Background: We evaluated the discriminating capacity of the indole markers urinary 5-hydroxyindoleacetic acid (5-HIAA), urinary serotonin, and platelet serotonin in the diagnosis of carcinoid tumors.
Methods: Indole markers were measured in 688 patients with suspected carcinoid disease. The initial values of indole markers from patients in whom a carcinoid tumor was confirmed during follow-up (n = 98) were used for ROC analysis. Two groups served as reference populations. The first consisted of 45 healthy individuals (“healthy controls”). The second was a random sample of 40 patients, drawn from the 590 (688 minus 98) patients with carcinoid-like symptoms but without a carcinoid tumor (“clinically suspected patients”).
Results: ROC curve analysis showed platelet serotonin to have the highest discriminating capacity, especially in foregut carcinoids. Cutoff values for platelet serotonin obtained from ROC analysis with healthy controls as reference group (5.4 nmol/109 platelets) gave a sensitivity of 74%, specificity of 91%, positive predictive value of 63%, and negative predictive value of 95% when applied to the initial 688 patients. Using the cutoff value with the clinically suspected patients as the reference group (9.3 nmol/109 platelets) gave a sensitivity of 63%, specificity of 99%, positive predictive value of 89%, and negative predictive value of 93%. Indole markers were increased in 169 (25%) of 688 patients. In 76 (45%) of these 169 patients, a carcinoid tumor was present. Slight increases of markers were associated with non-carcinoid neuroendocrine tumors, non-neuroendocrine tumors, and disturbed bowel motility.
Conclusions: ROC curve analysis shows that platelet serotonin is the most discriminating indole marker for the diagnosis of carcinoid tumors. Platelet serotonin especially improves the diagnosis of carcinoids producing small amounts of serotonin.
Patients with endometrial, ovarian, and vulvar cancer have increased tryptophan degradation compared to controls resulting in higher serum kynurenine concentrations and a higher kyn/trp ratio. Our results suggest that IDO-induced immune escape may play an important role in these gynecologic cancers.
BACKGROUND
Determination of the aldosterone-to-renin ratio (ARR) in blood is the preferred screening test for primary aldosteronism. Renin can be measured as the plasma renin activity (PRA) or the plasma renin concentration (PRC). Consequently, the ARR can be measured either based on the PRA (ARRpra) or based on the PRC (ARRprc). In contrast with the ARRpra, the data on reference values for the ARRprc are limited. Moreover, whether the ARRpra or ARRprc is affected by variations in salt intake is unknown.
METHODS
We measured the PRA, the PRC, and serum aldosterone in 100 normotensive individuals between 20 and 70 years of age before and after a 3-day oral sodium-loading test (SLT). Participants were stratified according to age and sex. Data are presented as the median and interquartile range (IQR).
RESULTS
Urinary sodium excretion after the SLT was ≥200 mmol/24 h in all participants. Serum aldosterone, PRA, and PRC values were significantly reduced after the SLT. PRC and PRA results were highly correlated [Spearman rank correlation rs = 0.80 and 0.74 before and after SLT, respectively; P < 0.001 for both]. The central 95% reference intervals for ARRpra before and after SLT were 0.07–1.45 h−1 and 0.06–1.84 h−1, respectively. The corresponding reference intervals for ARRprc were 4.1–81.3 pmol/ng and 3.9–74.8 pmol/ng. The median ARRprc decreased after the SLT from 19.5 pmol/ng (IQR, 13.0–29.4 pmol/ng) to 18.6 pmol/ng (IQR, 9.4–27.1 pmol/ng) (P = 0.005), whereas the median ARRpra did not change (P = 0.12). Both the ARRprc and ARRpra at baseline were higher in women than in men, whereas no sex difference was observed after sodium loading.
CONCLUSIONS
We present reference values for the ARRprc for healthy individuals. The ARR is affected to a variable degree by sex and sodium intake.
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