Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

Objectives: The treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing's syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids. Design: This was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH. Methods: Twenty-four-hour serum sampling for ACTH, 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, DHEA, testosterone, progesterone and 24-h urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration was calculated. Results: A significant rhythm was confirmed for ACTH (r2, 0.95; P<0.001), 17OHP (r2, 0.70; P=0.003), androstenedione (r2, 0.47; P=0.043), androsterone (r2, 0.80; P<0.001), testosterone (r2, 0.47; P=0.042) and progesterone (r2, 0.64; P=0.006). The mean (S.D.) TminAC and TmaxAC for 17OHP and A4 were: morning prednisone (4.3 (2.3) and 9.7 (3.5) h), evening prednisone (4.5 (2.0) and 10.3 (2.4) h), and daily dexamethasone (9.2 (3.5) and 16.4 (7.2) h). AUC0–24 h progesterone, androsterone and 24-h urine pdiol were significantly related to 17OHP. Conclusion: In CAH patients, adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers

The forward physics facility at the high-luminosity LHC

High energy collisions at the High-Luminosity Large Hadron Collider (LHC) produce a large number of particles along the beam collision axis, outside of the acceptance of existing LHC experiments. The proposed Forward Physics Facility (FPF), to be located several hundred meters from the ATLAS interaction point and shielded by concrete and rock, will host a suite of experiments to probe standard model (SM) processes and search for physics beyond the standard model (BSM). In this report, we review the status of the civil engineering plans and the experiments to explore the diverse physics signals that can be uniquely probed in the forward region. FPF experiments will be sensitive to a broad range of BSM physics through searches for new particle scattering or decay signatures and deviations from SM expectations in high statistics analyses with TeV neutrinos in this low-background environment. High statistics neutrino detection will also provide valuable data for fundamental topics in perturbative and non-perturbative QCD and in weak interactions. Experiments at the FPF will enable synergies between forward particle production at the LHC and astroparticle physics to be exploited. We report here on these physics topics, on infrastructure, detector, and simulation studies, and on future directions to realize the FPF's physics potential

Urinary iodine percentile ranges in the United States.

BACKGROUND: The status of iodine nutrition of a population can be determined by measurement of urinary iodine concentrations since it is thought to indicate dietary iodine intake. Normally, these results are compared to population-based criteria, since there are no reference ranges for urinary iodine. OBJECTIVE: To determine the percentile ranges for urinary iodide (UI) concentrations in normal individuals in the United States. MATERIALS AND METHODS: The third National Health and Nutrition Examination Survey (NHANES III) (1988–1994) database of the civilian, non-institutionalized, iodine-sufficient US population was used. The 2.5th to 97.5th percentile ranges for urinary iodine and for urinary iodine per gram creatinine ratio (UI/Cr) (μg/g) were calculated for females and males, 6–89 years of age, each stratified by age groups. RESULTS AND CONCLUSIONS: We calculated the percentile ranges for urinary iodine. After exclusions of subjects with goiter or thyroid disease, the study sample included 21,530 subjects; 10,439 males and 11,091 females. For women of childbearing age (14–44 years), urinary iodine concentration 2.5th to 97.5th percentiles are 1.8–65 μg/dl or 36–539 μg/g creatinine. For pregnant women, the ranges are 4.2–55 μg/dl or 33–535 μg/g creatinine