This monograph, which was more than five years in preparation, represents a very detailed account of pheochromocytoma, a tumor that is almost invariably lethal if untreated. In addition to its definitive presentation of the subject, this volume contains the most cur­ rent information regarding the diagnosis and management of pheochromocytoma. It is im­ portant to reemphasize the seriousness of diagnosing and treating pheochromocytoma with the aphorism of Esperson and Dahl­ Iversen that although a pheochromocytoma may be morphologically benign it is physio­ logically malignant (280) and with Aranow's characterization of this tumor as a "veritable pharmacological bomb" (20). If managed ap­ propriately by a highly skilled and profes­ sional "bomb squad," this tumor can be re­ moved and the patient cured in at least 90 percent of cases. The secret lies in first sus­ pecting and recognizing the patient who has and then offering the ex­ pheochromocytoma pert management such a patient requires. These facts more than justify this publication, since the internist, pediatrician, obstetrician, ophthalmologist, otolaryngologist, urologist, neurologist, surgeon, anesthesiologist, derma­ tologist, psychiatrist, radiologist, and also the dentist must be made acutely aware of the varied manifestations of this condition and of the pathologic entities which sometimes co- xiv Preface exist with pheochromocytoma. Furthermore, have included a large number of instructive they should have a thorough knowledge of the figures and have emphasized teaching tables.

1 Background and Importance.- Magnitude of the Hypertensive Problem.- Incidence of Pheochromocytoma.- Historical.- 2 Catecholamine Metabolism: Biosynthesis, Storage, Release, and Inactivation.- General Remarks.- Nomenclature, Occurrence, and Metabolism.- Sympathetic Nerves.- Biosynthesis, Storage, and Release of Norepinephrine.- Inactivation of Norepinephrine.- Catabolism.- Uptake and Binding.- Reuptake Mechanism.- Chromaffin Cells.- Biosynthesis, Storage, Release, and Inactivation.- Pheochromocytomas.- Biosynthesis.- Concentration of Biogenic Amines, Metabolites, and Dopa.- Differences between Adrenal Medulla and Pheochromocytoma in Storage, Release, and Inactivation of Catecholamines.- 3 Origin, Pathopharmacology, and Pathology.- Nomenclature.- Extraadrenal Paragangliomas of Uncertain Classification.- Carotid Body Paraganglioma.- Jugular Paraganglioma.- Laryngeal Paraganglioma.- Supraaortic and Aorticopulmonary Paragangliomas.- Pulmonary Paraganglioma.- Orbital Paraganglioma.- Intravagal Paraganglioma.- Comment.- Embryology.- Etiology (Sporadic and Familial).- Age of Occurrence and Sex Predilection.- Location.- Weight and Size.- Physiologic and Pharmacologic Effects.- Gross and Microscopic Appearance.- Ultrastructure.- Malignant Pheochromocytoma.- Pathologic Complications.- 4 Clinical Manifestations.- Frequency and Occurrence of Attacks.- Symptoms.- Headaches.- Excess Sweating.- Palpitations, Tachycardia, and Bradycardia.- Anxiety, Tremulousness, Nausea, Vomiting, and Faintness.- Chest and Abdominal Pain.- Weakness, Fatigue, and Prostration.- Weight Loss.- Dyspnea.- Warmth and Heat Intolerance.- Visual Disturbance.- Constipation.- Paresthesias and Pain in Extremities.- Grand Mal.- Miscellaneous.- Signs.- Hypertension (Sustained and/or Paroxysmal).- Orthostatic Hypotension.- Postural Tachycardia.- Paradoxic Blood Pressure Response.- Generalized Sweating.- Tachycardia and Reflex Bradycardia.- Pallor and Flushing.- Anxiety.- Retinopathy.- Weight Loss.- Tremor.- Raynaud's Phenomenon.- Fever.- Neurofibromatosis.- Palpable Mass in the Abdomen or Neck.- Swelling of the Thyroid Gland.- Miscellaneous.- Apnea or Tachypnea.- Heart Murmurs and Bruits.- Growth Defects.- Signs of Complications.- Circulatory Shock.- Gastrointestinal Disturbances.- Miscellaneous.- Atypical Manifestations.- Pheochromocytoma in Children.- Pheochromocytoma in Pregnancy.- Pheochromocytoma of the Urinary Bladder.