Cortisol, DHEAS and aging: resistance to cortisol suppression in frail institutionalized elderly

Convincing evidences has linked the hypothalamus-pituitary-adrenal (HPA) axis to aging patterns. F excess is implicated in the development of frailty characteristics whereas DHEAS is positively correlated to successful aging. We compared serum F and DHEAS levels of independent community-living (successful group, 19 M and 28 F, 69 to 87 yr) with those of institutionalized elderly (frail group, 20 M and 30 F, 65 to 95 yr). Serum F was determined at 1) baseline (08:00 h, 16:00 h and 23:00 h), 2) after 2 overnight dexamethasone (DEX) suppression tests (DST, using 0.25 and 1.0 mg doses), and 3) 60 min after ACTH stimulation (250 microg i.v. bolus); serum DHEAS was determined at 08:00 h. Basal serum F at 08:00 h, 16:00 h and 23:00 h and serum DHEAS levels were similar in both groups; however F: DHEAS ratio at 08:00 h was higher in the frail, compared to the successful group (mean +/- SD: 0.55 +/- 0.53 and 0.35 +/- 0.41, respectively; p = 0.04). In response to DST, F suppression was less effective in frail elderly after either 0.25 or 1.0 mg doses (9.0 +/- 6.0 and 2.0 +/- 0.9 microg/dl), as compared to the successful group (5.8 +/- 4.4 and 1.5 +/- 0.5 microg/dl) (p = 0.01). In addition, a significant correlation was observed between post-DEX F levels (both doses) and parameters of cognitive and physical frailty. Normal and similar F levels were observed after ACTH stimulation in both groups. Our data suggest a deficient feedback regulation of the HPA axis in frail institutionalized elderly, as demonstrated by a higher set point for F suppression. This augmented HPA tonus enforces the hypothesis that even milder F excess may be related to characteristics of frailty in the elderly.