SENSITIVITY OF MONONUCLEAR LEUKOCYTES TO GLUCOCORTICOIDS IN ELDERLY HIP-FRACTURE PATIENTS RESISTANT TO SUPPRESSION OF PLASMA-CORTISOL BY DEXAMETHASONE

Objective: Elderly women with proximal femur fracture show a prolonged increase in plasma cortisol, which could have undesirable catabolic e ffects. Suppression of cortisol by dexamethasone is impaired, suggesti ng resistance to glucocorticoid effects at feedback inhibitory sites. We therefore wished to find out whether peripheral glucocorticoid sens itivity is normal. Design: Peripheral blood mononuclear leucocytes wer e used as a model tissue. Blood samples were taken from elderly women about 2 weeks after hip fracture and from elderly control women. Each patient was then given 1 mg dexamethasone at 2300 h followed by furthe r sampling at 0800 and 1600 h the next day. Methods: Glucocorticoid-re ceptor binding parameters were measured by incubating whole cells with [H-3]dexamethasone for 2 h at 37 degrees C. Inhibition of cell prolif eration by dexamethasone was assessed by addition of [H-3]thymidine to cells cultured for 65 h with concanavalin A. Cortisol and dexamethaso ne concentrations were measured in the dexamethasone suppression test. Results: As expected, the hip-fracture patients had raised morning co rtisol concentrations and impaired suppression by dexamethasone. The c ells of the patients had similar numbers of glucocorticoid receptors t o those of the control subjects but higher values for K-d (i.e. a lowe r binding affinity). The cells of the patients incorporated less [H-3] thymidine than the control cells in the absence of dexamethasone. The percentage inhibition by a saturating concentration of dexamethasone w as unchanged but the concentration giving half-maximal inhibition was decreased (sensitivity was increased) at the higher of the two concana valin A concentrations used. Conclusions: These experiments in mononuc lear leucocytes give no evidence of peripheral resistance to glucocort icoids in hip-fracture patients with impaired suppression of cortisol by dexamethasone.