Hypofunction of the sympathetic nervous system is an etiologic factor for a wide variety of chronic treatment-refractory pathologic disorders which all respond to therapy with sympathomimetic amines.

The hypothesis set forth is that the basis for a great many chronic debilitating conditions that involve almost all of the physiologic systems of the body may have as the underlying cause and a common link between them, i.e., hypofunction of the sympathetic nervous system. The hypothesis considers that one of the main functions of the sympathetic nervous system is to diminish cellular permeability. Thus sympathetic hypofunction may lead to absorption of chemicals and toxins into tissues that were supposed to be impervious leading to inflammation and other adverse consequences which then cause a wide variety of symptoms. These symptoms may include pain or diminished muscular function leading to various pain syndromes or conditions related to diminished muscular function. Furthermore since the sympathetic nervous system is involved in body homeostasis and temperature regulation, sympathetic nervous system hypofunction could lead to disorders in these areas, e.g., vasomotor symptoms and edema. This defect in sympathetic nervous system has a genetic predisposition but relatives, e.g., siblings or children may manifest in a different manner which suggests some influence of external factors causing one physiological system to be more prone than another to malfunction under conditions of sympathetic hypofunction. Evidence to support this hypothesis has been provided by a large number of published anecdotes demonstrating the quick and long lasting considerable improvement in symptoms following treatment with the sympathomimetic amine dextroamphetamine sulfate (with return of symptoms if treatment is temporarily ceased thus diminishing the likelihood of spontaneous remission) despite failure to respond to a plethora of other pharmacologic agents and other therapies over many years. The physiological systems with various chronic disorders that have responded included the gastrointestinal system, skin, genitourinary system, the nervous system, the musculoskeletal system, the temperature regulation system, peripheral vasculature system, and the endocrine system. Despite the multitude of very convincing anecdotal reports showing its efficacy (and to date no reports refuting this hypothesis), there has only been one controlled study which showed the benefit of dextroamphetamine sulfate on edema and weight gain in diet-refractory patients. The flaw to date for general acceptance of this hypothesis is that most positive studies are coming from one clinical center. Furthermore, more controlled studies are needed. There has been a recent interest amongst physiologists and recent studies have been published confirming a deficiency of sympathetic nerve fibers in some of these disorders which hopefully will encourage more research into other physiologic systems leading to corroboration of this hypothesis.