Stress hormones, namely glucocorticoids, have diverse actions throughout the body in regulating development, tissue metabolism, inflammation, circadian rhythms, and skeletal homeostasis. While endogenous glucocorticoid levels are important to support bodily homeostasis, chronically elevated levels can cause damage to tissues and drive diseases including bone loss (i.e., osteoporosis), myopathy (i.e., sarcopenia) and metabolic disturbances (i.e., glucose intolerance, diabetes, and abnormal fat accrual). There is substantial evidence that basal glucocorticoid levels increase during ageing while at the same time the amplitude of the diurnal variation in glucocorticoid secretion decreases. However, the significance of these changes for skeletal health is not well understood and has only recently been studied in more detail. Evidence from genetically modified mouse models indicates that changes in glucocorticoid signaling associated with ageing induce bone loss, sarcopenia and drive osteoarthritic joint disease. These studies provide important insights into the role of glucocorticoids in age-related skeletal diseases which will aid in the development of novel treatments especially needed for osteoarthritis which disproportionally affects the elderly.

The escalating prevalence of diabetes poses a significant health concern. Uncontrolled diabetes leads to a multitude of complications. A comprehensive management plan and continual adaptation of guidelines is needed. The American Diabetes Association (ADA) is a guiding force in this domain, providing diabetes care recommendations for clinicians, laboratorians, researchers, and policymakers since 1989. The latest ADA guidelines present both challenges and opportunities for laboratories. The increased emphasis on glycated hemoglobin (HbA1c) testing for early diagnosis and personalized monitoring is expected to increase testing volumes, potentially leading to a rise in point-of-care testing. Ensuring standardized testing procedures becomes paramount to maintaining consistent and reliable results across laboratories. Moreover, laboratories may need to expand their test menus to accommodate the growing demand for personalized medicine approaches and collaborate closely with healthcare providers to support informed decision-making. This commentary provides a focused analysis of the 2024 ADA guidelines for the laboratory assessment of diabetes.

Stress is a state of threatened or perceived as threatened homeostasis that can be induced by various external and internal stimuli such as psychosocial factors, inflammatory or injurious conditions, and infections. In order to restore body homeostasis, adrenal glands produce and secrete glucocorticoids (GCs) and catecholamines (CAs), which are the main stress hormones that support the survival and adaptation of the organisms to the new environment. In contrast to the rather beneficial impact of acute and short-lasting stress, chronic stress and related dysregulation of the stress system is implicated in the development of many non-communicable diseases, including cancer. Particularly, ever-increasing experimental and clinical evidence implicates the involvement of CAs and GCs as well as the overexpression of their receptors in the activation of the major pathways involved in tumour development, metastasis, and resistance to various therapies. More importantly, results of experimental and epidemiological studies revealed that overexposure to stress hormones during pre- and early postnatal life might induce life-long or even transgenerational dysregulation of the stress system and predispose it to the development of various tumours. Although the exact mechanisms involved in the latter process are not yet fully known, it has been demonstrated that GC-induced epigenetic modifications can change the expression of several key genes involved in the regulation of the stress system, tumour initiation, and epigenetic imprinting. When such alterations occur in stem/progenitor cells (SPCs), this might not only lead to long-term dysfunction of the stress system but might promote the generation of cancer stem cells (CSCs). This review article discusses a hypothesis that stress hormones-mediated epigenetic reprograming of various SPCs during sensitive developmental periods, might contribute to their dysfunction and increased sensitivity to malignant transformation, thereby promoting tumorigenesis.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency leads to high morbidity and mortality, despite the availability of life-saving corticosteroid replacement therapy. Gene therapy represents a promising potential treatment for monogenic disorders such as congenital adrenal hyperplasia, overcoming the limitations of corticosteroid replacement approaches. Adeno-associated viral vectors are currently the leading vector for direct in vivo gene delivery. However, physiological properties of the adrenal gland limit the application of adeno-associated viral vector-based gene addition strategies. To achieve durable correction in the adrenal gland, gene editing must be employed to stably introduce a genetic modification into the CYP21A2 locus. The safety of this and other gene editing approaches could be greatly improved by using lipid nanoparticles for the delivery of editing machinery mRNA. While little data exists regarding adrenocortical lipid nanoparticle targeting, physiological features of this organ (such as high relative blood flow, fenestrated endothelium, and cholesterol uptake) indicate the promise of these delivery vectors for the treatment of monogenic diseases of the adrenal cortex. This review discusses the complexities of developing gene therapy for congenital adrenal hyperplasia and explores the viability of novel gene therapy strategies in this application.