Autonomic dysfunction in systemic diseases: a narrative review

Purpose: Autonomic dysfunction is a common but frequently overlooked manifestation of systemic diseases. Because early manifestations are often nonspecific, including dizziness, fatigue, palpitations, exercise intolerance, and gastrointestinal dysmotility, clinicians need a structured approach to support timely recognition and risk stratification.Current concepts: Systemic disorders affect autonomic regulation through overlapping mechanisms, including metabolic injury, microvascular dysfunction, chronic inflammation, and impaired cardiovascular reflex control. In diabetes, autonomic nerve injury accumulates over time, and cardiovascular autonomic neuropathy is associated with increased cardiovascular events and mortality. In chronic kidney disease, persistent sympathetic activation, reduced vagal modulation, and baroreflex impairment contribute to hypertension, intradialytic hypotension, and arrhythmic risk. In heart failure and ischemic heart disease, sympathetic predominance and vagal withdrawal accelerate disease progression and are associated with malignant ventricular arrhythmias and sudden cardiac death. Systemic autoimmune disorders are also associated with impaired cardiovascular reflex control and small-fiber neuropathy.Discussion and conclusion: A practical evaluation begins with symptom screening and review of medications and comorbidities, followed by standardized autonomic testing. Cardiovascular autonomic reflex tests, together with scoring tools such as the composite autonomic scoring scale, help quantify the distribution and severity of autonomic involvement and support longitudinal monitoring. Management should integrate optimal control of the underlying systemic disease, non-pharmacological measures for orthostatic intolerance, and symptom-directed treatment for orthostatic hypotension.