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Three Cases of Ectopic, Cyclic Cushing Syndrome: A New Square Wave Variant
Journal article   Open access   Peer reviewed

Three Cases of Ectopic, Cyclic Cushing Syndrome: A New Square Wave Variant

Mercedes Martinez-Gil, Tshibambe N Tshimbombu, Yvette Li Yi Ang, Monica C Rodriguez and Kevin C J Yuen
JCEM case reports, Vol.3(12), p.luaf176
12/01/2025
PMID: 41163704

Abstract

ectopic hypercortisolemia eucortisolemia cyclic Cushing syndrome
Cyclic Cushing syndrome (CCS) is characterized by unpredictable, intermittent phases of excess cortisol, alternating with periods of normal or subnormal adrenocorticotropic hormone (ACTH) and cortisol levels. The mechanism is unclear. Due to its rarity and diverse clinical presentation, unpredictable phases, and various etiologies, CCS poses significant diagnostic and management challenges for endocrinologists. The authors describe 3 cases in which each patient's initial presentation was a life-threatening hypercortisolemic phase that lasted from 4 days to 3 months, followed by spontaneous resolution to prolonged eucortisolemic phases lasting from 10 to 26 months. Further testing indicated an ectopic ACTH-secreting source; however, the locations of the offending tumors were indeterminate. The authors propose the term CCS variant to characterize the unique, prolonged intercyclic phases of hypercortisolemia and eucortisolemia with this subtype that are distinct from conventional CCS characterized by shorter phases of transient hypercortisolemia shifting to periods of eucortisolemia or hypocortisolemia. This uncharacteristic pattern of cyclicity poses diagnostic and therapeutic challenges, thus underscoring the importance of careful diagnostic workup and treatment of these patients.
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https://doi.org/10.1210/jcemcr/luaf176View
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