库欣病患者血浆19-羟雄烯二酮水平升高：促肾上腺皮质激素刺激和甲吡酮抑制作用

Elevated plasma 19-hydroxyandrostenedione levels in Cushing's disease: stimulation with ACTH and inhibition with metyrapone.

作者信息

Mune T, Morita H, Yasuda K, Murayama M, Yamakita N, Miura K

机构信息

Third Department of Internal Medicine, Gifu University School of Medicine, Japan.

出版信息

Clin Endocrinol (Oxf). 1993 Mar;38(3):265-72. doi: 10.1111/j.1365-2265.1993.tb01005.x.

DOI:10.1111/j.1365-2265.1993.tb01005.x

PMID:8384536

Abstract

OBJECTIVE

The regulation of 19-hydroxyandrostenedione secretion has been suggested to be under the control of both the ACTH-adrenal axis and renin-angiotensin system. We undertook the present study to evaluate the effect of the chronic excess of ACTH, or the short-term excess of ACTH due to metyrapone, on 19-hydroxyandrostenedione secretion in patients with Cushing's disease.

DESIGN AND PATIENTS

We measured plasma 19-hydroxyandrostenedione levels simultaneously with plasma delta 4-androstenedione, corticosterone, 11-deoxycorticosterone, aldosterone and cortisol levels after HPLC separation in 13 patients with Cushing's disease under basal conditions and during a dexamethasone suppression test or metyrapone test. Seven patients with Cushing's syndrome due to adrenal adenoma were used for comparison.

RESULTS

The basal levels of 19-hydroxyandrostenedione in Cushing's disease were elevated (mean +/- SD; 323 +/- 193 pmol/l, n = 13), while those in Cushing's syndrome due to adrenal adenoma were low (92 +/- 24 pmol/l, n = 7), compared to those in normal subjects (117 +/- 33 pmol/l, n = 54). The basal levels of delta 4-androstenedione were mildly elevated in Cushing's disease (9.0 +/- 6.5 vs 3.6 +/- 2.6 nmol/l of normal subjects) but not in Cushing's syndrome due to adrenal adenoma (3.1 +/- 3.0 nmol/l). In the overnight 8 mg dexamethasone suppression test in Cushing's disease (n = 12), plasma levels of 19-hydroxyandrostenedione and delta 4-androstenedione decreased from 277 +/- 172 to 156 +/- 99 pmol/l and from 9.2 +/- 6.8 to 4.7 +/- 3.4 nmol/l, respectively, whereas the overnight 1 mg dexamethasone suppression test did not induce significant changes. Metyrapone administration in Cushing's disease (n = 9) increased plasma delta 4-androstenedione level from 9.5 +/- 6.7 to 47.2 +/- 28.1 nmol/l, but decreased plasma 19-hydroxyandrostenedione level from 301 +/- 196 to 196 +/- 105 pmol/l.

CONCLUSIONS

These data indicate that plasma levels of 19-hydroxyandrostenedione in patients with Cushing's disease are elevated due to chronic ACTH excess, and that metyrapone can inhibit 19-hydroxylation in humans.

摘要

目的

有研究表明，19-羟雄烯二酮的分泌受促肾上腺皮质激素-肾上腺轴和肾素-血管紧张素系统的共同调控。我们开展了本研究，以评估库欣病患者中促肾上腺皮质激素长期过量或因甲吡酮导致的促肾上腺皮质激素短期过量对19-羟雄烯二酮分泌的影响。

设计与患者

我们在13例库欣病患者的基础状态下以及地塞米松抑制试验或甲吡酮试验期间，通过高效液相色谱分离后，同时测定血浆19-羟雄烯二酮水平以及血浆δ4-雄烯二酮、皮质酮、11-脱氧皮质酮、醛固酮和皮质醇水平。选取7例肾上腺腺瘤所致库欣综合征患者作为对照。

结果

与正常受试者（117±33 pmol/L，n = 54）相比，库欣病患者的19-羟雄烯二酮基础水平升高（均值±标准差；323±193 pmol/L，n = 13），而肾上腺腺瘤所致库欣综合征患者的该水平较低（92±24 pmol/L，n = 7）。库欣病患者的δ4-雄烯二酮基础水平轻度升高（9.0±6.5 vs正常受试者的3.6±2.6 nmol/L），但肾上腺腺瘤所致库欣综合征患者则未升高（3.1±3.0 nmol/L）。在库欣病患者（n = 12）的过夜8 mg地塞米松抑制试验中，血浆19-羟雄烯二酮和δ4-雄烯二酮水平分别从277±172降至156±99 pmol/L以及从9.2±6.8降至4.7±3.4 nmol/L，而过夜1 mg地塞米松抑制试验未引起显著变化。在库欣病患者（n = 9）中给予甲吡酮后，血浆δ4-雄烯二酮水平从9.5±6.7升至47.2±28.1 nmol/L，但血浆19-羟雄烯二酮水平从301±196降至196±105 pmol/L。