Dexamethasone effects on cortisol secretion in Alzheimer's disease: Some clinical and hormonal features in suppressor and nonsuppressor patients

Alterations in the hypothalamic-pituitary-adrenal axis (HPAA) and failure o f dexamethasone (DXT) to suppress cortisol secretion occur in Alzheimer's d isease (AD). This study was aimed to settle possible differences in some cl inical (age, body weight, body mass index, dementia severity) and hormonal parameters in AD patients non-responders to overnight 1 mg-DXT suppression test compared with the responder subjects. ACTH, cortisol and dehydroepiand rosterone sulphate (DHEAS) day-time levels were assessed in 25 AD patients and in 12 age-matched healthy controls before DXT administration. In view o f their neuroprotective effects, plasma levels of Insulin-like Growth Facto r-I (IGF-I) and of IGF-Binding Proteins (IGFBPs) were also determined. Afte r DXT, 8 AD subjects (32%) showed cortisol levels above the conventional cu t-off of 140 nmol/L. No significant differences were found in clinical para meters in suppressor vs nonsuppressor patients. AD subjects showed higher c ortisol, cortisol/DHEAS ratios, and lower DHEAS levels in comparison with c ontrols. Both ACTH and cortisol levels were not different in suppressor and nonsuppressor patients, but DHEAS levels were significantly lower in nonsu ppressor cases, who also exhibited ACTH and cortisol periodicities more alt ered than in suppressor and in control subjects. IGF-I and IGFBP-3 levels w ere lower and those of IGFBP-1 higher in nonsuppressor than in suppressor c ases and in healthy controls. IGF-I/IGFBPs system data were correlated with cognitive impairment and adrenal steroid levels in AD patients. (J. Endocr inol. Invest. 23: 178-186, 2000) (C) 2000, Editrice Kurtis.Alterations in t he hypothalamic-pituitary-adrenal axis (HPAA) and failure of dexamethasone (DXT) to suppress cortisol secretion occur in Alzheimer's disease (AD). Thi s study was aimed to settle possible differences in some clinical (age, bod y weight, body mass index, dementia severity) and hormonal parameters in AD patients non-responders to overnight 1 mg-DXT suppression test compared wi th the responder subjects. ACTH, cortisol and dehydroepiandrosterone sulpha te (DHEAS) day-time levels were assessed in 25 AD patients and in 12 age-ma tched healthy controls before DXT administration. In view of their neuropro tective effects, plasma levels of Insulin-like Growth Factor-I (IGF-I) and of IGF-Binding Proteins (IGFBPs) were also determined. After DXT, 8 AD subj ects (32%) showed cortisol levels above the conventional cut-off of 140 nmo l/L. No significant differences were found in clinical parameters in suppre ssor vs nonsuppressor patients. AD subjects showed higher cortisol, cortiso l/DHEAS ratios, and lower DHEAS levels in comparison with controls. Both AC TH and cortisol levels were not different in suppressor and nonsuppressor p atients, but DHEAS levels were significantly lower in nonsuppressor cases, who also exhibited ACTH and cortisol periodicities more altered than in sup pressor and in control subjects. IGF-I and IGFBP-3 levels were lower and th ose of IGFBP-1 higher in nonsuppressor than in suppressor cases and in heal thy controls. IGF-I/IGFBPs system data were correlated with cognitive impai rment and adrenal steroid levels in AD patients. (J. Endocrinol. Invest. 23 : 178-186, 2000) (C) 2000, Editrice Kurtis.