Twenty-Four Hour Cortisol Release Profiles in Patients With Alzheimer’s and Parkinson’s Disease Compared to Normal Controls: Ultradian Secretory Pulsatility and Diurnal Variation

Abstract

Endocrine abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD) have been described repeatedly. However, no data are available on the diurnal cortisol secretory pattern in these major neurodegenerative disorders. Therefore, we studied 24-h pulsatile cortisol secretion in 12 patients with AD and 12 patients with PD compared to 10 normal community- and age-matched volunteers (NV). Twenty-four hour blood sampling was performed from 1800 h to 1800 h at 15-min intervals. Cortisol half-life, number of cortisol secretory bursts/24-h, interpulse interval, mass of cortisol secreted per burst, amplitude of cortisol secretory bursts, pulsatile cortisol production rate, 24-h mean, and integral cortisol concentrations were calculated by applying deconvolution analysis. Furthermore, the relative diurnal variation and the quiescent period were determined. Patients with AD and PD were found to have significantly higher total plasma cortisol concentrations (24-h pulsatile cortisol production rate: AD + 56%; PD + 52%/24-h integrated cortisol: AD + 37%; PD + 29%) compared to NV. This sustained hypercortisolism is due to a higher mass of cortisol secreted per burst (AD + 62%; PD + 79%), but not to increased cortisol half-life or secretory pulse frequency or amplitude. Despite these similarities between AD and PD patients, relative diurnal variation of cortisol secretion was significantly decreased in patients with PD (−22%), whereas the pattern of secretory curves was not different between NV and AD patients. This observation was indirectly supported by a reduction of the quiescent period in patients with PD (−74 min) compared to the NV and AD group. Based on these results and recently published animal data, we hypothesize that decreased expression of hippocampal mineralocorticoid receptors (MR) may account for the flattened diurnal cortisol secretory curve observed in PD patients, whereas the intact diurnal profile in AD patients may be due to a relative increase in MR compensating for the hippocampal neuronal loss commonly occurring in this disorder.