Receiver Operating Characteristic Curve Method Research Articles

The value of corticotropin-releasing hormone (CRH) test for differential diagnosis of Cushing’s syndrome

Diagnosis and differential diagnosis of Cushing's syndrome (CS) remain considerable challenge in endocrinology. For more than 20 years, CRH has been widely used as differential diagnostic test. Following the CRH administration, the majority of patients with ACTH secreting pituitary adenoma show a significant rise of plasma cortisol and ACTH, whereas those with ectopic ACTH secretion characteristically do not. The aim of our study was to assess the value of CRF test for differential diagnosis of CS using the ROC (receiver operating characteristic) curve method. A total of 30 patients with CS verified by pathological examination and postoperative testing were evaluated. CRH test was performed within diagnostic procedures. ACTH secreting pituitary adenoma was found in 18, ectopic ACTH secretion in 3 and cortisol secreting adrenal adenoma in 9 of all patients with CS. Cortisol and ACTH were determined -15.0, 15, 30, 45, 60, 90 and 120 min. after i.v. administration of 100 microg of ovine CRH. Cortisol and ACTH were determined by commercial RIA. Statistical data processing was done by ROC curve analysis. Due to small number, the patients with ectopic ACTH secretion were excluded from test evaluation by ROC curve method. In evaluated subgroups, basal cortisol was (1147.3 +/- 464.3 vs. 1589.8 +/- 296.3 vs. 839.2 +/- 405.6 nmol/L); maximal stimulated cortisol (1680.3 +/- 735.5 vs. 1749.0 +/- 386.6 vs. 906.1 +/- 335.0 nmol/L); and maximal increase as a percent of basal cortisol (49.1 +/- 36.9 vs. 9.0 +/- 7.6 vs. 16.7 +/- 37.3%). Consequently, basal ACTH was (100.9 +/- 85.0 vs. 138.0 +/- 123.7 vs. 4.8 +/- 4.3 pg/mL) and maximal stimulated ACTH (203.8 +/- 160.1 vs. 288.0 +/- 189.5 vs. 7.4 +/- 9.2 pg/mL). For cortisol, determination area under ROC curve was 0.815 +/- 0.083 (CI 95% 0.652-0.978). For cortisol increase cut-off level of 20%, test sensitivity was 83%, with specificity of 78%. For ACTH, determination area under ROC curve was 0.637 +/- 0.142 (CI 95% 0.359-0.916). For ACTH increase cut-off level of 30%, test sensitivity was 70%, with specificity of 57%. Determination of cortisol and ACTH levels in CRH test remains reliable tool in differential diagnosis of Cushing's syndrome.

Finite Mixture Models in Assessing Anti-thyroglobulin Antibody Positivity as a Marker of Chronic Thyroiditis

Positivity of anti-thyroglobulin antibody (TgAb) is one of the markers of chronic thyroiditis (Hashimoto disease). From 2000 to 2003, a thyroid disease prevalence study was conducted at the Radiation Effects Research Foundation, in Hiroshima and Nagasaki. Utilizing the study's results, we show that via EM algorithm log-transformed TgAb level is compatible with a two-component mixture normal distribution, with the smaller normal distribution corresponding to the TgAb negative group but the larger distribution not necessarily corresponding to the TgAb positive group. A subject is determined to be TgAb positive if TgAb level is greater than a given cutoff. We compared the cutoff values from population-based methods and the laboratory method. The population-based methods consist of a simple method, a receiver operating characteristic (ROC) curve method, and a minimum misclassification rate (MMR) method. The simple method is used to determine positivity from only TgAb negative populations. Since the ROC curve and MMR methods are valid only when TgAb positivity and negativity are known but the simple method is valid only when TgAb negativity is known, the simple method was deemed useful for determining the cutoff in our data. In comparison with the simple, population-based method, we show that the cutoff from the laboratory method is appropriate and that the TgAb positive rates from various methods are approximately equal. With the two-component mixture normal distribution in TgAb level, our simple population-based method for determination of cutoff is another more practical example of handling the clinical measurement than the method given in Thompson et al. (Applied Statistics 1998).

The value of preoperative platelet count in the prediction of cervical involvement and poor prognostic variables in patients with endometrial carcinoma

Objective(s). To evaluate the relationship between preoperative platelet counts and prognostic factors extensively, among endometrial cancer patients, especially with respect to cervical involvement. Methods. One-hundred fifty-five patients with endometrial carcinoma, who underwent surgery as the initial treatment consisting peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, systematic pelvic-paraaortic lymphadenectomy, and omentectomy were retrospectively analyzed. Results. There were no differences with respect to age, histological type (endometrioid vs. non-endometrioid), depth of myometrial invasion, peritoneal cytology, LVSI, and lymphatic metastasis. However, advanced stage (stages III and IV), poorly differentiated tumor grade (grade 3), the presence of cervical and adnexal involvements were associated with significantly higher median preoperative platelet counts. Accepting 325.000/μl platelet count as a threshold value, multivariate analysis revealed cervical involvement ( P = 0.008; OR = 1.84, 95% CI:1.17–2.89) and presence of high grade histology ( P = 0.014; OR = 2.23, 95% CI:1.18–4.23, for grade 3 disease) to be significantly associated with higher platelet count. At a cut-off value of 326.000/μl, 42.3% sensitivity and 82.8% specificity for the prediction of cervical involvement was observed under receiver operator characteristic curve method. Conclusion(s). Higher preoperative platelet counts, even in conditions with normal range (150.000–400.000/μl), may reflect poor prognostic factors such as cervical involvement and high grade among patients with endometrial carcinoma. Also, the higher platelet count should be taken into consideration for the necessity of radical hysterectomy.

