Background: Salivary cortisol is increasingly used to assess patients with suspected hypo-and hypercortisolism. This study established disease-specific reference ranges for an automated electrochemiluminescence immunoassay (ECLIA). Methods: Unstimulated saliva from 62 patients with hypothalamic-pituitary disease was collected at 0800 h. A peak serum cortisol level below 500 nmol/l during the insulin tolerance test (ITT) was used to identify hypocortisolism. Receiver-operating characteristic (ROC) analysis allowed establishment of lower and upper cutoffs with at least 95% specificity for adrenal insufficiency and adrenal sufficiency. Saliva from 40 patients with confirmed hypercortisolism, 45 patients with various adrenal masses, and 115 healthy subjects was sampled at 2300 h and after low-dose dexamethasone suppression at 0800 h. ROC analysis was used to calculate thresholds with at least 95% sensitivity for hypercortisolism. Salivary cortisol was measured with an automated ECLIA. Results: When screening for secondary adrenal insufficiency, a lower cutoff of 3.2 nmol/l and an upper cutoff of 13.2 nmol/l for unstimulated salivary cortisol allowed a highly specific diagnosis (i.e. similar to the ITT result) in 26% of patients. For identification of hypercortisolism, cutoffs of 6.1 nmol/l (sensitivity 95%, specificity 91%, area under the curve (AUC) 0.97) and 2.0 nmol/l (sensitivity 97%, specificity 86%, AUC 0.97) were established for salivary cortisol at 2300 h and for dexamethasonesuppressed salivary cortisol at 0800 h. Conclusions: The newly established thresholds facilitated initial screening for secondary adrenal insufficiency and allowed excellent identification of hypercortisolism. Measurement by an automated immunoassay will allow broader use of salivary cortisol as a diagnostic tool.

Physical exercise may lead to relevant changes in metanephrine and normetanephrine and should therefore be avoided prior to sampling. Although effects of age, sex and BMI were small, these variables should be considered when interpreting biochemical results. Blood should be taken in the supine position, and samples should be immediately centrifuged and stored at 4 degrees C to improve stability.

We sought to identify circulating microRNAs as biomarkers of prevalent or incident diabetes. In a pilot study of 18 sex- and age-matched patients with metabolic syndrome, nine of whom developed diabetes during 6 years of follow-up, an array of 372 microRNAs discovered significantly elevated serum levels of microRNAs -122, -192, -194, and -215 in patients who developed diabetes mellitus type 2 (T2DM). In two cross-sectional validation studies, one encompassing sex- and age-matched groups of patients with T2DM, impaired fasting glucose (IFG) and euglycemic controls (n = 43 each) and the other 53 patients with type 1 diabetes and 54 age- and BMI-matched euglycemic controls, serum levels of miR-192, miR-194, and mi215 were significantly higher in diabetic subjects than in probands with euglycemia or IFG. In a longitudinal study of 213 initially diabetes-free patients of whom 35 developed diabetes during 6 years of follow-up, elevated serum levels of microRNAs 192 and 194 were associated with incident T2DM, independently of fasting glucose, HbA1c and other risk factors. Serum levels of miR-192 and miR-194 were also elevated in diabetic Akt2 knockout mice compared to wild type mice. In conclusion, circulating microRNAs -192 and -194 are potential biomarkers for risk of diabetes.

Previous research suggests that patients with obsessive-compulsive disorder (OCD), particularly checkers, display an inflated sense of responsibility. For the present study, we tested whether memory confidence in OCD is reduced under conditions of heightened responsibility and/or reflects poor memory vividness. A computerized task designed to modulate perceived responsibility was administered to 26 OCD patients (12 checkers) and 21 healthy controls. In the experimental condition (high responsibility), participants had to allocate daily medications to ten fictive patients in a hospital emergency ward, whereas in the control condition (low responsibility) participants had to allocate bath essences for ten hotel guests. Participants' response time and accuracy were recorded as well as their memory confidence, memory vividness, and subjective success. Irrespective of the condition, OCD patients performed as accurately as healthy controls, but appraised their performance as worse than that of controls. Memory confidence was decreased in patients, particularly checkers. No group differences emerged on vividness, and none of the effects were moderated by the condition (high versus low responsibility). The relationship between responsibility and OCD behavior is complex. Results suggest metamemory problems in OCD checkers, even when induced responsibility is low. The findings speak against "cold" memory deficits in OCD, as patients did not differ from controls on accuracy, reaction time, or vividness. Future research should focus on idiosyncratic beliefs and scenarios that inflate responsibility and elicit cognitive biases.

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