Geffner M E, Lippe B M, Kaplan S A, Itami R M
J Clin Endocrinol Metab. 1982 Jul;55(1):56-60. doi: 10.1210/jcem-55-1-56.
The first step in the stimulatory action of most polypeptide hormones, including ACTH, is interaction with a specific target organ plasma membrane receptor. Theophylline, a nonspecific stimulus of several endocrine processes, does so presumably by circumventing the receptor step and directly increasing cAMP by inhibiting phosphodiesterase-mediated hydrolysis. Five patients with adrenal insufficiency, documented by a lack of cortisol secretion in response to exogenous ACTH, underwent a 4-h iv infusion of theophylline. In three of the five individuals, a significant concentration of cortisol was measured in serum for the first time. The patients who responded included one patient with the syndrome of ACTH insensitivity, one with ACTH deficiency, and one with idiopathic primary adrenal failure. Two patients with autoimmune adrenalitis failed to respond to theophylline, although one was tested very early in the course of her disease. We also noted that theophylline stimulated renin secretion and, in one patient with an intact zona glomerulosa, evoked a secondary rise in aldosterone equal to that produced by diuresis and upright posture. These studies suggest that the preservation of cortisol responsiveness to theophylline, after the loss of sensitivity to ACTH, may be relate to either the duration of the adrenal insufficiency or to the etiological mechanism. Patients with autoimmune adrenalitis may undergo more rapid and complete adrenocortical destruction, therapy losing sensitivity to both ACTH and theophylline, whereas patients with insufficient or ineffective ACTH stimulation may have receptor failure before the loss of intracellular function. Thus, responsiveness to iv theophylline may serve not only as a probe of potential adrenocortical reserve, but also as an indicator of pathogenesis.
包括促肾上腺皮质激素（ACTH）在内的大多数多肽激素的刺激作用的第一步，是与特定靶器官的质膜受体相互作用。氨茶碱是几种内分泌过程的非特异性刺激物，它可能通过绕过受体步骤并通过抑制磷酸二酯酶介导的水解直接增加环磷酸腺苷（cAMP）来实现这一点。五名肾上腺功能不全患者，经对外源性ACTH无皮质醇分泌反应证实，接受了4小时的氨茶碱静脉输注。在这五名个体中的三名中，首次在血清中检测到显著浓度的皮质醇。有反应的患者包括一名ACTH不敏感综合征患者、一名ACTH缺乏患者和一名特发性原发性肾上腺功能衰竭患者。两名自身免疫性肾上腺炎患者对氨茶碱无反应，尽管其中一名患者在疾病过程中很早便接受了检测。我们还注意到氨茶碱刺激肾素分泌，并且在一名球状带完整的患者中，引发了醛固酮的继发性升高，其幅度与利尿和直立姿势所产生的升高幅度相当。这些研究表明，在对ACTH失去敏感性后，皮质醇对氨茶碱的反应性得以保留，可能与肾上腺功能不全的持续时间或病因机制有关。自身免疫性肾上腺炎患者可能会经历更快速和完全的肾上腺皮质破坏，从而对ACTH和氨茶碱均失去敏感性，而ACTH刺激不足或无效的患者可能在细胞内功能丧失之前就存在受体功能障碍。因此，对静脉注射氨茶碱的反应性不仅可作为潜在肾上腺皮质储备的一种检测手段，还可作为发病机制的一个指标。
