Effects of Metyrapone on ACTH Secretion in Patients with ACTH-Dependent Cushing’s Syndrome

Presentation Number: SAT 414
Date of Presentation: April 1st, 2017

Keisuke Kakizawa*, Yutaka Okawa, Miho Yamashita and Yutaka Oki
Hamamatsu University School of Medicine, Hamamatsu, Japan



In patients with Cushing’s syndrome, we have to use metyrapone frequently to control severe hypercortisolemia before surgery. Theoretically, plasma ACTH increases after metyrapone treatment in patients with Cushing’s disease (CD). However, we have experienced that plasma ACTH decreased after its treatment in some patients with CD. In this study, we investigated the background of those patients retrospectively.


Fifteen patients with Cushing’s disease (CD) were divided into two groups. Eight patients showed that plasma ACTH increased one week after metyraponse initiation (group A). On the other hand, seven patients showed that plasma ACTH decreased after metyrapone (group B). The clinical backgrounds were compared between two groups.


The doses of metyrapone between in group A and B were not different (3000 ± 755 vs, 2000 ± 800 mg/day), respectively. Urinary free cortisol excretions between in both groups were not different (490 ± 618 vs. 382 ± 1368 μg/day). Plasma ACTH levels were greater in group B than in group A (138 ± 49 vs. 186 ± 149 pg/mL, P<0.05). Plasma ACTH responses to CRH were greater in group A than in group B (401± 304 vs. 39 ± 2.9% of basal levels, P< 0.03). The sizes of pituitary adenomas were significantly larger in group B than group A (25 ± 9.4 vs. 6 ± 4.0 mm in diameter, P<0.005).

[Discussion and Conclusion]

ACTH secretion from pituitary is negatively regulated by glucocorticoid. Therefore, metyrapone, a 11 beta hydroxylase inhibitor, theoretically decreases plasma cortisol and subsequently plasma ACTH level increases. From our results, CD with macroadenoma and low ACTH response to CRH may show the ACTH suppression by metyrapone. These suggest that glucocorticoid unexpectedly stimulate ACTH secretion in some patients with CD.


Nothing to Disclose: KK, YO, MY, YO