促肾上腺皮质激素（ACTH）对酮康唑治疗 6 个月后的库欣病患者的生长激素释放肽-6（GHRP-6）的反应性增加：与 GH-释放肽-6（GHRP-6）的比较。

Adrenocorticotrophic hormone (ACTH) responsiveness to ghrelin increases after 6 months of ketoconazole use in patients with Cushing's disease: comparison with GH-releasing peptide-6 (GHRP-6).

机构信息

Division of Endocrinology, Universidade Federal de São Paulo, São Paulo, Brazil.

出版信息

Clin Endocrinol (Oxf). 2010 Jan;72(1):70-5. doi: 10.1111/j.1365-2265.2009.03618.x. Epub 2009 Apr 29.

DOI:10.1111/j.1365-2265.2009.03618.x

PMID:19453623

Abstract

BACKGROUND

In Cushing's disease (CD), adrenocorticotrophic hormone (ACTH)/cortisol responses to growth hormone secretagogues (GHS), such as ghrelin and GHRP-6, are exaggerated. The effect of clinical treatment of hypercortisolism with ketoconazole on ACTH secretion in CD is controversial. There are no studies evaluating ACTH/cortisol responses to GHS after prolonged ketoconazole use in these patients.

OBJECTIVE

To compare ghrelin- and GHRP-6-induced ACTH/cortisol release before and after ketoconazole treatment in patients with CD.

DESIGN/PATIENTS: Eight untreated patients with CD (BMI: 28.5 +/- 0.8 kg/m(2)) were evaluated before and after 3 and 6 months of ketoconazole treatment and compared with 11 controls (BMI: 25.0 +/- 0.8).

RESULTS

After ketoconazole use, mean urinary free cortisol values decreased significantly (before: 613.6 +/- 95.2 nmol/24 h; 3rd month: 170.0 +/- 27.9; 6th month: 107.9 +/- 30.1). The same was observed with basal serum cortisol (before: 612.5 +/- 69.0 nmol/l; 3rd month: 463.5 +/- 44.1; 6th month: 402.8 +/- 44.1) and ghrelin- and GHRP-6-stimulated peak cortisol levels (before: 1183.6 +/- 137.9 and 1045.7 +/- 132.4; 3rd month: 637.3 +/- 69.0 and 767.0 +/- 91.0; 6th month: 689.8 +/- 74.5 and 571.1 +/- 71.7 respectively). An increase in basal ACTH (before: 11.2 +/- 1.6 pmol/l; 6th month: 19.4 +/- 2.7) and in ghrelin-stimulated peak ACTH values occurred after 6 months (before: 59.8 +/- 15.4; 6th month: 112.0 +/- 11.2). GHRP-6-induced ACTH release also increased (before: 60.7 +/- 17.2; 6th month: 78.5 +/- 12.1), although not significantly.

CONCLUSIONS

The rise in basal ACTH levels during ketoconazole treatment in CD could be because of the activation of normal corticotrophs, which were earlier suppressed by hypercortisolism. The enhanced ACTH responses to ghrelin after ketoconazole in CD could also be due to activation of the hypothalamic-pituitary-adrenal axis and/or to an increase in GHS-receptors expression in the corticotroph adenoma, consequent to reductions in circulating glucocorticoids.

摘要

背景

在库欣病（CD）中，生长激素释放肽（GHS），如胃饥饿素和 GHRP-6，刺激促肾上腺皮质激素（ACTH）/皮质醇的反应被夸大。使用酮康唑治疗皮质醇增多症对 CD 中 ACTH 分泌的临床疗效存在争议。在这些患者中，尚无研究评估长期使用酮康唑后对 GHS 的 ACTH/皮质醇反应。

目的

比较 CD 患者在酮康唑治疗前后胃饥饿素和 GHRP-6 诱导的 ACTH/皮质醇释放。

设计/患者：8 例未经治疗的 CD 患者（BMI：28.5 +/- 0.8 kg/m2）在接受酮康唑治疗前和治疗 3 个月和 6 个月后进行评估，并与 11 名对照者（BMI：25.0 +/- 0.8）进行比较。

结果

酮康唑使用后，尿游离皮质醇值显著下降（治疗前：613.6 +/- 95.2 nmol/24 h；治疗 3 个月：170.0 +/- 27.9；治疗 6 个月：107.9 +/- 30.1）。血清基础皮质醇也是如此（治疗前：612.5 +/- 69.0 nmol/l；治疗 3 个月：463.5 +/- 44.1；治疗 6 个月：402.8 +/- 44.1）和胃饥饿素和 GHRP-6 刺激的皮质醇峰值水平（治疗前：1183.6 +/- 137.9 和 1045.7 +/- 132.4；治疗 3 个月：637.3 +/- 69.0 和 767.0 +/- 91.0；治疗 6 个月：689.8 +/- 74.5 和 571.1 +/- 71.7）。基础 ACTH 水平升高（治疗前：11.2 +/- 1.6 pmol/l；治疗 6 个月：19.4 +/- 2.7）和胃饥饿素刺激的 ACTH 峰值在 6 个月后增加（治疗前：59.8 +/- 15.4；治疗 6 个月：112.0 +/- 11.2）。GHRP-6 诱导的 ACTH 释放也增加（治疗前：60.7 +/- 17.2；治疗 6 个月：78.5 +/- 12.1），尽管不显著。