Background: Gradual ascent to high altitude is typically associated with reduced resting aldosterone and unchanged cortisol, features that may facilitate acclimatization but are poorly understood. Aims: To investigate the cortisol and aldosterone response to adrenocorticotrophic hormone at altitude. Methods: Eleven subjects underwent a 250 µg short synacthen test at sea-level and again after trekking to 3600 m in Nepal. Cortisol and aldosterone were measured by conventional assay from blood samples taken immediately prior to the administration of synacthen (T0) and then 30 (T30) and 60 (T60) minutes later. Results: At 3600 m resting basal cortisol and aldosterone levels were both significantly lower than they were at sea-level (p=0.004, p=0.003 respectively). Cortisol values at T30 and T60 were no different between sea-level and 3600 m but the increment after synacthen was significantly (p=0.041) greater at 3600 m due to a lower basal value. Aldosterone at T30 and T60 was significantly lower (p=0.003 for both) at 3600 m than at sea-level and the increment following synacthen was also significantly (p=0.003) less at 3600 m. Conclusions: At 3600 m there appears to be a divergent adrenal response to synthetic adrenocorticotrophic hormone with an intact cortisol response but a reduced aldosterone response, relative to sea-level. This may reflect a specific effect of hypoxia on aldosterone synthesis and may be beneficial to acclimatization
