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Interperson Variability but Intraperson Stability of Baseline Plasma Cortisol Concentrations, and Its Relation to Feedback Sensitivity of the Hypothalamo-Pituitary-Adrenal Axis to a Low Dose of Dexamethasone in Elderly Individuals¹

Departments of Internal Medicine III (N.A.T.M.H., J.W.K., P.deL., H.A.P.P., F.H.deJ., S.W.J.L.), Erasmus University Rotterdam and Dijkzigt University Hospital, 3015 GD Rotterdam; and Julius Center for Patient Orientated Research (R.P.S., D.E.G.), Utrecht University Medical School, 3508TA Utrecht, The Netherlands

Address all correspondence and requests for reprints to: Nannette A. T. M. Huizenga, Department of Internal Medicine III, Dijkzigt University Hospital, Room Bd 277-a Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.

In the present study, we investigated whether the negative feedback action of glucocorticoids (GCs) on the hypothalamo-pituitary-adrenal (HPA) axis changes with age. We performed a 1-mg dexamethasone (DEX) suppression test in 216 healthy elderly individuals. To investigate individual variability of feedback sensitivity in more detail, 2.5 yr later a 0.25-mg DEX suppression test was carried out in 164 of the same individuals. We investigated whether there was an effect of age or gender on both basal and post-DEX cortisol levels, as well as on the concentration of DEX. Furthermore, we examined whether the reactions to the two doses of DEX differed, and whether indications for an intraperson stability of baseline cortisol levels could be found.

Neither the pre- nor the post-1-mg DEX plasma cortisol concentrations showed a correlation with age, and there were no differences between men and women. The same was true for the pre- and post-0.25-mg DEX cortisol concentrations. In reaction to 1 mg DEX, over 90% of the subjects investigated showed a cortisol suppression to levels below 50 nmol/L. After the administration of 0.25 mg DEX, there was a much wider range in post-DEX cortisol concentrations. After the administration of 1 mg DEX, there was a significant correlation between liver function parameters and plasma DEX concentrations in males, and there was a correlation between body mass index and plasma DEX concentration in females. Plasma DEX concentrations after the administration of 1 mg and 0.25 mg DEX were closely correlated within subjects (P < 0.001).

There was an intraindividual stability of serum cortisol levels determined at an interval of 2.5 yr. Furthermore, the individuals with the highest baseline cortisol concentrations also had the highest post– 0.25-mg DEX cortisol concentrations, indicating a close relationship between basal cortisol levels and the feedback sensitivity of the HPA axis to a low dose of DEX. These observations suggest a genetic influence on the set point of the HPA axis. Aging does not seem to lead to a change in HPA activity as measured by early morning total cortisol levels. Also, no changes in the sensitivity of the feedback system to DEX were observed with age. DEX metabolism is influenced by liver function (in males) and by body mass index (in females).

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