Cushing’s Syndrome Presenting as Non-Atherosclerotic Myocardial Infarction and Heart Failure

Posted on November 6, 2023 by MaryO

Abstract

Cushing’s syndrome is a rare cause of myocardial infarction and heart failure. Herein, we report a female patient who presented acute myocardial infarction and heart failure with reduced ejection fraction. The patient was found to have hypercortisolism secondary to adrenocortical adenoma and responded well to therapy. This case underlines the effects of hypercortisolism on the cardiovascular system. The clinical presentation of this patient is unique because non-atherosclerotic myocardial infarction is rarely reported in Cushing’s syndrome patients.

Introduction

Cushing’s syndrome is an endocrine condition associated with excessive secretion of cortisol. Hypertension, vascular atherosclerosis, and chronic cardiac remodelling and dysfunction are commonly recognized cardiovascular complications in Cushing’s syndrome patients.1 Herein, we report a rare case of Cushing’s syndrome patient with a primary diagnosis of non-atherosclerotic myocardial infarction and heart failure (HF).

Case Report

A 61-year-old female with a past medical history of chronic obstructive pulmonary disease was admitted with sudden onset chest pain on 6 February 2018. Electrocardiogram showed ST-segment elevation in leads V3–V5. Blood biochemical results of 1 h after the onset of chest pain: cardiac troponin I (cTnI) 0.06 ug/L↑, creatine kinase (CK) 63 U/L, creatine phosphokinase-MB (CK-MB) 22 U/L, aspartate transferase (AST) 19 U/L, and lactic dehydrogenase (LDH) 482 U/L. Myocardial injury markers were markedly elevated at the time point of 18 h after onset: cTnI 13.9 ug/L↑, CK 613 U/L↑, CK-MB 102 U/L↑, AST 112 U/L↑, and LDH 833 U/L↑. Due to the acute ECG changes and elevated myocardial injury markers, the patient was preliminarily diagnosed as ST-segment elevation myocardial infarction (STEMI) and underwent coronary angiography, which showed no stenosis, occlusion or dissection of coronary arteries (Figure 1). Echocardiography showed enlarged left atrial dimension (LAD, 55 mm) and left ventricular end diastolic dimension (LVDd, 57 mm), and reduced ejection fraction (EF, 33%). The patient was treated for STEMI and HF, and was started on aspirin, statin, diuretic of furosemide and spirolactone, metoprolol, and Sacubitril/valsartan (SV, initiated June, 2020). The patient was strictly adherent to the medication prescribed (Table 1).

Details are in the caption following the image

Coronary angiogram demonstrating no significant obstruction in coronary artery circulation.
Table 1. Echocardiography results
2020-06-22 2020-09-02 2021-03-29 2021-06-02 2021-09-01 2021-10-22 2021-12-21
LAD (mm) 55 55 46 52 47 44 41
LVDd (mm) 57 57 53 55 54 51 55
IVS (mm) 10 10 11 10 10 10 11
LVPW (mm) 11 11 11 10 11 9 10
EF (%) 33 30 31 39 47 49 52.5
  • EF, ejection fraction; IVS, interventricular septum; LAD, left atrium dimension; LVDd, left ventricular end diastolic dimension; LVPW, left ventricular posterior wall.

However, the patient’s condition was not improved despite optimized medication. On 26 January 2021, the patient was re-admitted with recurrent chest distress and oedema, with new symptoms of facial plethora, centripetal obesity, and hyperglycaemia (Figure S1). Abdominal CT scan showed a right adrenal adenoma (Figure 2). Cardiac magnetic resonance imaging revealed enlarged LVDd (62 mm), and reduced EF, with delayed myocardial enhancement and evidence of myocardial fibrosis and fatty deposits (Figure 3). Laboratory findings showed hypokalaemia: potassium 3.0 mmol/L, elevated serum cortisol level, low plasma ACTH level, and positive 1-mg overnight dexamethasone suppression test. Based on the above findings, the patient was diagnosed with Cushing’s syndrome and started treatment with the glucocorticoid receptor inhibitor mifepristone on 5 February 2021.

