Flushing: Neuroendocrine Mechanisms and a Structured Diagnostic Approach

INTRODUCTION: Flushing is a common clinical symptom characterised by transient cutaneous vasodilation and erythema, frequently accompanied by a sensation of heat. Although often benign, it may signal endocrine, neuroendocrine, autonomic, inflammatory, pharmacologic, or neoplastic disorders. OBJECTIVES: To provide an integrated review of the neuroendocrine and vascular mechanisms underlying flushing and to propose a structured, clinically applicable diagnostic approach based on symptom patterns and pathophysiological pathways. METHODS: A narrative review of the literature was conducted, focusing on thermoregulatory physiology, neuroendocrine signalling, vascular control, and clinical conditions associated with flushing. Evidence from experimental, observational, and clinical studies was synthesised to develop a mechanistic framework and a stepwise diagnostic algorithm integrating clinical features and targeted laboratory evaluation. RESULTS: Flushing arises from disruption of central thermoregulatory integration involving hypothalamic nuclei, peripheral sensory pathways, and vasoactive mediators, including oestrogens, serotonin, catecholamines, vasoactive intestinal peptide, prostaglandins, substance P, and histamine. Neurotransmitters help modulate the vascular response, which is further influenced by endothelial function and autonomic tone. CONCLUSIONS: Flushing is a multifactorial symptom reflecting integrated neuroendocrine and vascular dysregulation rather than an isolated cutaneous phenomenon. Recognising the distinction between wet and dry flushing and applying a mechanism-based diagnostic framework may improve diagnostic accuracy and facilitate earlier identification of clinically important underlying disorders.