This refers to a phenomenon whereby normal stimuli or signals which are derived from the throat and transmitted to the brain undergo pathological processing in the central nervous system (CNS) during which the input is abnormally amplified. This information is translated into an unpleasant sensation such as globus (lump or tightness in the throat). Evidence for the mechanism of visceral hypersensitivity in patients with globus sensation is derived from well-designed clinical studies that assessed the response to esophageal balloon distention. From these studies it was demonstrated that compared with healthy controls, patients with globus sensation reported of symptoms at lower distending thresholds, suggesting the presence of esophageal hypersensitivity [4]. In another study, as compared with healthy controls, only patients with globus reported that during esophageal balloon distention they felt globus sensation in the suprasternal notch, suggesting that globus may represent an aberrant central processing of esophageal stimuli.

Patients with globus sensation have been assessed by stationary esophageal manometry in an attempt to find clues for a possible motoric dysfunction which might explain the occurrence of symptoms. Thus far, however, results have not shown any consistent evidence which attributes globus to malfunction of the upper esophageal sphincter (UES). There have been some reports of abnormal UES function such as hypercontractility of the UES (hypertensive UES). However, in more recent studies that employ high-resolution manometry (HRM), these findings were not confirmed, and researchers found no difference in UES mechanics between controls and those with globus sensation [5]. Recently, high-resolution manometry has revealed a number of patterns of UES pathology, including hyperdynamic upper esophageal sphincter inspiratory pressure and high upper esophageal sphincter post-swallow residual pressure among patients with globus. Although these might correlate with symptoms, there is no evidence that these findings are related to disease pathogenesis. Furthermore, in the face of a completely normal food-induced oropharyngeal swallowing process, the issue of a major esophageal motor disorder does not seem to be likely. The same holds true for an anatomic abnormality, including the cricopharyngeal bar, as the anatomy of the oropharyngeal cavity in patients with globus sensation is completely normal.

Globus may itself represent an atypical manifestation of the GERD spectrum and as a result more patients with globus sensation report also of reflux symptoms. For this reason GERD must be thoroughly excluded prior to establishing a diagnosis of globus sensation. According to the recent Rome IV consensus for the diagnosis of globus sensation (described below) even a potentially acid-producing esophageal inlet patch of heterotropic gastric mucosa precludes a diagnosis of globus sensation. Thus far a strong causal relationship between GERD and globus has not been established [6]. In fact, the response rate of globus sensation to PPI therapy is low and there is only anecdotal evidence that patients with globus are more likely than controls to have abnormal pH studies. Overall, it seems that GERD plays a minor role in the pathophysiology of globus meaning that if a PPI trial succeeds the diagnosis is GERD with globus and if not one should evaluate for other etiologies, mainly major esophageal motor disorder and psychological comorbidity that induces globus sensation.

Psychiatric illness, particularly anxiety and depression, is common in patients with globus sensation and may predispose, precipitate, exacerbate, or perpetuate symptoms. By using self-reported questionnaires that evaluate for neuroticism, introversion, anxiety, and depression, it was found that patients with globus sensation score higher than healthy controls [7, 8]. In addition, women with globus sensation demonstrated a higher prevalence of anxiety and somatic concerns [9–11]. However, despite the aforementioned observations, no specific psychological characteristic or specific “hysterical” personality traits have been identified in patients with globus. Thus, the commonly used term “globus hystericus ” is a misnomer and should no longer be applied [12]. Stressful life events that preceded the onset of globus have been reported in the literature, suggesting stress as a risk factor in globus generation or exacerbation [9]. In fact, acute stress has been reported in the majority (97%) of sufferers as a precipitating factor of globus exacerbation.

An association between chronic thyroiditis and globus sensation has been described in many observational studies. In a recent cohort of 92 subjects attending a thyroid clinic, 35% reported globus sensation and 39% had ultrasonographic evidence of chronic thyroiditis [13]. Overall, the risk of globus sensation was calculated as 3.7-fold higher in patients with chronic thyroiditis. Secondly, sleep disorders are associated with globus sensation. In a cohort of 3360 healthy volunteers, sleep disorders were present in a significantly higher proportion of those reporting globus sensation (23.7%), compared to 13.6% among those with globus sensation [14]. Thirdly, globus sensation can occasionally be a result of pharyngeal, laryngeal, or upper esophageal pathology, including cysts and benign or malignant neoplasms. For this reason a thorough examination by an ENT surgeon is the recommended first step for the investigation of globus sensation.