Relapse of Cyclic Cushing Syndrome With a 19-Year Remission: Potential Involvement of COVID-19 in the Relapse.

Cyclic Cushing syndrome (cyclic CS) is characterized by phases of hypercortisolemia and normocortisolemia or hypocortisolemia. Here, we present the first case of cyclic CS with a relapse following COVID-19 infection and a long-term normocortisolemic phase of 19 years. The patient developed CS at the age of 30. The first remission of CS was achieved by the use of steroidogenesis inhibitors and was eventually maintained without the use for 19 years. At the age of 49, the patient suffered from COVID-19 infection and was treated with glucocorticoids, after which the patient developed CS relapse. Intriguingly, the second remission was induced by steroidogenesis inhibitors. Therefore, the cyclic CS in the present case could be dependent on a glucocorticoid-driven positive feedback mechanism. Although the diagnostic tests for CS suggested Cushing disease, no pituitary tumors were detected. However, radionuclide scanning revealed a thymic tumor. Partial thymectomy resulted in the third remission. The patient was eventually diagnosed with ACTH-secreting thymic typical carcinoid tumors. The present case suggests that careful follow-up is essential for patients with uncured cyclic CS even if long-term remission is achieved. Additionally, a relapse of cyclic CS with a glucocorticoid-driven positive feedback mechanism could be induced by infection and treatment with glucocorticoids.