Gender‐specific co‐activation of arginine vasopressin and the hypothalamic–pituitary–adrenal axis during stress

OBJECTIVE: To study the interaction between copeptin and hypothalamic-pituitary-adrenal (HPA) activation in men and women during hypoglycaemic stress. DESIGN AND PATIENTS: A prospective study in 118 patients (mean age 47·7 ± 13·6 years, n = 52 women) undergoing insulin tolerance testing for suspected pituitary dysfunction. MEASUREMENTS: Serum copeptin was measured in serially collected blood samples and assessed in relation to ACTH, cortisol and other endocrine parameters. RESULTS: Symptomatic hypoglycaemia (mean glucose nadir, 1·6 ± 0·5 mmol/l) resulted in a rapid significant increase of serum copeptin. Individuals with impaired pituitary function had lower stress-induced copeptin levels (median, 6·26 pmol/l) than patients with intact pituitary (8·46 pmol/l, P < 0·001). A weak overall correlation between stress-induced copeptin and cortisol levels was observed (rs = 0·31, P < 0·001). In female individuals, there was a positive correlation between stress-induced copeptin and ACTH (rs = 0·47, P < 0·001) or cortisol levels (rs = 0·42, P = 0·002), while in males, no correlation with ACTH levels (rs = 0·03, P = 0·75) and poor correlation with cortisol levels (rs = 0·24, P = 0·045) was observed. Patients with central diabetes insipidus showed lowest baseline (2·20 pmol/l) and stimulated copeptin levels (3·68 pmol/l). CONCLUSIONS: The data from this study indicate that stress-induced release of AVP in women, but not in men, is linked to the co-activation of the hypothalamic-pituitary-adrenal system.