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Elderly subjects show severe impairment of dehydroepiandrosterone sulphate and reduced sensitivity of cortisol and aldosterone response to the stimulatory effect of ACTH1−24
Article first published online: 20 DEC 2001
DOI: 10.1046/j.1365-2265.2001.01317.x
1365-2265/asset/cover.gif?v=1&s=12f46dcf32f4f74f88c9417c07f542e55ab3fb5c "Clinical Endocrinology")
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Giordano, R., Di Vito, L., Lanfranco, F., Broglio, F., Benso, A., Gianotti, L., Grottoli, S., Ghigo, E. and Arvat, E. (2001), Elderly subjects show severe impairment of dehydroepiandrosterone sulphate and reduced sensitivity of cortisol and aldosterone response to the stimulatory effect of ACTH1−24. Clinical Endocrinology, 55: 259–265. doi: 10.1046/j.1365-2265.2001.01317.x
Publication History
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- (Received 9 November 2000; returned for revision 12 December 2000; finally revised 23 January 2001; accepted 16 March 2001)
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OBJECTIVE Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in ageing has been reported both in humans and in animals and may be involved in age-related changes in body composition, structure functions and metabolism, as well as in brain ageing. Despite the supposed HPA hyperactivity and its refractoriness to negative glucocorticoid feedback, low levels of dehydroepiandrosterone (DHEA) and its sulphate have been clearly demonstrated in human ageing and may suggest another cause of age-related changes in structure function and metabolism. Thus, our aim was to verify the adrenal responsiveness to various ACTH doses in normal elderly subjects.
DESIGN We studied cortisol (F), aldosterone (A) and DHEA responses to the sequential administration of very low, low and supramaximal ACTH1−24 doses (0·06 µg or 0·5 µg followed by 250 µg ACTH1−24 i.v. at 0 and +60 minutes) in healthy elderly subjects (ES) [six females and two males, aged 63–75 years, body mass index (BMI) 22–26 kg/m2]. The results in ES were compared with those recorded in healthy young subjects (YS) (six females and six males, aged 22–34 years, BMI 20–25 kg/m2).
RESULTS Basal DHEA levels in ES were lower (P < 0·05) than in YS, while F and A levels were similar in both groups. DHEA, F and A responses to ACTH were dose-dependent in both groups. In ES, however, DHEA levels showed no response to the 0·06 µg dose, a modest increase after 0·5 µg and a clearer rise after 250 µg ACTH; at any dose, the DHEA response in ES was clearly lower than in YS (P < 0·04). The F responses to 0·5 µg and 250 µg ACTH in ES were similar to those in YS; whereas, in ES, 0·06 µg ACTH elicited a non significant F increase which was significantly lower than in YS (P < 0·05). Similarly, the A responses to the highest ACTH doses were similar in both groups but, in ES, 0·06 µg ACTH elicited no increase in A secretion, which was clearly lower than in YS (P < 0·03).
CONCLUSIONS Normal elderly subjects show severe reduction of DHEA response to a wide range of ACTH doses, in agreement with peculiar impairment of the activity of the adrenal reticularis zone in ageing. In contrast to young adults, elderly subjects also show no cortisol and aldosterone response to a very low ACTH dose. This evidence indicates a reduced sensitivity to ACTH in the fasciculata and glomerulosa zones of the adrenal gland in ageing.