Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders

Postural tachycardia syndrome ( POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation ( MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA ( MCA + POTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age- matched female controls. MCA + POTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long- term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia ( from 79 +/- 4 to 114 +/- 6 bpm), increased systolic blood pressure on standing ( from 117 +/- 5 to 126 +/- 7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver ( 157 +/- 12 versus 117 +/- 9 in normal controls and 119 +/- 7 mm Hg in POTS; P = 0.048), and an exaggerated phase IV blood pressure overshoot ( 50 +/- 10 versus 17 +/- 3 mm Hg in normal controls; P < 0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but beta- blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.