Disrupted cortisol–ACTH relationships in elderly women given corticotrophin-releasing hormone two weeks after proximal femur fracture

Abstract

In elderly women with hip fractures plasma cortisol is persistently higher than in healthy elderly women, possibly causing undesirable catabolic effects. A lack of corresponding changes in plasma ACTH or in the cortisol response to exogenous ACTH has prompted us to study cortisol-ACTH relationships after giving corticotrophin-releasing hormone (CRH) to such subjects. Seventeen women aged 70-90 years who had sustained a hip fracture about two weeks previously were compared with 19 healthy women aged 68-85 years. 100 microg CRH was injected into each subject and ACTH and cortisol concentrations were measured at intervals for 90 minutes beforehand and 180 minutes afterwards. The concentrations of vasopressin and various cytokines and related peptides were also measured during the baseline period. Under baseline conditions plasma cortisol was higher and plasma ACTH lower in the injured patients than in the healthy subjects. The patients showed smaller incremental ACTH and cortisol responses to CRF but because of the higher baseline value the peak cortisol concentration was enhanced. A strong correlation between the cortisol and ACTH responses in the healthy subjects was completely lost in the patients and the slope of the ACTH-cortisol dose-response relationship varied greatly between individuals, with no overall increase. The concentrations of vasopressin, interleukin-1 receptor antagonist and soluble tumour necrosis factor receptors were higher in the patients but did not correlate with the responses to CRH. The results are not consistent with increased sensitivity to ACTH and suggest an independent stimulus to the adrenals of hip-fracture patients. Its identity is unknown as the non-ACTH stimuli proposed hitherto are reported to enhance sensitivity to ACTH.