Tissue Glucocorticoid Metabolism in Adrenal Insufficiency:A Prospective Study of Dual-release Hydrocortisone Therapy

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.Study Design and Methods: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.Results: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.Conclusion: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC

Strength and conditioning coaches\u27 application of the session rating perceived exertion method of monitoring within professional rugby union

Session rating of perceived exertion (session-RPE) is a method of monitoring and managing training loads. The purpose of this study was to research how and for what purpose strength and conditioning (S&C) coaches implement this monitoring method within professional rugby union. The study also aimed to assess if S&C coaches found this monitoring method to be valid and effective. An online survey containing 24 fixed response questions was used to assess how S&C coaches applied the session-RPE method. The survey was piloted with expert researchers and practitioners in the area of session-RPE prior to distribution and alterations were made to the survey based on the experts’ feedback. Twenty S&C coaches working with professional rugby union clubs in Ireland, England, Scotland and Wales completed the survey. The coaches’ responses indicated that the majority found the session-RPE to be a valid and effective monitoring method. While some good implementation practices were identified, not all of the coaches adhered to these guidelines which may impact on the accuracy of the collected data. For example, 30% of coaches do not collect the RPE for every session that a player does per week limiting the use of the session-RPE variables cumulative training load, training monotony, training strain and acute:chronic load ratio. S&C coaches within rugby should consider using session-RPE as a method of monitoring and implement the method in a manner reflective of research findings to enhance the potential applications of this system in maximising adaptations and minimising the risk of injury

Strength and conditioning coaches' application of the session rating perceived exertion method of monitoring within professional rugby union

Session rating of perceived exertion (session-RPE) is a method of monitoring and managing training loads. The purpose of this study was to research how and for what purpose strength and conditioning (S&C) coaches implement this monitoring method within professional rugby union. The study also aimed to assess if S&C coaches found this monitoring method to be valid and effective. An online survey containing 24 fixed response questions was used to assess how S&C coaches applied the session-RPE method. The survey was piloted with expert researchers and practitioners in the area of session-RPE prior to distribution and alterations were made to the survey based on the experts’ feedback. Twenty S&C coaches working with professional rugby union clubs in Ireland, England, Scotland and Wales completed the survey. The coaches’ responses indicated that the majority found the session-RPE to be a valid and effective monitoring method. While some good implementation practices were identified, not all of the coaches adhered to these guidelines which may impact on the accuracy of the collected data. For example, 30% of coaches do not collect the RPE for every session that a player does per week limiting the use of the session-RPE variables cumulative training load, training monotony, training strain and acute:chronic load ratio. S&C coaches within rugby should consider using session-RPE as a method of monitoring and implement the method in a manner reflective of research findings to enhance the potential applications of this system in maximising adaptations and minimising the risk of injury