IVIG Therapy May Be Effective, Safe for COVID-19 in Cushing’s Patients

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by Vanda Pinto, PhD |

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A 70-year-old woman with ectopic Cushing’s syndrome was successfully treated for COVID-19 with intravenous immunoglobulins (IVIg) — a therapy prepared from the blood of thousands of healthy donors that contains a mixture of antibodies — according to a case report.

Given the lack of guidelines for the management of COVID-19 in patients with active Cushing’s syndrome, this case suggests a possible effective and safe treatment option for similar cases.

The report, “Successful Immunomodulatory Treatment of COVID-19 in a Patient With Severe ACTH-Dependent Cushing’s Syndrome: A Case Report and Review of Literature,” was published in the journal Frontiers in Endocrinology.

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Cushing’s syndrome is a disorder characterized by hypercortisolism — the excessive production of the steroid hormone cortisol. One of the main causes of this are tumors in the brain’s pituitary gland, a condition known as Cushing’s disease. These tumors produce too much adrenocorticotropic hormone (ACTH), which in turn stimulates the production of cortisol by the adrenal glands, located on top of the kidneys.

In ectopic Cushing’s syndrome, ACTH-producing tumors arise in organs and tissues outside the pituitary gland, such as in the pancreas, lungs, and thyroid gland. Diagnosis can be difficult due to the relatively small size of these masses.

Since hypercortisolism can suppress the immune system, people with Cushing’s syndrome are at a higher risk of contracting opportunistic bacterial, fungal, and viral infections.

Until now, only two small case series have followed patients with Cushing’s disease in different disease stages during the COVID-19 pandemic, according to researchers. As a result, the clinical course and outcomes of patients with Cushing’s syndrome and COVID-19, as well as specific therapeutic guidelines, have yet to be determined.

Case of ectopic Cushing’s with severe COVID-19

In the report, researchers in Serbia have documented the case of a woman with ectopic Cushing’s who developed a severe form of COVID-19 and was successfully treated with IVIg therapy — a treatment used in several autoimmune and infectious diseases because of its immunomodulatory properties.

“To our knowledge, this is the first case of IVIg treatment in a COVID-19 patient with [Cushing’s syndrome],” the researchers wrote.

The patient was admitted to hospital with pneumonia caused by an infection with SARS-CoV-2, the virus that causes COVID-19. She had been previously vaccinated with two doses of the Sinopharm/BBIBP COVID-19 vaccine.

Six days earlier, she had left the endocrinology department of another hospital where she was admitted for diabetes mellitus. This time, doctors noticed she had several typical symptoms of Cushing’s, including hypertension (high blood pressure), rounded face (“moon face”), accumulation of fat around the waist (central obesity), and several bruises.

Her morning blood ACTH levels were high (92.6 picograms per milliliter (pg/mL); normal range is 10–60 pg/mL), and so were her morning blood cortisol levels (1,239 nanomoles per liter (nmol/L); normal range is 131–642 nmol/L). Her cortisol levels did not decline after a dexamethasone suppression test, suggesting she had an ACTH-dependent form of Cushing’s syndrome.

No pituitary tumor was detected on MRI brain scans. Additionally, no tumors were found after she underwent a chest CT scan.

Although she was referred to another hospital for specialized care, the patient tested positive for COVID-19. The woman was ultimately hospitalized due to the severity of her symptoms, which included pneumonia, fever, low blood oxygen levels, shortness of breath, and rapid breathing.

Because of her hypercortisolism, doctors could not treat her COVID-19 symptoms with glucocorticoids, a class of steroid hormones that possess strong anti-inflammatory and immunosuppressive properties.

Instead, they decided to treat her with IVIg therapy for five days, along with antibiotics for pneumonia, and oxygen therapy. No side effects from any of the treatments were observed and her condition quickly improved.

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The patient was discharged after a few days and received a referral to a tertiary institution to start treatment and further testing for Cushing’s.

“It is our opinion that immune-modulating properties of IVIg might present an attractive treatment option, especially in those [Cushing’s syndrome] patients that show rapid clinical progression and positive laboratory parameters of inflammation,” the researchers wrote.

“While we await for new therapeutic modalities for COVID-19 and while some of the modalities remain not widely available, IVIg is [a] more accessible, safe method, which could be rescuing in carefully selected patients,” they wrote.

The researchers also noted the fact the patient had been previously vaccinated for COVID-19 and that might have contributed to her positive outcome.