- Pathologic Entities Sometimes Associated with Pheochromocytoma.- Cholelithiasis.- Medullary Thyroid Carcinoma.- Hyperparathyroidism.- Multiple Endocrine Neoplasia, Type 2 and Type 3.- Cushing's Syndrome.- Adrenal Virilism.- Addison's Disease.- Neurocutaneous Lesions.- Neurofibromatosis.- Mucosal Neuromas.- von Hippel-Lindau Disease.- Acromegaly.- Miscellaneous.- 5 Differential Diagnosis.- General Remarks.- Hypertension.- Anxiety or Psychiatric Disorder.- Hyperthyroidism.- Paroxysmal Tachycardia (Atrial and Nodal).- Hyperdynamic ?-Adrenergic Circulatory State.- Menopause.- Vasodilating Headaches.- Migraine Headache.- Cluster Headache.- Coronary Insufficiency Syndrome.- Acute Hypertensive Encephalopathy.- Diabetes Mellitus.- Renal Parenchymal or Renal Arterial Disease with Hypertension.- Focal Arterial Insufficiency of the Brain.- Intracranial Lesions (With or Without Increased Intracranial Pressure).- Autonomic Hyperreflexia.- Diencephalic Seizure (Autonomic Seizure or Epilepsy; Visceral Seizures) and Syndrome.- Toxemia of Pregnancy (Preeclampsia and Eclampsia).- Hypertensive Crises and Monoamine.- Oxidase Inhibitors.- Carcinoid Tumors.- Hypoglycemia.- Mastocytosis.- Familial Dysautonomia (Riley-Day Syndrome).- Acrodynia ("Pink Disease").- Neuroblastoma, Ganglioneuroblastoma, and Ganglioneuroma.- Acute Infectious Disease.- Rare Causes of Paroxysmal Hypertension.- Acute Intermittent Porphyria.- Acute or Chronic Lead Poisoning.- Tabetic Crisis in Tabes Dorsalis.- Acute Encephalitis.- Clonidine Withdrawal.- Hypovolemia with Inappropriate Reflex Vasoconstriction.- Fibrosarcoma of the Pulmonary Artery.- Pork Ingestion.- Hypothalamic Dysregulation.- Tetanus.- Guillain-Barré Syndrome.- Factitious Production of Paroxysmal Hypertension.- Fortuitous Circumstances Simulating Pheochromocytoma.- Potential Secondary Diagnoses.- 6 Diagnosis.- General Remarks.- A Guide for Screening.- Pheochromocytoma "Pearls".- Laboratory Findings.- Blood Glucose, Glycosuria, and Glucose Tolerance.- Basal Metabolism.- Plasma Free Fatty Acids (FFA).- Serum Cholesterol.- Peripheral Blood Counts and Red Cell Volume.- Plasma and Total Blood Volume.- Blood Urea.- Proteinuria.- Plasma Renin and Aldosterone.- Chemical Abnormalities Due to Associated Conditions.- Electrocardiographic Changes.- Clinical.- Experimental.- Concluding Remarks.- Pharmacologic Tests in the Diagnosis of Pheochromocytoma.- Methods of Pharmacologic Testing.- Provocative Tests.- ?-Adrenergic Blocking Test.- Biochemical Tests.- Urine Assays.- Experience at National Institute of Health.- Experience at Mount Sinai Medical Center, New York City.- Experience at the Mayo Clinic.- Experience at the Cleveland Clinic.- Remarks Concerning the Excretion of Dopamine.- Effect of Diet and Drugs.- Authors' Views Regarding Diagnosis of Pheochromocytoma by Urine Assay.- Plasma Assays.- Results Using the Ethylenediamine Method Employed by Manger and Coworkers.- Results Using the Double-Isotope Method of Engelman and Portnoy.- Comment on Double-Isotope Method.- Results Using Modifications of the Trihydroxyindole Fluorometric Method for Assay of Plasma Catecholamines.- Effects of Pharmacologic Tests and Hypertensive Episodes on Blood Pressure and Plasma Catecholamines.- Preoperative Localization of Pheochromocytoma.- Radiographic Techniques.- Abdominal x-Rays.- Intravenous Pyelography and Survey Films.- Nephrotomography.- Computerized Axial Tomography.- Retroperitoneal Pneumography.- Angiography (Arteriography and Venography).- Unusual Radiologic Features.- Isotopic Localization of Adrenal Pheochromocytoma.- Chest, Neck, and Head x-Rays.- Radiologic Manifestations of Diseases Associated with or Complicating Pheochromocytoma.- Central Venous Blood Sampling for Catecholamine Assay.- 7 Studies on 38 Patients with Pheochromocytoma in Whom Catecholamines Were Determined.- Case Reports.- Special Case Report-Pheochromocytoma Masquerading as Eclampsia.- Major Complaints and Findings among Patients…