Giordano R, Pellegrino M, Oleandri S, Baldi M, Balbo M, Laureti S, Falorni A, Ghigo E, Arvat E
Division of Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy.
J Clin Endocrinol Metab. 2004 Feb;89(2):675-80. doi: 10.1210/jc.2003-030814.
Autoimmune polyglandular syndromes are fairly common diseases that are classified into four constellations based on the clinical clustering of the various component diseases. In types 1, 2, and 4, primary adrenal insufficiency due to an autoimmune process is usually present, but its diagnosis is often delayed because it is difficult to detect in a subclinical phase. It is widely accepted that the classical dose of 250 microg ACTH(1-24) is supramaximal, whereas 0.06 microg has been shown to be one of the lowest ACTH doses that is able to stimulate adrenal secretion in normal young subjects. The aim of this study was to clarify the sensitivity and maximal secretory response of the adrenal gland to ACTH in a group of patients with at least two autoimmune diseases, without clinical signs and symptoms of overt or subclinical hypocortisolism. Cortisol (F), aldosterone (A), and dehydroepiandrosterone (DHEA) responses to the sequential administration of very low and supramaximal ACTH(1-24) doses [0.06 microg followed by 250 microg ACTH(1-24) i.v. at 0 and +60 min] were studied in 18 patients with at least two autoimmune diseases (AP; age, 20-40 yr; body mass index, 22-26 kg/m(2)). The results in the patients were compared with the results recorded in 12 normal age-matched control subjects (CS; age, 22-34 yr; body mass index, 20-25 kg/m(2)). At baseline, ACTH levels in AP were within the normal range but higher (P < 0.05) than in CS, whereas F, A, DHEA, urinary-free F, and plasma renin activity were similar in both groups. F, A, and DHEA responses to ACTH were dose dependent in both groups. However, in AP, F, A, and DHEA levels showed no response to the 0.06- micro g ACTH dose, which, in turn, elicited clear responses (P < 0.01) in CS. On the other hand, F, A, and DHEA responses to 250 microg ACTH in AP were not different from those in CS. In conclusion, patients with autoimmune diseases who displayed a normal basal adrenal function showed a loss of F, A, and DHEA response to the very low ACTH dose, although they were normal responders to the high ACTH dose. These data are likely to indicate that a reduced sensitivity to ACTH in all adrenal zones occurs in patients with different types of autoimmune disease.
自身免疫性多内分泌腺综合征是相当常见的疾病，根据各种组成疾病的临床聚类分为四种类型。在1型、2型和4型中，通常存在由于自身免疫过程导致的原发性肾上腺功能不全，但其诊断往往延迟，因为在亚临床阶段很难检测到。人们普遍认为，250微克促肾上腺皮质激素（1-24）的经典剂量是超最大剂量，而0.06微克已被证明是能够刺激正常年轻受试者肾上腺分泌的最低促肾上腺皮质激素剂量之一。本研究的目的是阐明一组患有至少两种自身免疫性疾病、无明显或亚临床皮质醇增多症临床体征和症状的患者肾上腺对促肾上腺皮质激素的敏感性和最大分泌反应。在18例患有至少两种自身免疫性疾病（AP；年龄20-40岁；体重指数22-26kg/m²）的患者中，研究了皮质醇（F）、醛固酮（A）和脱氢表雄酮（DHEA）对依次静脉注射极低和超最大剂量促肾上腺皮质激素（1-24）[0分钟和+60分钟时分别静脉注射0.06微克，随后静脉注射250微克促肾上腺皮质激素（1-24）]的反应。将患者的结果与12名年龄匹配的正常对照受试者（CS；年龄22-34岁；体重指数20-25kg/m²）记录的结果进行比较。在基线时，AP患者的促肾上腺皮质激素水平在正常范围内，但高于CS患者（P<0.05），而两组的F、A、DHEA、尿游离F和血浆肾素活性相似。两组中F、A和DHEA对促肾上腺皮质激素的反应均呈剂量依赖性。然而，在AP患者中，F、A和DHEA水平对0.06微克促肾上腺皮质激素剂量无反应，而该剂量在CS患者中引起明显反应（P<0.01）。另一方面，AP患者对250微克促肾上腺皮质激素的F、A和DHEA反应与CS患者无差异。总之，基础肾上腺功能正常的自身免疫性疾病患者对极低剂量促肾上腺皮质激素的F、A和DHEA反应丧失，尽管他们对高剂量促肾上腺皮质激素反应正常。这些数据可能表明，不同类型自身免疫性疾病患者的所有肾上腺区域对促肾上腺皮质激素的敏感性降低。
