Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of the disease. Because adrenal hormones are secreted with both circadian and ultradian periods, conventional single-time point measurements provide limited information about rhythmicity and, crucially, do not provide information during sleep, when many hormones fluctuate from nadir to peak concentrations. If blood sampling is attempted overnight, then this necessitates admission to a clinical research unit, can be stressful, and disturbs sleep. To overcome this problem and to measure free hormones within their target tissues, we used microdialysis, an ambulatory fraction collector, and liquid chromatography-tandem mass spectrometry to obtain high-resolution profiles of tissue adrenal steroids over 24 hours in 214 healthy volunteers. For validation, we compared tissue against plasma measurements in a further seven healthy volunteers. Sample collection from subcutaneous tissue was safe, well tolerated, and allowed most normal activities to continue. In addition to cortisol, we identified daily and ultradian variation in free cortisone, corticosterone, 18-hydroxycortisol, aldosterone, tetrahydrocortisol and allo-tetrahydrocortisol, and the presence of dehydroepiandrosterone sulfate. We used mathematical and computational methods to quantify the interindividual variability of hormones at different times of the day and develop "dynamic markers" of normality in healthy individuals stratified by sex, age, and body mass index. Our results provide insight into the dynamics of adrenal steroids in tissue in real-world settings and may serve as a normative reference for biomarkers of endocrine disorders (ULTRADIAN, NCT02934399).
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http://dx.doi.org/10.1126/scitranslmed.adg8464 | DOI Listing |
J Med Case Rep
January 2025
Cardiovascular Surgery Department, Shahid Rajaee Hospital, Alborz University of Medical Sciences, Karaj, Iran.
Background: The coexistence of pheochromocytoma and hyperaldosteronism is a rare and clinically significant finding with diagnostic challenges that need to be considered in the workup of patients with hypertension.
Case Presentation: This case report describes a 47-year-old Iranian man who initially presented with cold symptoms, chills, and headaches. Despite being diagnosed with panic disorder, his symptoms worsened, leading to a systolic blood pressure crisis.
PLoS One
January 2025
Department of Pain Medicine, Aichi Medical University, Nagakute, Aichi, Japan.
Background: Lowering barometric pressure (LP) can exacerbate neuropathic pain. However, animal studies in this field are limited to a few conditions. Furthermore, although sympathetic involvement has been reported as a possible mechanism, whether the sympathetic nervous system is involved in the hypothalamic-pituitary-adrenal (HPA) axis remains unknown.
View Article and Find Full Text PDFStress
December 2025
Department of Preclinical Fluid Biomarkers & Occupancy, H. Lundbeck A/S, Valby, Denmark.
Chronic stress and stress-related mental illnesses such as major depressive disorder (MDD) constitute some of the leading causes of disability worldwide with a higher prevalence in women compared to men. However, preclinical research into stress and MDD is heavily biased toward using male animals only. Aberrant activity of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to the development of MDD and several animal models of MDD have been established based on HPA axis dysregulation.
View Article and Find Full Text PDFJ Am Acad Orthop Surg Glob Res Rev
January 2025
From the Steadman Hawkins Clinic of the Carolinas, Prisma Health-Upstate, Greenville, SC (Dr. Pill, Dr. Ahearn, Dr. Siffri, Dr. Burnikel, Dr. Cassas, Dr. Wyland, and Dr. Kissenberth); the Mayo Clinic Arizona, Scottsdale, AZ (Dr. Tokish); the Department of Orthopaedics, Duke University, Durham NC (Dr. Cook); the Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson University, Clemson, SC (Dr. Mercuri, Mr. Sawvell, and Mr. Wright); the Frank H. Stelling and C. Dayton Riddle Orthopaedic Education and Research Laboratory, Clemson University Biomedical Engineering Innovation Campus, Greenville, SC (Dr. Mercuri, Mr. Sawvell, and Mr. Wright); and the Hawkins Foundation, Greenville, SC (Dr. Hutchinson, Dr. Bynarowicz, and Dr. Adams).
Introduction: The use of corticosteroid injections for short-term pain relief for knee osteoarthritis can have deleterious adverse effects. Amniotic tissue has shown promise in vitro; therefore, this study compared a morcellized injectable amniotic tissue allograft to corticosteroid injection.
Methods: Eighty-one patients with symptomatic severe knee osteoarthritis (Kellgren-Lawrence grade 3 to 4) were prospectively randomized to either a double-blinded single injection of BioDRestore (Integra LifeSciences; n = 39) or triamcinolone acetonide (n = 42).
Hum Genomics
January 2025
Department of Endocrine and Metabolic Diseases, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
Background: The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P.
Methodology: This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH.
Results: A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands).
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