ACTH-Dependent Cyclic Cushing Syndrome Triggered by Glucocorticoid Excess Through a Positive-Feedback Mechanism

• Published in: The journal of clinical endocrinology and metabolism Vol. 104; no. 5; pp. 1788 - 1791
• Main Authors: Seki, Yasufumi, Morimoto, Satoshi, Saito, Fumiko, Takano, Noriyoshi, Kimura, Shihori, Yamashita, Kaoru, Yoshida, Naohiro, Bokuda, Kanako, Sasaki, Nobukazu, Yatabe, Midori, Watanabe, Daisuke, Yatabe, Junichi, Ando, Takashi, Amano, Kosaku, Kawamata, Takakazu, Ichihara, Atsuhiro
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.05.2019; Copyright Oxford University Press; Oxford University Press
• Subjects: ACTH; Adrenal glands; Adrenocorticotropic hormone; Adrenocorticotropic Hormone - metabolism; Aged; Cushing syndrome; Cushing Syndrome - chemically induced; Cushing Syndrome - metabolism; Cushing Syndrome - pathology; Dexamethasone; Dexamethasone - adverse effects; Feedback; Female; Glucocorticoids; Glucocorticoids - adverse effects; Hormones; Humans; Hydrocortisone; Nervous system diseases; Periodicity; Pituitary; Prognosis; Remission; Japan
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-02268

Abstract Context Cyclic Cushing syndrome is a rare variant of Cushing syndrome that demonstrates periodic cortisol excess. It has been thought that inhibition of a glucocorticoid positive-feedback loop is associated with remission of hypercortisolism in ACTH-dependent cyclic Cushing syndrome. However, the underlying mechanism that triggers the development of the hypercortisolism is still unknown. We observed a case of ACTH-dependent cyclic Cushing syndrome that was developed by exogenous glucocorticoids, possibly through a glucocorticoid positive-feedback loop. Case Description A 75-year-old woman had experienced cyclic ACTH and cortisol elevations six times in the previous 4 years. Her diagnosis was cyclic Cushing syndrome. During the hypercortisolemic phase, neither low-dose nor high-dose dexamethasone suppressed her plasma ACTH and cortisol levels. Daily metyrapone therapy decreased her plasma cortisol and ACTH levels during every hypercortisolemic phase. After the sixth remission of a hypercortisolemic phase, she took 25 mg of hydrocortisone for 4 weeks and developed ACTH-dependent hypercortisolemia. Treatment with 1 mg of dexamethasone gradually increased both plasma ACTH and cortisol levels over 2 weeks, resulting in the eighth hypercortisolemic phase. Treatment using a combination of dexamethasone and metyrapone did not increase plasma ACTH or cortisol level and successfully prevented development of ACTH-dependent hypercortisolism. Conclusion We present an interesting case of cyclic Cushing syndrome in which ACTH-dependent hypercortisolemic phases relapsed during exogenous glucocorticoid treatment. A glucocorticoid positive-feedback loop and endogenous glucocorticoid synthesis may play key roles in the periodicity of hypercortisolism in cyclic Cushing syndrome. We present a case of exogenous glucocorticoid-triggered ACTH-dependent cyclic Cushing syndrome and propose possible mechanisms for the periodicity of hypercortisolism.