Tumor Shrinkage by Metyrapone in Cushing Disease Exhibiting Glucocorticoid-Induced Positive Feedback
| Autor: | Takamitsu Imanishi, Hiroki Shichi, Yutaka Takahashi, Itsuko Sato, Yasutaka Tsujimoto, Shozo Yamada, Kazuo Chihara, Hidenori Fukuoka, Masaaki Yamamoto, Atsushi Ishida, Naoko Inoshita, Tomoaki Nakamura |
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| Rok vydání: | 2021 |
| Předmět: |
3D culture
0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism tumor shrinkage 030209 endocrinology & metabolism Context (language use) Adrenocorticotropic hormone 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Clinical Research Articles Dexamethasone Metyrapone business.industry Cushing disease metyrapone Pituitary tumors positive feedback medicine.disease Cushing Disease 030104 developmental biology Endocrinology Dexamethasone suppression test business AcademicSubjects/MED00250 Glucocorticoid medicine.drug |
| Zdroj: | Journal of the Endocrine Society |
| ISSN: | 2472-1972 |
| DOI: | 10.1210/jendso/bvab055 |
| Popis: | Context Paradoxical increases in serum cortisol in the dexamethasone suppression test (DST) have been rarely observed in Cushing disease (CD). Its pathophysiology and prevalence remain unclear. Case Description A 62-year-old woman with suspected CD showed paradoxical increases in cortisol after both 1-mg and 8-mg DST (1.95-fold and 2.52-fold, respectively). The initiation of metyrapone paradoxically decreased plasma adrenocorticotropic hormone (ACTH) levels and suppressed cortisol levels. Moreover, the pituitary tumor considerably shrank during metyrapone treatment. Ex Vivo Experiments The resected tumor tissue was enzymatically digested, dispersed, and embedded into Matrigel as 3D cultured cells. ACTH levels in the media were measured. In this tumor culture, ACTH levels increased 1.3-fold after dexamethasone treatment (P < 0.01) while control tumor cultures exhibited no increase in ACTH levels, but rather a 20% to 40% suppression (P < 0.05). Clinical Study A cross-sectional, retrospective, multicenter study that included 92 patients with CD who underwent both low-dose and high-dose DST from 2014 to 2020 was performed. Eight cases (8.7%) showed an increase in serum cortisol after both low-dose and high-dose DST. Conclusion This is the first report of a patient with glucocorticoid (GC)-driven positive feedback CD who showed both ACTH suppression and tumor shrinkage by metyrapone. Our cohort study revealed that 8.7% of patients with CD patients possibly possess GC-driven positive-feedback systems, thereby suggesting the presence of a new subtype of CD that is different from the majority of CD cases. The mechanisms exhibiting GC positive feedback in CD and the therapeutic approach for these patients remain to be investigated. |
| Databáze: | OpenAIRE |
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