## 1 Introduction  
Chronic fatigue syndrome (CFS) is a debilitating biological medical condition (International Classification of Diseases, ICD-11 8E49 [1]) with no approved treatment. It is characterized by unexplained physical fatigue, cognitive problems (brain fog), and post-sectional malaise (PEM) [2]. CFS's etiology is controversial, and its underlying mechanisms are not properly understood [3]. Hypotheses of its pathophysiology include stress of the immune and neurobehavioral systems [4]. Dysregulation of the immune system and an altered hypothalamic-pituitary-adrenal (HPA) axis are recurrent findings in CFS [5]. As a heterogeneous disorder, the close focus and monitoring of an individual patient'ssymptoms geared towards the identification of subtypes and clustering are needed for personalized treatments. The most commonly referred cause of CFS is a viral infection, which is proposed to drive exhaustion of the immune system. Consistently, the literature supports a reduction in natural killer (NK) activity and anti-inflammatory cytokines, as well as increased levels of proinflammatory cytokines in CFS patients [6; 7]. NK activity seems to indicate immune deficiency, with potential stratification value [8]. A subgroup of subjects diagnosed with CFS present stress-induced CFS [9; 10]. Currently, there exists limited understanding regarding stress-related CFS. There is an association of early life exposure to stress in the development of CFS [11]. However, stressors during late adolescence or early adulthood (such as study/work-related stress) could also elicit CFS. The prevalence of stress-related CFS is unknown, and the exact onset mechanism remains unclear. However, the literature recognizes that stress can disrupt physiological systems and behaviors, contributing to the onset and perpetuation of CFS symptoms. The impact of perceived stress management on CFS symptoms has been studied, showing some benefits on physical symptoms such as PEM [12; 13]. The HPA axis appears to be dysregulated in patients with CFS, thus explaining several symptoms of the disease, including PEM. A subset of CFS patients present hypocortisolism at awakening [14], but proper stress management seems to regulate cortisol levels and PEM in CFS to a certain extent [13]. Functional alterations of the glucocorticoid receptor gene (NR3C1) have also been connected to CFS [15]. The main catecholamines, dopamine (DA) and noradrenaline (NA), play an important role in HPA function and the response to stress. Some CFS cases and individuals with postural orthostatic tachycardia syndrome (POTS) often present with a hyperadrenergic state [16; 17]. This \"sustained\" arousal may derive from a chronic response against infections as well as an adaptation to psychological stressors that interact with predisposing genetic or epigenetic factors [16]. Beta-adrenergic blockers are recommended for those cases [6; 18]. However, some CFS patients with specific genetic alterations show a better response to beta-blocker treatment than others [6; 19]. Main catecholamine regulators, such as the catechol-O-methyltransferaseerase (COMT), have been shown to play an important role in CFS. A genetic variation in COMT has been recognized in a subset of CFS patients [19; 20]. In addition to genetic factors, epigenetic modifications, such as differential DNA methylation at loci associated with differences in, for example, glucocorticoid sensitivity [5] or the COMT gene [21], may be important as biomarkers for future clinical testing of CFS. The current case report follows the CARE guidelines for case reports [22]. We introduce a male patient (body weight 76-82 kg; height 185 cm) diagnosed with CFS in 2012 (Center for Disease Control (CDC/Fukuda) [2]), and recognized as a stress-related CFS case. Owing to the scarcity of studies specifically addressing this subgroup of CFS patients, the data acquired from the current patient are exceptionally valuable, contributing to an enhanced understanding of the underlying mechanisms involved in stress-related CFS.