Background: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. Methods: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. Results: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0–127.4) in non-NENs and 13.8% (0.0–43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. Conclusions: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

Background Physiological agents are strictly regulated within the reference range. Any deviation from that range is considered to be a disruption of homeostasis and a potentially harmful process. However, it has been reported that finite alterations of several physiological agents may behave according to a nonlinearity described as the mirror‐J‐shaped curve. Namely, small deviations from the reference range produce a positive (beneficial) effect, whereas larger deviations of the same physiological agents produce a negative (harmful) effect. Certain clinical trials and basic research data support such concept. These hormetic effects have been described for the physiological agents oscillations of glucose, oxygen, calcium, calories, osmolality, etc. It thus appeared as a more general physiological phenomenon. Hypothesis Mild acidosis and mild alkalosis may produce a beneficial physiological effect. Methods Research of published data that may support the concept of beneficial effects of mild acidosis and mild alkalosis. Results Mild acidosis has beneficial effects in various experimental and clinical settings, whereas stronger acidosis is regularly toxic. On a cellular level mild acidosis has been proven to prolong human neutrophil lifespan by induction of phosphorylation of Akt, ERK, and p38MAPK, and therefore stabilizing mitochondrial transmembrane potential, delaying mitochondrial permeability transition and apoptosis. The same mechanism was found in ischemia/reperfusion injury models in which induced acidosis during reperfusion attenuated mitochondria‐dependent apoptosis and reduced reperfusion injury. The positive effect of a mild acidosis was also found in models of ventilator‐induced lung injury where permissive hypercapnia exerted positive effects. Mild alkalosis may be physiologically beneficial. The positive effects of mild alkalosis are mostly found in human exercise studies. It has been shown there to potentiate lactate efflux and by doing so improving cellular metabolism. Extracellular alkalosis during exercise contributed to the preservation of intracellular‐to‐extracellular K+ gradient and therefore the stability of the muscle membrane, and overall performance. Mild metabolic alkalosis was also found to increase muscle glycolytic flux and H+ efflux and increased total work done along with decreased exercise‐induced muscle fatigue in humans. Conclusion Mild acidosis and alkalosis follow the principle of the mirror‐J‐physiology. This interpretation of counterintuitive studies results could be a step forward in our understanding of integral homeostasis and body adaptation. Expectedly, moderate and strong acidoses and alkaloses have been found harmful/toxic.