- AIMS: To determine whether central serotoninergic system activity is impaired by orthostatic challenge in patients with neurocardiogenic syncope (NCS). METHODS AND RESULTS: Thirty-five [mean age: 24 (SD): 6 years] patients with a clinical history of NCS and positive head-up tilt test and 35 age-matched healthy volunteers (CON = 25+/-5 years) with negative response were studied. Overnight dexamethasone suppression test (DST) (1.5 mg given at 11 p.m.) was performed to assess the sensitivity of the hypothalamic-pituitary-adrenal axis by measuring next day cortisol (microg/dL) at 8 a.m. and 4 p.m. Cardiac autonomic function, cortisol, and prolactin (ng/dL) were also determined at baseline supine (BAS) and after 5, 10, and 15 min of orthostatic stress (OS) at 60 degrees . No significant differences were observed in cortisol plasma levels after the DST: CON = 0.6+/-0.6 microg/dL vs. NCS = 0.6+/-0.5; P = 0.7. Cardiac autonomic function, cortisol, and prolactin responses were similar in both study groups (CON vs. NCS; P > 0.05) during BAS: cortisol = 8.6+/-4 vs.8.7+/-4 microg/dL and prolactin = 16.8+/-9 vs. 16.8+/-9 ng/dL; OS-5: cortisol = 8.7+/-5 vs. 8.5+/-4 microg/dL and prolactin = 16.9+/-9 vs. 15.8+/-9 ng/dL; OS-10: cortisol = 8.5+/-5 vs. 8.1+/-3 microg/dL; prolactin = 16.2+/-9 vs. 15.8+/-9 ng/dL, and OS-15: cortisol = 9.0+/-5 vs. 8.4+/-4 microg/dL; prolactin = 17.1+/-9 vs. 15.5+/-9 ng/dL. CONCLUSION: Central serotoninergic response during orthostatic challenge was not impaired in patients with recurrent NCS. These findings suggest that the activation of the hypothalamic-pituitary-adrenal axis is not altered in patients with recurrent NCS.