Objective: The prognostic/diagnostic biomarker copeptin, an arginine vasopressin surrogate, reflects physical stress. Whether copeptin concentration increases upon psychological stress is unknown. We investigated psychological stress effects on copeptin secretion in healthy volunteers and patients with central diabetes insipidus (DI). Design: A prospective observational study was conducted to study the relation between copeptin concentration and psychological stress. Methods: A total of 20 healthy adults (ten female) and eight patients with central DI (four female) underwent the Trier Social Stress Test including, in order, 30-min waiting period, 10-min anticipation period, 10-min test period and 40-min recovery. Serum copeptin and cortisol concentrations and self-rated stress component feelings were determined in the pre-/postanticipation period, post-test period and twice post-recovery. Results: In healthy volunteers, the median (25th-75th percentile) copeptin concentration peaked immediately during the post-test period at 5.1 (3.2-7.0) pmol/l, vs 3.7 (2.6-5.4) pmol/l at baseline. Over the measurement course, copeptin concentration significantly elevated (coefficient; 95% CI) (0.14; 0.06-0.23, PZ0.002). The important predictors of increase in copeptin concentration were feelings of tension (0.06; 0.04-0.08, P!0.001) and avoidance (0.07; 0.04-0.10; P!0.001). Copeptin and cortisol levels were associated (0.43; 0.13-0.72, P!0.005). Patients with DI had lower baseline concentrations (1.55 (1.2-3.1) pmol/l) when compared with healthy volunteers, PZ0.006. Patients with DI showed no increase upon psychological stress (peak 2.15 pmol/l (1.5-2.28), PZ0.79). By contrast, cortisol values were similar in patients and volunteers. Conclusions: In healthy volunteers, copeptin levels significantly increased after psychological stress testing; this response was blunted in patients with DI.

Regardless of nutrient type ingested, copeptin did not increase, suggesting values can be interpreted independently of prandial status.

ObjectivesCytokines such as IL-1 seems to play a role in the pathogenesis of fatigue associated with some chronic diseases and anti-inflammatory treatment has been shown to reduce these symptoms.Ingestion of a calorie rich meal leads to postprandial fatigue, and is associated with increased systemic concentrations of cytokines, which is more pronounced in obese than lean subjects.We investigated whether postprandial fatigue is regulated by IL-1, and therefore reduced by IL-1 antagonism, in lean and obese subjects.MethodsIn a double-blind, crossover study in 8 lean and 8 obese male subjects, randomized to receive either saline (placebo) or the IL-1 receptor antagonist anakinra, we investigated whether postprandial fatigue was regulated by IL-1. To promote postprandial fatigue, subjects ran 30 min prior to a high-fat, high-carbohydrate meal. Fatigue was determined using the Stanford Sleepiness Scale and blood samples were drawn at baseline and after the intervention.ResultsIL-1 antagonism led to a reduction in postprandial fatigue and this effect was more pronounced in obese than lean individuals.ConclusionsWe conclude that IL-1 is involved in the regulation of postprandial fatigue under physiologic conditions in lean and obese individuals. It remains to be shown whether this effect translates into clinical relevant effects.

Context Thyroid hormone is crucial for the adaptation to cold. Objective To evaluate the effect of hyperthyroidism on resting energy expenditure (REE), cold-induced thermogenesis (CIT) and changes in body composition and weight. Design Prospective cohort study. Setting Endocrine outpatient clinic at tertiary referral center. Patients Eighteen patients with overt hyperthyroidism. Main Outcome Measures We measured REE during hyperthyroidism, after restoring euthyroid TH levels and after 3 months of normal thyroid function. In fourteen patients energy expenditure (EE) was measured before and after a mild cold exposure of two hours and CIT was the difference between EEcold and EEwarm. Skin temperatures at eight positions were recorded during the study visits. Body composition was assessed by dual X-ray absorption. Results Free T4 (fT4) and free T3 (fT3) decreased significantly over time (fT4, p=0.0003; fT3, p=0.0001). REE corrected for lean body mass (LBM) decreased from 42 ± 6.7 kcal/24h/kg LBM in the hyperthyroid to 33±4.4 kcal/24h/kg LBM (-21%, p<0.0001 vs hyperthyroid) in the euthyroid state and three months later to 33 ± 5.2 kcal/24h/kg LBM (-21%, p=0.0022 vs. hyperthyroid, overall p<0.0001). Free T4 (p=0.0001) and free T3 (p<0.0001) were predictors of REE. CIT did not change from the hyperthyroid to the euthyroid state (p=0.96). Hyperthyroidism led to increased skin temperature at warm ambient conditions but did not alter core body temperature, nor skin temperature after cold exposure. Weight regain and body composition were not influenced by REE and CIT during the hyperthyroid state. Conclusions CIT is not increased in patients with overt hyperthyroidism.