Details are in the caption following the image

Abdominal CT scan showed adrenal adenoma at the right.

Details are in the caption following the image

Cardiac magnetic resonance imaging revealed enlarged LVDd, reduced EF, with delayed myocardial enhancement, evidence of myocardial fibrosis and fatty deposits.

With mifepristone added to the previous medical therapy (aspirin, statin, sacubitril/valsartan, metoprolol and diuretic of furosemide and spirolactone, and mifepristone), the patient’s condition and cardiac function improved, and echocardiography (21 December 2021) showed increased EF (52.5%). The patient underwent partial adrenalectomy on 22 December 2021. Postoperative pathology confirmed adrenal cortical adenoma. At last follow-up on 29 May 2023, the patient showed marked improvement in face and body shape, with no complaints of chest distress or oedema (Figure S2).

Discussion

In this case, the patient was first evaluated for STEMI due to her symptoms of chest pain, and the elevated ST-segment on ECG, along with the moderately elevated troponin I and other cardiac enzyme levels. However, coronary atherosclerotic heart disease was ruled out by the normal cardiac catheterization. We presume that a possible reason for acute myocardial infarction (AMI) might be vasospastic angina due to abnormal hormone levels with Cushing’s syndrome, leading to increased excessive myocardial metabolic demand and relative myocardial hypoxia, which eventually induced myocardial infarction. Although coronary atherosclerotic heart disease is the main cause of AMI, many non-atherosclerotic processes can lead to an imbalance between decreased coronary blood flow and increased myocardial metabolic demand. To date, non-atherosclerotic myocardial infarction has rarely been reported in Cushing’s syndrome patients. Vieira JT et al. reported that a patient with Cushing’s disease was considered to have spontaneous coronary artery dissection, which is a rare reason for AMI.2

Cushing’s syndrome is associated with an increased risk of cardiac failure,3 with both structural alterations and functional impairment. In our case, the patient’s CMR imaging showed typical features of cardiac geometry, function, and fibrosis, in accordance with previous reports.4 The underlying mechanisms may be the enhanced responsiveness to angiotensin II and activation of the mineralocorticoid receptor in direct response to cortisol excess.5

Our patient responded well to the therapy of conventional anti-HF medication of sacubitril/valsartan, metoprolol, and diuretic, once mifepristone was added. This favourable response to the pharmacological regimen supports the benefits of the agents for the normalization of excess cortisol. This case indicates that early diagnosis and effective treatment of Cushing’s syndrome may be crucial in preventing irreversible cardiac dysfunction secondary to cardiovascular events and heart failure.

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (81900409 and 82172182) and the PLA Youth Training Project for Medical Science (19QNP037).

Conflict of interest

The authors declares that there is no conflict of interest.

From https://onlinelibrary.wiley.com/doi/10.1002/ehf2.14548

Filed under: adrenal, Cushing's, symptoms | Tagged: , , , , , | Leave a comment »

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

Posted on August 8, 2020 by MaryO

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

Primary Source

Annals of Internal Medicine

Source Reference: Yao TC, et al “Association between oral corticosteroid bursts and severe adverse events: a nationwide population-based cohort study” Ann Intern Med 2020; DOI: 10.7326/M20-0432.

Secondary Source

Annals of Internal Medicine

Source Reference: Wallace BI, Waljee AK “Burst case scenario: why shorter may not be any better when it comes to corticosteroids” Ann Intern Med 2020; DOI: 10.7326/M20-4234.

Additional Source

MedPage Today

Source Reference: Lou N “Sobering Data on Risks of Short-Term Oral Corticosteroids” 2020.

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

Filed under: Rare Diseases | Tagged: , , , , | Leave a comment »

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

Posted on May 12, 2015 by MaryO

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

Filed under: adrenal, Cushing's, podcast, Rare Diseases, Treatments | Tagged: , , , , , , , , , , , , , , , , , , , | 2 Comments »