Interaction between medicines leads to man’s Cushing’s syndrome

Man, 45, was being treated with combination of antiviral therapies, corticosteroid

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A person weighs a choice between two medicines.

A man developed Cushing’s syndrome as a result of an interaction between two medications he was taking — an antiviral therapy to treat chronic infections and an inhaled steroid to manage asthma — according to a recent report.

“This clinical case illustrates the importance of a meticulous review of all ongoing therapy before starting a new drug,” the researchers wrote in the study, “Iatrogenic Cushing’s Syndrome: The Result of Cobicistat and Glucocorticoid Interaction in an HIV Patient After Bariatric Surgery,” which was published in Cureus.

Cushing’s syndrome is marked by elevated levels of cortisol, a stress hormone. Cushing’s disease is a specific form of the syndrome caused by a tumor in the pituitary gland.

Some medications can interfere with cortisol levels and give rise to Cushing’s syndrome, a condition known as iatrogenic, or medication-induced, Cushing’s.

Scientists in Portugal described the case of a 45-year-old man who was positive for infection with hepatitis C and human immunodeficiency virus. Since 2019, he’d been taking a combination of antiviral therapies, including raltegravir, darunavir, and cobicistat.

The man underwent a sleeve gastrectomy — surgery to remove part of the stomach — to promote weight loss in 2021. Four months later, at which point he’d lost 26 kg (more than 57 pounds), he was diagnosed with asthma, for which he was prescribed inhaled corticosteroids — initially budesonide, which was then switched to fluticasone propionate. Corticosteroids are a class of medicines that mimic cortisol’s activity in the body. Since cortisol reduces inflammation, these medicines are used manage conditions like asthma.

A year after his surgery, the man began having muscle weakness that made walking difficult. At this point, his weight loss was “suboptimal,” according to researchers. Despite sticking to his nutrition plan, he’d lost only about 30 kg (around 66 pounds), less than 40% of what he’d intended to lose.

A physical examination showed several signs of Cushing’s syndrome, including an abnormal accumulation of fat between the shoulder blades (buffalo hump), a rounded face, and purplish stripes across his abdomen.

Lab tests revealed high blood sugar and low potassium levels, which are common in Cushing’s, and further tests confirmed the diagnosis.

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“After a complete review of his clinical history, it was confirmed that this unsatisfactory response to [weight loss] surgery coincided with the introduction of inhaled corticosteroids due to asthma and with the development of suggestive signs and symptoms of [Cushing’s],” the researchers wrote.

The researchers determined that the antiviral therapy cobicistat blocks the activity of a liver enzyme called CYP3A4, which normally helps break down corticosteroids.

In this patient, inhibiting CYP3A4 meant he was getting higher levels of corticosteroids in his system. Since corticosteroids mimic the natural activity of cortisol, this resulted in the onset of Cushing’s.

The man’s medications were changed from darunavir and cobicistat to dolutegravir and doravirine, antiviral therapies that don’t interact with CYP3A4. His inhaled corticosteroid was switched to beclomethasone, which is not as long-lasting in the body, and he was given an oral corticosteroid (prednisolone) to help normalize cortisol levels.

Two weeks after changing treatments, the man’s muscle weakness had markedly eased and he’d lost 6 kg (more than 13 pounds).

“Management was sufficient for the attenuation of clinical manifestations and weight loss in just about two weeks, in a safe way,” the researchers wrote, noting the study highlights the importance of considering potential interactions between medications when prescribing a new therapy, and especially when using corticosteroids with patients on cobicistat or other therapies that block CYP3A4.

“Anticipating potential complications and therapeutic interactions is essential for the best decisions and adjustments to be made to avoid serious harm to the patient,” they wrote.