Yoshida Kenichi, Fukuoka Hidenori, Odake Yukiko, Nakajima Shinsuke, Tachibana Mariko, Ito Jun, Hosokawa Yusei, Yamada Tomoko, Miura Hiroshi, Suematsu Natsu, Matsumoto Ryusaku, Bando Hironori, Suda Kentaro, Nishizawa Hitoshi, Iguchi Genzo, Ogawa Wataru, Takahashi Yutaka
Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.
Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan.
Front Endocrinol (Lausanne). 2018 Jan 11;8:375. doi: 10.3389/fendo.2017.00375. eCollection 2017.
Measuring salivary cortisol is both convenient and non-invasive for patients; however, its usefulness as a marker for monitoring medical therapy has not yet been established. The aim of this study was to assess the utility of multiple salivary cortisol measurements in patients with Cushing's syndrome (CS) during medical therapy. Six patients with CS (three with cortisol-secreting adrenocortical adenoma and three with ACTH-secreting pituitary adenoma) were recruited. Samples for morning serum cortisol, urinary free cortisol (UFC), and multiple salivary cortisol levels were collected before and during metyrapone treatment. The area under the curve (AUC) and mean value (MV) of daily salivary cortisol levels were calculated. In five out of six patients, UFC were normalized; however, multiple salivary cortisol measurements revealed an impaired diurnal cortisol rhythm in these patients. To verify the usefulness of multiple salivary cortisol measurements, we performed a prospective case study of a patient in whom the excess secretion of cortisol was not controlled (UFC 211 μg/day) with 2,250 mg/day in four divided doses of metyrapone. Multiple measurements of salivary cortisol revealed that cortisol levels elevated before the next administration. Accordingly, we shortened the interval by increasing the number of administration from four to five times per day, with a slight increment of daily dose of 2,500 mg. These optimizations resulted in a drastic improvement of diurnal pattern as well as UFC level (101 μg/day). Changes in both the MV and AUC of salivary cortisol levels were more correlated with those in UFC levels (Correlation coefficient 0.75, = 0.007, and 0.70, = 0.017) than those in the morning serum cortisol levels (0.42, = 0.200), indicating that multiple salivary cortisol measurements reflect more precisely the excess secretion of cortisol. Our preliminary data suggest that multiple salivary cortisol measurements can be a useful tool to visualize the diurnal cortisol rhythm and to determine the dose and timing of metyrapone during the treatment in patients with CS.
对患者而言，测量唾液皮质醇既方便又无创；然而，其作为监测药物治疗标志物的效用尚未得到证实。本研究的目的是评估在库欣综合征（CS）患者药物治疗期间多次测量唾液皮质醇的效用。招募了6例CS患者（3例为分泌皮质醇的肾上腺皮质腺瘤患者，3例为分泌促肾上腺皮质激素的垂体腺瘤患者）。在甲吡酮治疗前和治疗期间收集早晨血清皮质醇、尿游离皮质醇（UFC）以及多次唾液皮质醇水平的样本。计算每日唾液皮质醇水平的曲线下面积（AUC）和平均值（MV）。6例患者中有5例的UFC恢复正常；然而，多次唾液皮质醇测量显示这些患者的皮质醇昼夜节律受损。为验证多次唾液皮质醇测量的效用，我们对1例患者进行了前瞻性病例研究，该患者使用甲吡酮每日2250mg分4次给药时皮质醇分泌过多未得到控制（UFC为211μg/天）。多次唾液皮质醇测量显示在下一次给药前皮质醇水平升高。因此，我们通过将给药次数从每天4次增加到5次来缩短间隔时间，同时将每日剂量略微增加至2500mg。这些优化措施使昼夜模式以及UFC水平（101μg/天）得到了显著改善。唾液皮质醇水平的MV和AUC变化与UFC水平变化的相关性（相关系数分别为0.75，P = 0.007和0.70，P = 0.017）高于与早晨血清皮质醇水平变化的相关性（0.42，P = 0.200），这表明多次唾液皮质醇测量能更准确地反映皮质醇的分泌过多情况。我们的初步数据表明，多次唾液皮质醇测量可以作为一种有用的工具，用于观察皮质醇昼夜节律，并在CS患者治疗期间确定甲吡酮的剂量和给药时间。
