Joint Pain Supplement Tied to Patient's Weight Gain, Stretch Marks

— Case of iatrogenic Cushing's syndrome highlights importance of asking about supplement use

A supplement marketed for joint pain and arthritis was the likely culprit in one man's iatrogenic Cushing's syndrome, researchers reported.

A man in his 40s presented with features of Cushing's syndrome, including rapid weight gain and stretch marks on his abdomen, Hima Darapu, MD, of Wake Forest Baptist Medical Center in Winston-Salem, and Sagarika Gokul, MD, of Prisma Health in Greenville, both in South Carolina, wrote in BMJ Case Reportsopens in a new tab or window.

Cushing's is usually the result of prolonged glucocorticoid exposure, either through natural processes or taking medications containing them, the researchers explained.

The patient denied taking any glucocorticoids, but did report taking a supplement called Artri King Reforzado Con Ortiga Y Omega 3 for joint pain. He viewed it as a natural remedy that a colleague had recommended to him, the authors noted, but the FDA had previously recalled itopens in a new tab or window for undeclared dexamethasone.

The patient took it for 9 months before his symptoms started.

"This case highlights the serious and often overlooked dangers posed by unregulated over-the-counter supplements containing undeclared pharmacologically active substances," Darapu and Gokul wrote.

The presence of dexamethasone in this product was "the likely etiology" of idiopathic Cushing's syndrome in this case, they noted, adding that multiple adverse eventsopens in a new tab or window, including hepatotoxicity and fatalities, have been reported with Artri King products.

Maria Fleseriu, MD, director of the Pituitary Center at Oregon Health & Science University in Portland, who was not involved in the report, said more awareness is needed about these kinds of supplements.

"We clearly see a few of these cases per year in clinic, and more frequently than before, especially with arthritis supplements bought on the internet," Fleseriu told MedPage Today. "Some supplements have been found to contain undeclared glucocorticoids, which is more complex as patients do not even know, but are producing classic Cushingoid features while suppressing ACTH [adrenocorticotropic hormone] and endogenous cortisol production."

"Many case reports, including this one, have also documented Cushing syndrome from contaminated or higher doses than declared of herbal supplements, highlighting the importance of a careful supplement history," she added.

Iatrogenic Cushing's syndrome is most commonly due to prescribed glucocorticoids, but "hidden glucocorticoids in over-the-counter supplements are an emerging cause," Darapu and Gokul wrote. "Adulterated 'natural' supplements can lead to severe endocrine disruptions, and their identification requires high clinical suspicion and meticulous history taking."

In this case, the patient had a 6-month history of progressive fatigue, intermittent nausea, bilateral foot discomfort, and unintentional weight gain in excess of 99 lbs. He had type 2 diabetes, hypertension, arthritis, and a history of obesity with significant weight loss from lifestyle changes.

Examination showed he had "Cushingoid" features, with marked truncal obesity, facial rounding, wide, pinkish-violaceous stretch marks over the lower abdomen, as well as mild proximal muscle weakness in both upper and lower limbs.

Pituitary MRI was negative for a lesion, and testing confirmed low morning cortisol and ACTH levels. Since his symptoms suggested Cushing's, but he denied glucocorticoid use, an endocrine workup was done to assess both exogenous glucocorticoid exposure and endogenous cortisol excess.

It was on further questioning that the patient reported using the joint supplement. Cushingoid changes had started while he was taking it, and the rest of the symptoms started a few weeks after he discontinued, the authors wrote.

The patient was started on physiologic hydrocortisone replacement for secondary adrenal insufficiency. Treatment was gradually tapered over time while monitoring for recovery of hypothalamic-pituitary-adrenal axis function, and discontinued after adrenal function fully recovered, about 4 months after the start of treatment.

His symptoms gradually improved, although he was unable to lose weight because of his arthritis, the researchers reported. He eventually underwent bariatric surgery, and his blood glucose normalized with the resulting weight loss. The patient also received education on the signs of adrenal insufficiency, and counseling on the dangers of unregulated supplements.

Despite the FDA safety alerts and recalls, these supplements remain available both online and through retail markets, the authors said, "highlighting persistent regulatory gaps and the need for stronger oversight along with improved public and clinician awareness to prevent inadvertent glucocorticoid exposure from adulterated products."

Although this case was not reported to the FDA at the time of initial presentation, it was reported later.