The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease

Taking advantage of the over-expression of V3 receptors in adenomatous corticotroph cells, we evaluated the response to the vasopressin agonist desmopressin in 22 patients operated on for Cushing's disease, with a mean follow-up of 4.5 years. Twenty-two patients (17 women) operated on for Cushing's disease with a follow-up >2 years (median, 48; range, 24-141 months) underwent one desmopressin test (10 microg i.v. bolus) 3-6 months postoperatively. Twelve were in remission (R group), five had immediate failure (IF) after surgery and five had late recurrence (LR). Both ACTH and cortisol peaks after desmopressin were significantly lower in the R group than in the LR group (P=0.003 and P=0.013 respectively). The receiver operator characteristic curve method defined an ACTH peak threshold > or =22 pg/ml or ACTH rise > or =35%; cortisol peak > or =350 nmol/l or cortisol rise > or =14%. None of twelve patients in remission had ACTH or cortisol peaks above these thresholds vs three of five patients from the LR group and five of five in the IF group. On the basis of ACTH or cortisol peaks respectively, the desmopressin test was predictive of a later recurrence with a positive predictive value of 100% or 80% respectively, and a negative predictive value of 92%. Sensitivity and specificity were 80% and 100% respectively based on ACTH peak, and 80% and 92% respectively based on cortisol peak. In this first long-term study, a marked response of ACTH or cortisol to desmopressin was predictive of a later recurrence with good specificity and sensitivity.

Optimal Cutoff of the Hybrid Capture II Human Papillomavirus Test for Self-Collected Vaginal, Vulvar, and Urine Specimens in a Colposcopy Referral Population

To estimate the optimal relative light unit ratio, as a measure of viral load, of the Hybrid Capture II human papillomavirus (HPV) test in self-collected specimens for detecting cervical intraepithelial neoplasia (CIN). Two hundred women referred for colposcopy with abnormal cytologic, self-collected vaginal and vulvar swabs and urine for HPV testing. The receiver operating characteristic (ROC) curve method was used to estimate optimal cutoffs for the Hybrid Capture II test. The reference standard was colposcopy, with directed biopsy as required. The estimated optimal cutoffs of the relative light unit ratio for detecting CIN 2 or higher for urine, vulvar, and vaginal samples gave sensitivities of 72.4%, 82.8%, and 89.0% and specificities of 57.0%, 52.1%, and 55.9%, respectively. At the manufacturer's recommended 1.0 cutoff, sensitivities were 44.8%, 62.1%, and 86.2% for urine, vulvar, and vaginal samples, with specificities of 69.7%, 62.7%, and 53.5%, respectively. The likelihood ratios (likelihood of being truly positive after a positive test result) were similar for the optimal and the 1.0 cutoff. The ROC curve methods did not improve the overall diagnostic accuracy of the Hybrid Capture II test compared with the 1.0 relative light unit ratio cutoff.

Prediction of invasive activities in hepatocellular carcinomas with special reference to alpha-fetoprotein and des-gamma-carboxyprothrombin.

Hepatocellular carcinoma (HCC) is one of the world's major malignancies, especially in Asian countries. To improve the prognosis of HCC, it is essential to predict its invasive behavior in both intra- and extra-hepatic modalities. For this purpose, we examined the predictive values of two tumor markers, alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP). 194 HCC cases at the National Cancer Center Hospital were selected from the Pathology Records. Detailed information regarding the existence of extra-hepatic venous invasion (EHVI) at the portal vein and intra-hepatic multiple malignant tumors (IHMTs) were collected and combined with the preoperative AFP and DCP testing results. Furthermore, information about the viral infection status such as HBs antigen positive or HCV antibody positive or no viral hepatitis was obtained. The information was analyzed by the ROC (Receiver Operating Characteristic Curve) method. and In both the EHVI group and the IHMT group, all the combinations except the HCV-positive group of IHMT revealed a tendency for DCP to offer better diagnostic accuracies, although this was statistically significant only in the HBs-positive group of IHMT. This result indicates either (1). that in a strict sense, DCP is not necessarily better than AFP at predicting the invasive characteristics or (2). that DCP is better than AFP at reflecting the invasive characteristics of HCC although not statistically significant. In either situation, from a long-term viewpoint, it is advisable to find a new marker or to re-evaluate the existing markers in order to predict the invasive characteristics more accurately.