Seasonal hormone oscillations in humans governed by gland-size-control feedback loops

Many clinical phenomena show hormone deregulation that lasts for months. Examples include long recovery times after steroid-withdrawal and after removal of hormone-secreting tumors. However, the origin of the months-timescale is unknown, given that hormones have lifetimes of hours and gene-expression changes take days. Here we propose that this timescale originates from the turnover-times of hormone glands. We use theory and large-scale electronic medical-records to establish a feedback-loop in the cortisol axis, in which the adrenal and pituitary control each other’s size with a response-time of months. This feedback enables both glands to set their functional mass and buffer physiological changes. It predicts seasonal hormone oscillations in agreement with blood-test datasets and gland-volume measurements: cortisol, thyroxin and sex hormones peak in winter-spring; LH/FSH and TSH in summer. The circuit also explains hormone dysregulation after steroid-withdrawal. Thus, networks of interacting organs can show seasonality and changes over months that affect physiology.