PMC5768610_01
Salivary cortisol levels before and after initiation of metyrapone treatment. (A) Patient No. 1. (B) Patient No. 2. (C) Patient No. 3. (D) Patient No. 4. (E) Patient No. 5. (F) Patient No. 6. (G) Salivary cortisol levels at 6:00 a.m. (before administration) and 8:00 a.m. (2 h after administration).
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F1
In Patient No. 1, both the UFC and morning serum cortisol levels decreased after initiation of metyrapone treatment in a dose-dependent manner (Figure 1A). However, multiple measurements of salivary cortisol levels revealed relatively lower cortisol levels in the morning and higher levels in the daytime and night, indicating that the diurnal cortisol rhythm was still impaired in this patient (Figure 1A). Similar results were observed in Patients No. 3 and 4 (Figures 1C,D). In Patient No. 2 (Figure 1B), the serum cortisol and UFC levels did not change with 750 mg of metyrapone, while the MV and AUC of salivary cortisol levels decreased. Salivary cortisol levels revealed that, even with the dose of metyrapone 2,000 mg, the CS remained uncontrolled, and obvious impairment of the diurnal cortisol rhythm remained (Figure 1E). However, the diurnal rhythm was not fully reconstituted (Figure 1F).
Changes in the diurnal salivary cortisol pattern after the optimization of timing of metyrapone administration in Patient No. 4.
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F2
During the second admission, although the dose of metyrapone was increased to 2,250 mg, the UFC level rather increased (Figure 2). As a result, the diurnal salivary cortisol pattern was obviously improved, despite the slight increase in the total daily dose (Figure 2).