Effects of gender and age on hypothalamic–pituitary–adrenal reactivity after pharmacological challenge with low-dose 1-μg ACTH test: a prospective study in healthy adults


Correspondence: Michael Koutsilieris, Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias St. Goudi., Athens 11527, Greece. Tel.: +302107462507; Fax: +302107462571; E-mail: mkoutsil@med.uoa.gr



Τhe aim of this study was to observe cortisol responses to a pharmacological challenge with 1 μg ACTH as a function of age and gender.


Twenty-one young (13 women and 8 men; mean age: 43∙48 ± 10∙52 years) and forty elderly (20 women and 20 men; mean age: 79 ± 6∙76 years) volunteers without overt acute or chronic disease participated in this study.


Basal serum cortisol levels were measured, and cortisol values were obtained at 30 and 60 min after administration of 1 μg ACTH. Free thyroxine, triiodothyronine, thyrotrophin, prolactin, dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor-1, follicle stimulating hormone, luteinizing hormone, oestradiol levels in women and total testosterone levels in men were also measured at baseline.


No differences were observed between the groups of older and younger individuals in baseline plasma cortisol levels and mean cortisol responses at 30 and 60 min postchallenge. In the elderly subjects, statistically lower cortisol responses were observed in men at 30 and 60 min after 1-μg ACTH challenge (540∙17 ± 112∙28 vs 670∙11 ± 146∙49 nmol/l in women, = 0∙003 at 30 min, and 482∙24 ± 108∙14 vs 568∙04 ± 135∙73 nmol/l in women, = 0∙03 at 60 min).

Furthermore, significant lower values in PRL, IGF-1, DHEAS and T3 were detected in older subjects when compared to the younger age group.

Interestingly, a higher incidence of individuals who did not achieve normal responses to 1-μg ACTH test (>497 nmol/l) was noted in the group of elderly male subjects.


This study documents a marked gender effect in the elderly, in the cortisol response levels to 1-μg ACTH stimulation. Elderly men demonstrate a decreased responsiveness compared to women in the same age range.