A rare case study published in JCEM Case Reports details the first known instance of a decades-dormant hormonal disorder, Cyclic Cushing Syndrome (CS), relapsing after a patient contracted COVID-19 and received standard glucocorticoid treatment. The relapse occurred after a remarkable 19-year period of remission, leading researchers to suggest that the stress of the infection and the administered steroids may have triggered a rare “positive feedback” loop, reigniting the life-threatening condition. The case highlights the critical need for long-term patient follow-up and caution when administering steroids to individuals with a history of the disorder.
The patient, a 49-year-old man, had initially been diagnosed with adrenocorticotropic hormone (ACTH)-dependent CS at age 30 but achieved spontaneous remission after initial treatment with steroidogenesis inhibitors (trilostane and mitotane). A subtype of Cushing’s syndrome, patients with CS have phases of cortisol excess—hypercortisolemia–alternating with phases of normal and low cortisol. Each of these phases can vary from days to even months or years. For nearly two decades, this patient’s condition remained stable, with no cushingoid symptoms or abnormal hormone levels noted during annual checkups.
The clinical picture changed drastically when he was infected with COVID-19. Following the infection, and after receiving a month-long regimen of high-dose glucocorticoid treatment (including methylprednisolone and prednisolone) to manage the viral symptoms, the patient developed classic signs of Cushing’s syndrome relapse. These symptoms included general fatigue, 11 kg of weight gain, “moon face,” and dangerously high blood pressure, leading to his readmission to the hospital.
Researchers at The University of Osaka noted that the mechanism of relapse appeared to be highly unusual. Cyclic CS, characterized by fluctuating hypercortisolemia, typically operates under a negative feedback system. However, in this case, the introduction of exogenous glucocorticoids (the COVID-19 treatment) seemed to have paradoxically driven a positive feedback mechanism, stimulating the body to produce even more ACTH and cortisol. The authors hypothesize that this rare mechanism made the patient susceptible to a relapse when faced with the combined stress of the infection and the administered steroid therapy.
The authors urge clinicians to “pay attention to the development of cushingoid symptoms after infection stress and glucocorticoid treatment,” emphasizing that long-term, careful follow-up is essential for patients with uncured cyclic CS, even after years of apparent remission.
The relapse was confirmed by severely elevated plasma ACTH and hypercortisolism. Initially, diagnostic tests suggested Cushing’s disease (a pituitary cause), but subsequent imaging failed to detect a pituitary tumor. Further investigative scans ultimately revealed an 8-mm tumor in the anterior mediastinum. This led to a diagnosis of an ACTH-secreting thymic typical carcinoid tumor, a form of ectopic CS, which was confirmed when partial thymectomy resulted in the patient’s third remission. This fluctuation in hormone levels also complicated the diagnostic process, underscoring the challenge of accurately diagnosing CS during its natural “trough phase.”
The report, “Relapse of Cyclic Cushing Syndrome With a 19-Year Remission: Potential Involvement of COVID-19 in the Relapse,” concludes that the stress from a severe infection, such as COVID-19, coupled with the administration of glucocorticoids, can potentially act as a trigger for relapses in uncured cyclic CS patients who harbor this rare positive feedback mechanism. The case serves as a vital learning point for physicians globally. The authors urge clinicians to “pay attention to the development of cushingoid symptoms after infection stress and glucocorticoid treatment,” emphasizing that long-term, careful follow-up is essential for patients with uncured cyclic CS, even after years of apparent remission.
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