van Veelen H, Willemse P H, Sleijfer D T, van der Ploeg E, Sluiter W J, Doorenbos H
Cancer Chemother Pharmacol. 1985;15(2):167-70. doi: 10.1007/BF00257530.
To investigate the mechanism of adrenal suppression by high-dose MPA, we performed direct and indirect stimulation tests in postmenopausal women with disseminated breast cancer who were receiving MPA and in a postmenopausal breast cancer control group. A partial adrenal insufficiency was found during Synacthen stimulation, confirmed by a slight increase of 11-desoxycortisol after metyrapone, despite a sufficient rise in ACTH levels. Peak levels of androstenedione and 17-OH progesterone after Synacthen correlated with those after metyrapone. Peak cortisol levels after Synacthen also correlated with the sum of cortisol and 11-desoxycortisol values after metyrapone, indicating the presence of a maximum adrenal response and a sufficient rise of endogenous ACTH after metyrapone. As the peak levels of cortisol and androstenedione were highly correlated with baseline values, a short Synacthen stimulation test may give a good indication as to whether adrenal suppression by MPA is adequate. The adrenal androgen androstenedione is the precursor of the main postmenopausal oestrogen, oestrone. In this way, adrenal suppression may constitute an important therapeutic effect of high-dose MPA.
为研究大剂量甲羟孕酮（MPA）导致肾上腺抑制的机制，我们对正在接受MPA治疗的绝经后转移性乳腺癌妇女以及绝经后乳腺癌对照组进行了直接和间接刺激试验。在促肾上腺皮质激素（Synacthen）刺激试验中发现了部分肾上腺功能不全，尽管促肾上腺皮质激素释放激素（ACTH）水平有足够升高，但在甲吡酮试验后11-脱氧皮质醇略有升高，证实了这一点。Synacthen刺激试验后雄烯二酮和17-羟孕酮的峰值水平与甲吡酮试验后的峰值水平相关。Synacthen刺激试验后皮质醇峰值水平也与甲吡酮试验后皮质醇和11-脱氧皮质醇值之和相关，表明存在最大肾上腺反应以及甲吡酮试验后内源性ACTH有足够升高。由于皮质醇和雄烯二酮的峰值水平与基线值高度相关，短时间的Synacthen刺激试验可能很好地表明MPA导致的肾上腺抑制是否充分。肾上腺雄激素雄烯二酮是绝经后主要雌激素雌酮的前体。通过这种方式，肾上腺抑制可能构成大剂量MPA的一项重要治疗效果。
