Elsevier

Neurobiology of Aging

Volume 18, Issue 3, May–June 1997, Pages 285-289
Neurobiology of Aging

Original Articles
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

https://doi.org/10.1016/S0197-4580(97)80309-0Get rights and content

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.

Section snippets

Protocol

Twenty-four hour pulsatile cortisol secretion was evaluated quantitatively in a) 12 patients with AD (4 male, 8 female patients; mean age: 63 ± 8.4 years; mean duration of illness: 4.3 ± 2.1 years), b) 12 patients with PD (10 male, 2 female patients; mean age: 61 ± 8.1 years; mean duration of illness: 12 ± 6.5 years), and 10 physically and mentally healthy controls (NV = normal volunteers; 7 male, 3 female; mean age: 68 ± 8.4 years). Severity of a possible concurrent depression in patients was

Results

Results are summarized in Table 1. Cortisol half-life, number of secretory bursts in 24 h, and the mean intersecretory pulse interval were almost identical among the three groups. Mass of cortisol secreted per burst was almost double in patients with AD compared to NV. However, this finding failed to reach statistical significance (p < 0.1), whereas in PD patients this mass was significantly greater than in NV. These differences were not related to amplitude of cortisol secretory bursts, which

Discussion

The results of the present study can be summarized as follows: patients with AD and PD secret significantly more cortisol in 24 h than NV. This difference is related to an elevated pulsatile cortisol production rate in both disease groups. Patients with AD and PD have higher masses of cortisol secreted per burst, but similar cortisol half-lives, secretory pulse frequencies or amplitudes as NV. Contrasting these similarities between AD and PD patients compared to NV, the relative diurnal

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