Frailty and the endocrine system

Frailty is a condition characterised by loss of biological reserves, failure of homoeostatic mechanisms, and vulnerability to adverse outcomes. The endocrine system is considered particularly important in frailty, because of its complex inter-relationships with the brain, immune system, and skeletal muscle. This Review summarises evidence indicating a key role for the hypothalamic–pituitary axis in the pathogenesis of frailty through aberrant regulation of glucocorticoid secretion, insulin-like growth factor signalling, and androgen production. Evidence also indicates a potential role for vitamin D and insulin resistance in the pathogenesis of frailty. The role of thyroid hormones in the pathogenesis of frailty remains uncertain. Key convergent pathological effects of frailty include loss of muscle mass and strength, with consequent impact on mobility and activities of daily living. Future translational research should focus on the understanding of endocrine mechanisms, to identify potential biomarkers of the condition, modifiable targets for treatment, and novel pharmacological drugs targeted at the endocrine components of frailty.