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

Pediatric reference ranges for zinc protoporphyrin.

OBJECTIVES: To determine pediatric reference ranges for zinc protoporphyrin (ZPP). DESIGN AND METHODS: The study was conducted in a large pediatric hospital on patient blood specimens (n = 6,478) (0 – 17 y) accrued from January 2001 to June 2002. The data was analyzed employing the Hoffman approach, which was computer adapted. RESULTS AND CONCLUSIONS: The 2.5(th) and 97.5(th) percentiles for children age 0 to 12 months were 9 to 40 μg/dL (16.6 –73.6 μmol/mol heme) for female subjects and 8.5 to 34.5 μg/dL (15.6 – 63.5 μmol/mol heme) for males. The 97.5(th) percentiles decreased for the 13 to 24 months age group for females (32 μg/dL) (58.9 μmol/mol heme). There was a significant decrease in the 97.5(th) percentile for zinc protoporphyrin (ZPP) concentrations for the 5 to 9 yr age group, the 97.5(th) percentile being 30 μg/dL (55.2 μmol/mol heme) in both genders, which increased to 33.5 μg/dL (61.6 μmol/mol heme) in the 10 to 17 yr female age group but not for the males (31.5 μg/dL) (58.0 μmol/mol heme). The highest medians were 25.5 μg/dL (46.9 μmol/mol heme) for females, and 21.5 μg/dL (39.6 μmol/mol heme) for males in the 0 to 12 months age group