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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Pituitary Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1511155

Metyrapone single administration, as a possible predictive tool of its dosage and timing in Cushing's syndrome

Provisionally accepted
Yasutaka Tsujimoto Yasutaka Tsujimoto 1Naoki Yamamoto Naoki Yamamoto 1Hironori Bando Hironori Bando 2Masaaki Yamamoto Masaaki Yamamoto 1Yuka Ohmachi Yuka Ohmachi 1Yuma Motomura Yuma Motomura 1Yuka Oi-Yo Yuka Oi-Yo 1Yuriko Sasaki Yuriko Sasaki 1Masaki Suzuki Masaki Suzuki 1Shin Urai Shin Urai 2Michiko Takahashi Michiko Takahashi 3Genzo Iguchi Genzo Iguchi 4Wataru Ogawa Wataru Ogawa 1Hidenori Fukuoka Hidenori Fukuoka 2*
  • 1 Division of Diabetes and Endocrinology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyōgo, Japan
  • 2 Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Hospital, Kobe, Japan
  • 3 Department of Nutrition, Kobe University Hospital, Kobe, Japan
  • 4 Department of Clinical Nutrition and Dietetics, Konan Women’s University, Kobe, Japan

The final, formatted version of the article will be published soon.

    Metyrapone is commonly used in the initial management of Cushing's syndrome to reduce hypercortisolemia, but its optimal dosage and timing can vary significantly between patients. Currently, there are limited guidelines on adjustment methods for its administration to individual needs. This study aimed to evaluate responsiveness of each patient to metyrapone and identify the patient characteristics associated with the indices of cortisol responsiveness following a low-dose metyrapone. This single-center retrospective observational study included 15 treatment-naïve patients, 7 of whom had Cushing's disease and 8 had adrenal Cushing's syndrome. Serum cortisol levels were measured hourly from the time of administration of 250 mg of metyrapone up to four hours afterward. Parameters analyzed included the nadir of serum cortisol levels (Fnadir), the difference between basal and nadir serum cortisol levels (ΔF), the time to nadir, and the characteristics of the patients. As a result, cortisol suppression curves showed significant variability among patients, particularly in the time to nadir. While the median time to nadir was 2 hours, 20% of patients required 4 hours or more, and these responses were not associated with patient characteristics. Fnadir was positively correlated with early-morning serum cortisol levels, serum cortisol levels after low-dose dexamethasone suppression test (LDDST), and urinary free cortisol (UFC) levels, whereas ΔF was positively correlated with late-night serum cortisol levels, serum cortisol levels after LDDST, and UFC levels. In conclusion, the duration of response to metyrapone appeared unpredictable in patients with Cushing's syndrome and did not correlate with patient characteristics at baseline. Tracking the effect of metyrapone following a single low-dose administration may explain this variability and provide insights for optimizing individual dosing regimens. Further studies are required to validate these findings and guide more personalized treatment adjustments.

    Keywords: Cushing's syndrome, Cushing's disease, Metyrapone, hypercortisolemia, drug responsiveness, monitoring marker

    Received: 14 Oct 2024; Accepted: 03 Dec 2024.

    Copyright: © 2024 Tsujimoto, Yamamoto, Bando, Yamamoto, Ohmachi, Motomura, Oi-Yo, Sasaki, Suzuki, Urai, Takahashi, Iguchi, Ogawa and Fukuoka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hidenori Fukuoka, Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Hospital, Kobe, Japan

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