apnea;
  • People with hypertension and a family history of early-onset hypertension or stroke before age 40; and
  • All hypertensive first-degree relatives of patients with primary aldosteronism.

Other recommendations from the guideline include:

  • The plasma aldosterone-to-renin ratio (ARR) test should be used to screen for primary aldosteronism.
  • All patients diagnosed with primary aldosteronism should undergo a CT scan of the adrenal glands to screen for a rare cancer called adrenocortical carcinoma.
  • When patients choose to treat the condition by having one adrenal gland surgically removed, an experienced radiologist should take blood samples from each adrenal vein and have them analyzed. This procedure, called adrenal vein sampling, is the gold standard for determining whether one or both adrenal glands is producing excess aldosterone.
  • For people with primary aldosteronism caused by overactivity in one adrenal gland, the recommended course of treatment is minimally invasive surgery to remove that adrenal gland.
  • For patients who are unable or unwilling to have surgery, medical treatment including a mineralocorticoid receptor (MR) agonist is the preferred treatment option.

###

The Hormone Health Network offers resources on primary aldosteronism athttp://www.hormone.org/questions-and-answers/2012/primary-aldosteronism.

Other members of the Endocrine Society task force that developed this guideline include: Robert M. Carey, of the University of Virginia Health System in Charlottesville, VA; Franco Mantero of the University of Padova in Padua, Italy; M. Hassan Murad of the Mayo Clinic in Rochester, MN; Martin Reincke of the Klinikum of the Ludwig-Maximilians-University of Munich in München, Bavaria, Germany; Hirotaka Shibata of Oita University in Oita, Japan; Michael Stowasser of the University of Queensland in Brisbane, Australia; and William F. Young, Jr. of the Mayo Clinic in Rochester, MN.

The Society established the Clinical Practice Guideline Program to provide endocrinologists and other clinicians with evidence-based recommendations in the diagnosis and treatment of endocrine-related conditions. Each guideline is created by a task force of topic-related experts in the field. Task forces rely on evidence-based reviews of the literature in the development of guideline recommendations. The Endocrine Society does not solicit or accept corporate support for its guidelines. All Clinical Practice Guidelines are supported entirely by Society funds.

The Clinical Practice Guideline was co-sponsored by the American Heart Association, the American Association of Endocrine Surgeons, the European Society of Endocrinology, the European Society of Hypertension, the International Association of Endocrine Surgeons, the International Society of Hypertension, the Japan Endocrine Society and The Japanese Society of Hypertension.

The guideline was published online at http://press.endocrine.org/doi/10.1210/jc.2015-4061, ahead of print.

Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

The Society, which is celebrating its centennial in 2016, has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at http://www.endocrine.org. Follow us on Twitter at @TheEndoSociety and @EndoMedia.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

From http://www.eurekalert.org/pub_releases/2016-04/tes-ese042616.php

If One Partner Has Cushing’s Syndrome, Can The Couple Still Get Pregnant?

Cushing’s syndrome can affect fertility in both men and women.

Women

The high levels of cortisol in Cushing’s syndrome disrupt a woman’s ovaries. Her menstrual periods may stop completely or become irregular. As a result, women with Cushing’s syndrome almost always have difficulty becoming pregnant.5,6,7 For those who do become pregnant, the risk of miscarriage is high.5,6,7

In rare cases, usually when a woman’s Cushing’s syndrome is caused by a benign adrenal tumor, pregnancy can occur, but it brings high risk for the mother and fetus.5,6,7

After a woman is treated for Cushing’s syndrome, her ovaries often recover from the effects of too much cortisol. Her regular menstrual cycles will return, and she can become pregnant.8

In some women, regular periods do not return after they are treated for Cushing’s syndrome. This occurs if surgery removes the part of the pituitary gland involved in reproduction.4 An infertility specialist can prescribe hormone therapy to bring back regular periods, ovulation, and fertility.8

Men

A man diagnosed with Cushing’s syndrome may have a decline in sperm production and could have reduced fertility.9 He also might experience a lowered sex drive as well as impotence (pronounced IM-puh-tuhns). In addition, some medications used to treat Cushing’s syndrome can reduce fertility.10 However, fertility usually recovers after Cushing’s syndrome is cured and treatment has stopped.9

Does Cushing’s syndrome affect pregnancy?

