Susceptibility to Adrenal Crisis Is Associated With Differences in Cortisol Excretion in Patients With Secondary Adrenal Insufficiency

Objective: To compare cortisol pharmacokinetics and pharmacodynamics mapped through several glucocorticoid sensitive pathways in patients on hydrocortisone substitution with or without an adrenal crisis. Design: A post-hoc analysis of a previously conducted randomized controlled trial in patients with secondary adrenal insufficiency examining the effects of 2 weight-adjusted hydrocortisone doses. Methods: Comparisons were primarily made on a hydrocortisone dose of 0.2-0.3 mg/kg/day for plasma cortisol and cortisone, 24-hour urinary steroid profile, the glucocorticoid sensitive tryptophan-kynurenine pathway, the renin-angiotensin-aldosterone system and aspects of quality of life. Variables of interest were also analyzed on the hydrocortisone dose of 0.4-0.6 mg/kg/day. Results: Out of 52 patients, 9 (17%) experienced at least one adrenal crisis (AC+ group) and 43 did not develop an adrenal crisis (AC- group) during an observation period of 10 years. 24-hour urinary excretion of cortisol and cortisone were lower in the AC+ group (0.05 [IQR 0.03; 0.05] vs. 0.09 [0.05; 0.12] µmol/24h, P=0.01and 0.13 [0.10; 0.23] vs. 0.24 [0.19; 0.38] µmol/24h, P=0.04, respectively). No differences in pharmacokinetics of cortisol were observed. Kynurenine concentrations were higher in the AC+ group (2.64 [2.43; 3.28] vs. 2.23 [1.82; 2.38] µmol/L, P=0.03) as was general fatigue (Z-scores 1.02 [-0.11; 1.42] vs. -0.16 [- 0.80; 0.28], P=0.04). On the higher hydrocortisone dose urinary excretion of cortisol and cortisone was still significantly lower between the AC- and AC + group. The differences in glucocorticoid sensitive variables disappeared. Conclusion: Patients susceptible to an adrenal crisis demonstrated differences in cortisol and cortisone excretion as well as in pharmacodynamics when compared to patients who did not experience an adrenal crisis, suggesting a biological predisposition in certain patients for the development of an adrenal crisis

From thorium phosphate hydrogenphosphate hydrate to β\beta-thorium phosphate diphosphate: Structural evolution to a radwaste storage ceramic

$\beta$-Thorium phosphate diphosphate ($\beta$-TPD), considered as a very promising radwaste storage material, was obtained from thorium phosphate hydrogenphosphate hydrate (TPHPH) precursor through dehydration and hydrogen phosphate condensation. The structures of TPHPH, intermediate $\alpha$-thorium phosphate diphosphate ($\alpha$-TPD) and its hydrate ($\alpha$-TPDH) have been resolved ab initio by Rietveld analysis of their synchrotron diffraction patterns. All were found orthorhombic (space group Cmcm) and similarly composed of [ThPO$_4$]$_4^{4+}$ slabs alternating with disordered layers hosting either [HPO$_4$·H$_2$O]$_2^{4-}$ (TPHPH), [P$_2$O$_7$·2H$_2$O]$^{4-} ($\alpha$-TPDH), or [P$_2O_7$]$^{4-}$($\alpha$-TPD), unlike the 3D structure of$\beta$-TPD. The diphosphate groups of$\alpha$-TPD and$\alpha$-TPDH are strongly bent. The irreversible transition to the final$\beta$-TPD consists in a shearing of the slabs and a reduction of the interslabs cavities that explains the stability of this high-temperature form

Defect-unbinding and the Bose-glass transition in layered superconductors

The low-field Bose-glass transition temperature in heavy-ion irradiated Bi_2Sr_2CaCu_2O_8+d increases progressively with increasing density of irradiation-induced columnar defects, but saturates for densities in excess of 1.5 x10^9 cm^-2. The maximum Bose-glass temperature corresponds to that above which diffusion of two-dimensional pancake vortices between different vortex lines becomes possible, and above which the ``line-like'' character of vortices is lost. We develop a description of the Bose-glass line that is in excellent quantitative agreement with the experimental line obtained for widely different values of track density and material parameters.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Let