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Urinary melatonin-sulfate/cortisol ratio and the presence of prostate cancer: A case-control study.

ABSTRACT: The circadian-related hormones, melatonin and cortisol, have oncostatic and immunosuppressive properties. This study examined the relationship between these two biomarkers and the presence of prostate cancer. We measured their major metabolites in urine collected from 120 newly diagnosed prostate cancer patients and 240 age-matched controls from January 2011 to April 2014. Compared with patients with lower urinary melatonin-sulfate or melatonin-sulfate/cortisol (MT/C) ratio levels, those with above-median levels were significantly less likely to have prostate cancer (adjusted OR (aOR)?=?0.59, 95% CI?=?0.35-0.99; aOR?=?0.46, 95% CI: 0.27-0.77) or advanced stage prostate cancer (aOR?=?0.49, 95% CI?=?0.26-0.89; aOR?=?0.33, 95% CI?=?0.17-0.62). The combined effect of both low MT/C ratios and PSA levels exceeding 10?ng/ml was an 8.82-fold greater likelihood of prostate cancer and a 32.06-fold greater likelihood of advanced stage prostate cancer, compared to those with both high MT/C ratios and PSA levels less than 10?ng/ml. In conclusion, patients with high melatonin-sulfate levels or a high MT/C ratio were less likely to have prostate cancer or advanced stage prostate. Besides, a finding of a low MT/C ratio combined with a PSA level exceeding 10?ng/ml showed the greatest potential in detecting prostate cancer and advanced stage prostate cancer.

SUBMITTER: Tai SY

PROVIDER: S-EPMC4937372 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Urinary melatonin-sulfate/cortisol ratio and the presence of prostate cancer: A case-control study.

Tai Shu-Yu SY Huang Shu-Pin SP Bao Bo-Ying BY Wu Ming-Tsang MT

Scientific reports 20160708

The circadian-related hormones, melatonin and cortisol, have oncostatic and immunosuppressive properties. This study examined the relationship between these two biomarkers and the presence of prostate cancer. We measured their major metabolites in urine collected from 120 newly diagnosed prostate cancer patients and 240 age-matched controls from January 2011 to April 2014. Compared with patients with lower urinary melatonin-sulfate or melatonin-sulfate/cortisol (MT/C) ratio levels, those with ab ...[more]

PMID: 27387675

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Project description:Cirrhotic patients are susceptible to sepsis and critical illness-related corticosteroid insufficiency (CIRCI). Dehydroepiandrosterone sulfate (DHEAS) is a corticotropin-dependent adrenal androgen, which has immunostimulating and antiglucocorticoid effects. Considering the synchronized synthesis of cortisol and DHEAS and their opposing effects to each other, investigators have proposed measuring these two hormones as a ratio. Severe sepsis has been associated with low DHEAS, especially relative to high cortisol. Despite growing interest in the role of adrenal androgen replacement in critical illness, there have been no data about DHEAS and the DHEAS/cortisol ratio in patients with liver cirrhosis. We studied whether low concentrations of DHEAS and decreased DHEAS/cortisol ratio are associated with poor outcome in patients with liver cirrhosis and septic shock.We recruited 46 cirrhotic patients with septic shock, and 46 noncirrhotic counterparts matched by age and sex. We evaluated adrenal function using the short corticotropin stimulation test and analyzed the relation between DHEAS and cortisol.While the nonsurvivors in the cirrhotic group had significantly lower baseline DHEAS, lower baseline DHEAS/cortisol ratio, and reduced increments of both DHEAS and cortisol upon corticotropin stimulation, the survivors had lower baseline cortisol. Cirrhotic patients with lower DHEAS/cortisol ratio (<1.50) had higher levels of interleukin-6 and tumor necrosis factor alpha, higher Sequential Organ Failure Assessment scores, and higher rates of CIRCI and hospital mortality. Using the area under the receiver operating characteristic (AUROC) curve, both DHEAS and the DHEAS/cortisol ratio demonstrated a good discriminative power for predicting hospital survival (AUROC 0.807 and 0.925 respectively). The cirrhotic group had lower DHEAS and DHEAS/cortisol ratio but higher rates of CIRCI and hospital mortality, compared to the noncirrhotic group.There is dissociation between cortisol (increased) and DHEAS (decreased) in those cirrhotic patients who succumb to septic shock. Low DHEAS/cortisol ratios are associated with more severe diseases, inflammation, and CIRCI and can serve as a prognostic marker. More investigations are needed to evaluate the role of adrenal androgen in this clinical setting.

Project description:BackgroundIn Europe, synthetic corticosteroids are not allowed in animal breeding for growth-promoting purposes. Nevertheless, a high prevalence of non-compliant urine samples was recently reported for prednisolone, however, without any indication of unauthorized use. Within this context, 20β-dihydroprednisolone and the prednisolone/cortisol ratio have been suggested as potential tools to discriminate between exogenous and endogenous urinary prednisolone. In this study, the validity of these strategies was verified by investigating the plasma pharmacokinetic and urinary excretion profiles of relevant glucocorticoids in bovines, subjected to exogenous prednisolone treatment or tetracosactide hexaacetate administration to induce endogenous prednisolone formation. Bovine urine and plasma samples were analysed by liquid chromatography and mass spectrometry.ResultsBased on the plasma pharmacokinetics and urinary profiles, 20β-dihydroprednisolone was confirmed as the main prednisolone-derived metabolite, being detected in the biological fluids of all 12 bovines (plasma AUC0-inf of 121 h μg L-1 and urinary concentration > 0.695 μg L-1). However, this metabolite enclosed no potential as discriminative marker as no significant concentration differences were observed upon exogenous prednisolone treatment or tetracosactide hexaacetate administration under all experimental conditions. As a second marker tool, the prednisolone/cortisol ratios were assessed along the various treatments, taking into account that endogenous prednisolone formation involves the hypothalamic-pituitary-adrenal axis and is associated with an increased cortisol secretion. Significantly lower ratios were observed in case of endogenous prednisolone formation (i.e. ratios ranging from 0.00379 to 0.129) compared to the exogenous prednisolone treatment (i.e. ratios ranging from 0.0603 to 36.9). On the basis of these findings, a discriminative threshold of 0.260 was proposed, which allowed classification of urine samples according to prednisolone origin with a sensitivity of 94.2% and specificity of 99.0%.ConclusionThe prednisolone/cortisol ratio was affirmed as an expedient strategy to discriminate between endogenous and exogenous prednisolone in urine. Although the suggested threshold value was associated with high specificity and sensitivity, a large-scale study with varying experimental conditions is designated to optimize this value.

Dataset Information

Urinary melatonin-sulfate/cortisol ratio and the presence of prostate cancer: A case-control study.

Publications

Urinary melatonin-sulfate/cortisol ratio and the presence of prostate cancer: A case-control study.

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