Cushing’s syndrome can cause serious and potentially life-threatening effects for the mother and the fetus during pregnancy.11,12 For example, Cushing’s syndrome raises a woman’s risk of developing pregnancy-related high blood pressure (called preeclampsia, pronounced pree-i-KLAMP-see-uh, or eclampsia) and/or pregnancy diabetes, which also is called gestational (pronounced je-STEY-shuhn-ul) diabetes). Infection and slow healing of any wounds are more likely, as is heart failure. When the syndrome is caused by a tumor, it will be surgically removed as early as possible to reduce any threat.13


  1. Margulies, P. (n.d.). Adrenal diseases—Cushing’s syndrome: The facts you need to know. Retrieved May 21, 2012, from National Adrenal Diseases Foundation website http://www.nadf.us/adrenal-diseases/cushings-syndrome/ External Web Site Policy
  2. Nieman, L. K., & Ilias, I. (2005). Evaluation and treatment of Cushing’s syndrome. Journal of American Medicine, 118(12), 1340-1346. PMID 16378774.
  3. American Cancer Society. (n.d.). Fact sheet on pituitary tumors. Retrieved May 19, 2012, fromhttp://documents.cancer.org/acs/groups/cid/documents/webcontent/003133-pdf.pdf (PDF – 171 KB). External Web Site Policy
  4. Biddie, S. C., Conway-Campbell, B. L, & Lightman, S. L. (2012). Dynamic regulation of glucocorticoid signalling in health and disease. Rheumatology, 51(3), 4034-4112. Retrieved May 19, 2012, from PMID: 3281495.
  5. Abraham, M. R., & Smith, C. V. (n.d.). Adrenal disease and pregnancy.Retrieved April 8, 2012, fromhttp://emedicine.medscape.com/article/127772-overview – aw2aab6b6. External Web Site Policy
  6. Pickard, J., Jochen, A. L., Sadur, C. N., & Hofeldt, F. D. (1990). Cushing’s syndrome in pregnancy. Obstetrical & Gynecological Survey, 45(2), 87-93.PMID 2405312.
  7. Lindsay, J. R., Jonklaas, J., Oldfield, E. H., & Nieman, L. K. (2005). Cushing’s syndrome during pregnancy: Personal experience and review of the literature. Journal of Clinical Endocrinology and Metabolism, 90(5), 3077.PMID 15705919.
  8. Klibansky, A. (n.d.). Pregnancy after cure of Cushing’s disease. Retrieved April 27, 2012, fromhttp://03342db.netsolhost.com/page/pregnancy_after_cure_of_cushings_disease.php. External Web Site Policy
  9. Jequier, A.M. Endocrine infertility. In Male infertility: A clinical guide (2nd ed.). Cambridge University Press, 2011: chap 20, pages 187-188. Retrieved May 19, 2012, from http://books.google.com/books?id=DQL0YC79uCMC&pg=PA188&lpg=PA188&dq=male+infertility+causes+and+treatment+Cushing&source=bl&ots=k1Ah5tVJC7&sig=WJR4N0wUawlh0Rant31QMPq6ufs&hl=en&sa=X&ei=hGe5T-LrHYSX6AHgrvmzCw&ved=0CGoQ6AEwAQ#v=onepage&q=male%20infertility%20causes%20and%20treatment%20Cushing&f=false. External Web Site Policy
  10. Stewart, P. M., & Krone, N. P. (2011). The adrenal cortex. In Kronenberg, H. M., Shlomo, M., Polonsky, K. S., Larsen P. R. (Eds.). Williams textbook of endocrinology (12th ed.). (chap. 15). Philadelphia, PA: Saunders Elsevier.
  11. Abraham, M. R., & Smith, C. V. Adrenal disease and pregnancy. Retrieved April 8, 2012, from http://emedicine.medscape.com/article/127772-overview – aw2aab6b6. External Web Site Policy
  12. Buescher, M. A. (1996). Cushing’s syndrome in pregnancy. Endocrinologist, 6, 357-361.
  13. Ezzat, S., Asa, S. L., Couldwell, W. T., Barr, C. E., Dodge, W. E., Vance M. L., et al. (2004). The prevalence of pituitary adenomas: A systematic review.Cancer, 101(3), 613-619. PMID 15274075.

From https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/faqs.aspx

<span>%d</span> bloggers like this: