Cerina Vatroslav, Kruljac Ivan, Radosevic Jelena Marinkovic, Kirigin Lora Stanka, Stipic Darko, Pecina Hrvoje Ivan, Vrkljan Milan
From the Department of Neurosurgery (VC, DS), Department of Radiology (HIP), University Hospital Center "Sestre Milosrdnice," and Department of Endocrinology (IK, JMR, LK, MV), Diabetes and Metabolic Diseases "Mladen Sekso," University Hospital Center "Sestre Milosrdnice," University of Zagreb Medical School, Zagreb, Croatia.
Medicine (Baltimore). 2016 Mar;95(9):e2898. doi: 10.1097/MD.0000000000002898.
The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The addition of baseline LH to CORT3, increased sensitivity to 100.0%, specificity to 88.9%, PPV to 90.4%, and NPV to 100.0%. Besides CORT3, tumor size, thyroid hormones, and gonadotropins can serve as predictors of AI. LH in postmenopausal female patients with NPA has similar diagnostic accuracy as CORT3. Further studies are needed in order to validate the scoring system proposed by this study.
胰岛素耐量试验(ITT)是垂体手术后诊断肾上腺皮质功能减退(AI)的金标准。ITT对患者来说体验不佳,需要密切的医疗监督,并且在几种合并症中属于禁忌。本研究的目的是分析肿瘤大小、缓解率、术前和术后早期的基线激素浓度是否可作为AI的预测指标,以提高早晨血清皮质醇的诊断准确性。这项前瞻性研究连续纳入了70例新诊断的垂体腺瘤患者。37例患者患有无功能垂体腺瘤(NPA),28例患有催乳素瘤,5例患有生长激素瘤。术前及术后第6天测量甲状腺素(T4)、促甲状腺激素(TSH)、催乳素、卵泡刺激素(FSH)、黄体生成素(LH)、睾酮和胰岛素样生长因子1(IGF-I)。术后第3天(CORT3)和术后第6天(CORT6)测量早晨血清皮质醇。术前测量肿瘤大小,并在术后3个月评估缓解情况。术后3至6个月进行ITT。48%的患者实现缓解,51%的患者发生AI。缓解率和肿瘤类型与AI无关。CORT3对AI的预测价值最佳(曲线下面积(AUC)为0.868,敏感性为82.4%,特异性为83.3%)。在多变量回归模型中,肿瘤大小、术前T4、术后T4和TSH也与AI相关。所有术前和术后变量(不包括血清皮质醇)的组合敏感性为75.0%,特异性为77.8%。将这些变量添加到模型中后,CORT3的预测能力显著提高(AUC为0.921,敏感性为94.1%,特异性为78.3%,阳性预测值为81.9%,阴性预测值为92.7%)。在仅包括患有NPA的女性患者的亚组分析中,LH与CORT3具有完全相同的预测价值。将基线LH添加到CORT3中,敏感性提高到100.0%,特异性提高到88.9%,阳性预测值提高到90.4%,阴性预测值提高到100.0%。除CORT外,肿瘤大小、甲状腺激素和促性腺激素可作为AI的预测指标。绝经后患有NPA的女性患者中的LH与CORT3具有相似的诊断准确性。需要进一步研究以验证本研究提出的评分系统。