title: Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options.
abstract: Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI.
authors.affiliation: Neuroscience Graduate Program, Wake Forest Graduate School of Arts and Sciences, Winston-Salem, North Carolina; Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Wagoner
authors.affiliation: Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina;
authors.forename: Hossam A
authors.initials: HA
authors.lastname: Shaltout
authors.affiliation: Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina; and Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: John E
authors.initials: JE
authors.lastname: Fortunato
authors.affiliation: Neuroscience Graduate Program, Wake Forest Graduate School of Arts and Sciences, Winston-Salem, North Carolina; Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina; and ddiz@wakehealth.edu.
authors.forename: Debra I
authors.initials: DI
authors.lastname: Diz
mesh_terms: D000293:Adolescent; D000450:Aldosterone / Q000097:blood*; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000809:Angiotensins / Q000097:blood*; D062186:Arterial Pressure / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D002395:Catecholamines / Q000097:blood*; D002648:Child; D003971:Diastole; D004298:Dopamine / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000097:blood* / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D054971:Orthostatic Intolerance / Q000097:blood / Q000503:physiopathology; D054972:Postural Orthostatic Tachycardia Syndrome / Q000097:blood* / Q000503:physiopathology; D011446:Prospective Studies; D012083:Renin / Q000097:blood*; D013575:Syncope / Q000097:blood* / Q000503:physiopathology; D013599:Systole; D018667:Tilt-Table Test; D014667:Vasopressins / Q000097:blood*
chemical_list: D000809:Angiotensins; D002395:Catecholamines; D014667:Vasopressins; D000804:Angiotensin II; D000450:Aldosterone; D000803:Angiotensin I; D012083:Renin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine
keywords: arginine vasopressin; head-upright tilt test; orthostatic hypotension; orthostatic intolerance; postural orthostatic tachycardia syndrome