Castro Margaret, Elias Lucila L K, Elias Paula C L, Moreira Ayrton C
Division of Endocrinology, Department of Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
Clin Endocrinol (Oxf). 2003 Dec;59(6):800-5. doi: 10.1046/j.1365-2265.2003.01908.x.
A dose-response study with different doses of dexamethasone (dex) to assess the corticotrophic resistance in Cushing's disease (CD) using salivary cortisol as an end point has not yet been evaluated. We also reported our experience with salivary cortisol compared to plasma cortisol determination during dex suppression test (DST) and after ovine corticotrophin release hormone (oCRH) test in the differential diagnosis of Cushing's syndrome (CS).
We studied 46 patients with CS, including 28 patients with CD, 16 with adrenal disease and two with occult ectopic adrenocorticotropic hormone (ACTH) tumours. Salivary cortisol was compared to plasma cortisol and ACTH during a DST 2 mg for 2 days, 8 mg for 2 days and 24 mg for 1 day, and after oCRH test.
We observed a dose-dependent suppression of salivary cortisol, plasma cortisol and ACTH in CD patients. Salivary cortisol presented a higher percentage of suppression than plasma cortisol: 42% vs. 15% (P < 0.002), 82% vs. 67% (P < 0.002) and 90% vs. 83% (P < 0.03) after 2, 8 and 24 mg/day dex, respectively. The lowest percentage of suppression was observed for plasma ACTH. The parallelism of these lines identified that the criterion of 65% suppression of salivary cortisol corresponding to 50% suppression of plasma cortisol after 8 mg/day for 2 days is consistent with CD. The sensitivity and specificity using 50% suppression for plasma cortisol were 81% and 83%, respectively, for 8 mg DST. Using the criterion of 65% suppression of salivary cortisol, the sensitivity and specificity were 86% and 100%, respectively, for 8 mg DST. After oCRH test the sensitivity and specificity were 86% and 91%, respectively, for ACTH, 100% and 64%, respectively, for plasma cortisol and 93% and 91%, respectively, (20% of increment) or 86% and 100%, respectively, (35% increment) for salivary cortisol.
In conclusion, salivary cortisol presents more profound suppression than plasma cortisol or ACTH in a dose-response pattern after different doses of dex in patients with CD. In addition, our data suggest that measurement of salivary cortisol might improve the DST as compared to plasma cortisol in the differential diagnosis of CS.
尚未有研究使用不同剂量的地塞米松(dex)进行剂量反应研究,以唾液皮质醇作为终点来评估库欣病(CD)中的促肾上腺皮质激素抵抗。我们还报告了在库欣综合征(CS)的鉴别诊断中,与地塞米松抑制试验(DST)期间及羊促肾上腺皮质激素释放激素(oCRH)试验后测定血浆皮质醇相比,我们在唾液皮质醇方面的经验。
我们研究了46例CS患者,包括28例CD患者、16例肾上腺疾病患者和2例隐匿性异位促肾上腺皮质激素(ACTH)肿瘤患者。在为期2天给予2mg、为期2天给予8mg和为期1天给予24mg的DST期间以及oCRH试验后,对唾液皮质醇与血浆皮质醇和ACTH进行了比较。
我们观察到CD患者的唾液皮质醇、血浆皮质醇和ACTH呈剂量依赖性抑制。唾液皮质醇的抑制百分比高于血浆皮质醇:在每天给予2mg、8mg和24mg地塞米松后,抑制百分比分别为42%对15%(P<0.002)、82%对67%(P<0.002)和90%对83%(P<0.03)。血浆ACTH的抑制百分比最低。这些曲线的平行性表明,在每天给予8mg、持续2天的情况下,唾液皮质醇抑制65%对应血浆皮质醇抑制50%的标准与CD相符。对于8mg的DST,以血浆皮质醇抑制50%为标准,敏感性和特异性分别为81%和83%。以唾液皮质醇抑制65%为标准,对于8mg的DST,敏感性和特异性分别为86%和100%。oCRH试验后,ACTH的敏感性和特异性分别为86%和91%,血浆皮质醇分别为100%和64%,唾液皮质醇分别为93%和91%(增加20%)或86%和100%(增加35%)。
总之,在CD患者中,不同剂量地塞米松后的剂量反应模式中,唾液皮质醇的抑制比血浆皮质醇或ACTH更显著。此外,我们的数据表明,在CS的鉴别诊断中,与血浆皮质醇相比,唾液皮质醇的测量可能会改善DST。