Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy DOI Open Access
Marianna Minnetti, Valeria Hasenmajer, Riccardo Pofi

et al.

Journal of Endocrinology, Journal Year: 2020, Volume and Issue: 246(2), P. R13 - R31

Published: May 7, 2020

The circadian rhythm derives from the integration of many signals that shape expression clock-related genes in a 24-h cycle. Biological tasks, including cell proliferation, differentiation, energy storage, and immune regulation, are preferentially confined to specific periods. A gating system, supervised by central peripheral clocks, coordinates endogenous exogenous prepares for transition activities periods light or darkness. fluctuations cortisol its receptor crucial modulating these signals. Glucocorticoids autonomous nervous system act as bridge between suprachiasmatic master clock almost all clocks. Additional synchronizing mechanisms metabolic fluxes cytokines stabilize network. pacemaker is amplified peaks troughs their response food, activity, inflammation. However, when glucocorticoid exposure pattern becomes chronically flattened at high- (as Cushing's syndrome) low adrenal insufficiency) levels, fails. While endocrinologists well aware rhythm, too little attention has been given interventions aimed restoring physiological disorders. acting on levels may not be only way restore activities. First, counterregulatory mechanism itself controls signal transduction, second, melatonin and/or metabolically active drugs nutrients could also used modulate clock. All aspects described herein, providing some insights into emerging role chronopharmacology, focusing excess deficiency

Language: Английский

The human stress response DOI
Georgina Russell, Stafford L. Lightman

Nature Reviews Endocrinology, Journal Year: 2019, Volume and Issue: 15(9), P. 525 - 534

Published: June 27, 2019

Language: Английский

Citations

687
Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management DOI Open Access
Hedi L. Claahsen‐van der Grinten, Phyllis Speiser, S. Faisal Ahmed

et al.

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(1), P. 91 - 159

Published: May 7, 2021

Abstract Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity an enzyme required for production leads to chronic overstimulation the cortex and accumulation precursors proximal blocked enzymatic step. The most common form CAH caused by steroid 21-hydroxylase deficiency due mutations in CYP21A2. Since last publication summarizing Endocrine Reviews 2000, there have been numerous new developments. These include more detailed understanding steroidogenic pathways, refinements neonatal screening, improved diagnostic measurements utilizing chromatography mass spectrometry coupled with profiling, genotyping methods. Clinical trials alternative medications modes delivery recently completed or are under way. Genetic cell-based treatments being explored. A large body data concerning long-term outcomes patients affected CAH, including psychosexual well-being, has enhanced establishment disease registries. This review provides reader current insights special attention these

Language: Английский

Citations

357
Adrenal insufficiency DOI
Eystein S. Husebye, Simon H. S. Pearce, Nils Krone

et al.

The Lancet, Journal Year: 2021, Volume and Issue: 397(10274), P. 613 - 629

Published: Jan. 20, 2021

Language: Английский

Citations

251
Adrenal insufficiency DOI
Stefanie Hahner, Richard Ross, Wiebke Arlt

et al.

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: March 11, 2021

Language: Английский

Citations

110
Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad? DOI Creative Commons
Riccardo Pofi, Giorgio Caratti, David Ray

et al.

Endocrine Reviews, Journal Year: 2023, Volume and Issue: 44(6), P. 975 - 1011

Published: May 30, 2023

Abstract It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action glucocorticoids deliver therapeutic benefit not in doubt. However, side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, a significant health economic burden. precise cellular mechanisms underpinning differential drive desirable undesirable still completely understood. Faced unmet clinical need limit glucocorticoid-induced adverse alongside ensuring preservation actions, several strategies have been pursued. coprescription existing licensed drugs treat incident can be effective, but data examining prevention limited. Novel selective receptor agonists modulators designed aim specifically selectively activate responses based upon interaction receptor. Several these compounds trials evaluate efficacy. More recently, exploiting tissue-specific metabolism through isoforms 11β-hydroxysteroid dehydrogenase has shown early potential, although from any treatment maximize while minimizing risk, within this review we define effect profile use current developing preserve

Language: Английский

Citations

69
COVID-19 infection and glucocorticoids: update from the Italian Society of Endocrinology Expert Opinion on steroid replacement in adrenal insufficiency DOI Creative Commons
Andrea M. Isidori, Giorgio Arnaldi, Marco Boscaro

et al.

Journal of Endocrinological Investigation, Journal Year: 2020, Volume and Issue: 43(8), P. 1141 - 1147

Published: April 25, 2020

SARS Severe acute respiratory syndrome GC Glucocorticoid CIRCI Critical illness relative corticosteroid insufficiency AI Adrenal In November 2019, the Italian Society of Endocrinology (SIE) has published a consensus statement on tailoring glucocorticoid replacement in adrenal [1].A few months later, novel severe coronavirus (SARS-CoV2) been recognized as responsible for COVID-19.The outbreak now reached pandemic level, with high global mortality rate [2].From February on, Italy experienced an exponential rise infected which is estimated to reach 200,000 people, overall lethality approximately 10% [3].A recent Chinese series nearly 50,000 patients confirmed COVID-19 infection found that one-out-of-five (19%) evolve towards (14%) or critical (5%) pneumonia [4].Several clinical trials are testing therapeutic options treat lung and extra-respiratory complications SARS-CoV2 infection.While awaiting specific treatment strategy, SIE task force met again address insufficient coping stress related infection.

Language: Английский

Citations

119
The Immune System in Cushing’s Syndrome DOI
Valeria Hasenmajer, Emilia Sbardella, Francesca Sciarra

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2020, Volume and Issue: 31(9), P. 655 - 669

Published: May 6, 2020

Language: Английский

Citations

111
Epidemiology, pathogenesis, and diagnosis of Addison’s disease in adults DOI
Corrado Betterle, Fabio Presotto, Jadwiga Furmaniak

et al.

Journal of Endocrinological Investigation, Journal Year: 2019, Volume and Issue: 42(12), P. 1407 - 1433

Published: July 18, 2019

Language: Английский

Citations

108
Chronopharmacology of glucocorticoids DOI

Megerle L. Scherholz,

Naomi Schlesinger, Ioannis P. Androulakis

et al.

Advanced Drug Delivery Reviews, Journal Year: 2019, Volume and Issue: 151-152, P. 245 - 261

Published: Feb. 22, 2019

Language: Английский

Citations

107
Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility DOI Open Access
Francesca Sciarra, Edoardo Franceschini, Federica Campolo

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(11), P. 3943 - 3943

Published: May 30, 2020

: Infertility represents a growing health problem in industrialized countries. Thus, greater understanding of the molecular networks involved this disease could be critical for development new therapies. A recent finding revealed that circadian rhythmicity disruption is one main causes poor reproductive outcome. The clock system beats rhythms and modulates several physiological functions such as sleep-wake cycle, body temperature, heart rate, hormones secretion, all which enable to function response 24 h cycle. This intricated machinery driven by specific genes, called "clock genes" fine-tune homeostasis. Stress modern lifestyle can determine changes hormone favoring onset infertility-related conditions might reflect disfunctions within hypothalamic-pituitary-gonadal axis. Consequently, loss suprachiasmatic nuclei affect pulsatile sexual release. Herein, we provide an overview findings, both animal models humans, about how fertility influenced rhythm. In addition, explore complex interaction among hormones, clock. deeper analysis these interactions lead novel insights ameliorate therapeutic management infertility related disorders.

Language: Английский

Citations

92