Abstract 3201: Pseudo-Pheochromocytoma: A New Autoimmune Hypertensive Syndrome
A 56 yr old female with poorly controlled type 1 diabetes mellitus was seen in 2000. Her blood pressure was 147/92 and higher. Moderate cardiomegaly was present and a diagnosis of diabetic cardiomyopathy with associated hypertension was established. One month later, she suffered a myocardial infarction, cardiac arrest with resuscitation, and increased cardiac and renal failure requiring hemodialysis. Medications included a β blocker, converting enzyme inhibitor (CEI), and loop diuretic; recently a combined β blocker and central α2 agonist have sufficed. Sera from 2000 (prior to infarction) and from 2006 were positive at titers of 1:12,600 and 1:3,600 respectively by ELISA against β1 adrenergic receptor (β1AR) overexpressed in Sf9 membranes. These sera also reacted with β2AR by ELISA. Sera (1:100) increased protein kinase A (PKA) activation by 35% and 34% respectively over control incubated in vitro with H9c2 heart cells; equivalent to the isoproterenol positive control. The 2000 sera (1:100) increased spontaneous action potentials 40% over baseline in a canine Purkinjie fiber preparation. The serum increased the amplitude and configuration of the action potential in an isolated paced canine cardiomyocyte preparation. This patient, representative of four other patients with diabetic cardiomyopathy, has activating autoantibodies directed against β1AR and β2AR. There is no clinical evidence for a pheochromocytoma. The ease of blood pressure control with combined β-blockade supports the concept that the patient’s blood pressure is in part maintained by the β-agonist effect (but not α1) of the circulating autoantibodies. Anti-βAR activating autoantibodies also occur in idiopathic dilated cardiomyopathy and Chagas disease. Since the cardiac output decreases with development of cardiac damage in these patients, the stimulatory effects of the autoantibodies on the heart and circulation are masked and the blood pressure may normalize. This patient represents a new form of autoimmune-mediated hypertension not unlike a pheochromocytoma secreting primarily epinephrine. This new hypertensive syndrome should be considered in the differential diagnosis of mild hypertension associated with diabetes mellitus and cardiomyopathy.