Postural Tachycardia Syndrome in Children and Adolescents: Pathophysiology and Clinical Management

Iron is an essential element for numerous fundamental biologic processes, but excess iron is toxic. Abnormalities in systemic iron balance are common in patients with chronic kidney disease and iron administration is a mainstay of anemia management in many patients. This review provides an overview of the essential role of iron in biology, the regulation of systemic and cellular iron homeostasis, how imbalances in iron homeostasis contribute to disease, and the implications for chronic kidney disease patients.

Background Patients with postural tachycardia syndrome (POTS) have exaggerated orthostatic tachycardia often following a viral illness, suggesting autoimmunity may play a pathophysiological role in POTS. We tested the hypothesis that they harbor functional autoantibodies to adrenergic receptors (AR). Methods and Results Fourteen POTS patients (7 each from 2 institutions) and 10 healthy subjects were examined for α1AR autoantibody‐mediated contractility using a perfused rat cremaster arteriole assay. A receptor‐transfected cell‐based assay was used to detect the presence of β1AR and β2AR autoantibodies. Data were normalized and expressed as a percentage of baseline. The sera of all 14 POTS patients demonstrated significant arteriolar contractile activity (69±3% compared to 91±1% of baseline for healthy controls, P<0.001) when coexisting β2AR dilative activity was blocked; and this was suppressed by α1AR blockade with prazosin. POTS sera acted as a partial α1AR antagonist significantly shifting phenylephrine contractility curves to the right. All POTS sera increased β1AR activation (130±3% of baseline, P<0.01) and a subset had increased β2AR activity versus healthy subjects. POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced β1AR and β2AR agonist activity. Autoantibody‐positive POTS sera demonstrated specific binding to β1AR, β2AR, and α1AR in transfected cells. Conclusions POTS patients have elevated α1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of α1AR for vasoconstriction and concurrent βAR‐mediated tachycardia. Coexisting β1AR and β2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients.