5.2. Biochemical Diagnostics
As outlined before, serotonin (5-HT), produced by NETs, plays a pivotal role in the pathogenesis of CaHD. Consequently, patients with CaHD exhibit serum platelet, serotonin, and urinary 5-Hydroxyindoleacetic acid (5-HIAA) levels that are 2 to 4 times higher than those without CaHD. The urinary 5-HIAA levels, in particular, have been correlated with CaHD progression and worsening echocardiographic findings.25 As the end metabolite of serotonin, 5-HIAA’s measurement in 24-hour urine samples is a reliable initial diagnostic approach for carcinoid syndrome, closely linked to the presence of carcinoid tumours. A level exceeding 300 mmol/24 h is indicative of a heightened risk for CaHD, highlighting the need for holistic patient evaluation.11,26 However, dietary factors and certain medications may influence 5-HIAA levels, necessitating dietary restrictions prior to testing to avoid false-positive results. Moreover, the prognostic value of posttreatment 5-HIAA levels, particularly a threshold of 100 mg/24 h, significantly aids in predicting CaHD progression, as confirmed through serial echocardiographic assessments.27
NT-proBNP, a neurohormone released in response to increased cardiac wall stress, serves as an antifibrotic agent in the myocardium. Its levels are markedly elevated in CaHD patients compared to those without CaHD, making it an extremely useful biomarker for evaluating CaHD severity and prognosis. The high sensitivity and specificity of NT-proBNP in predicting CaHD underscore its utility in the clinical setting, particularly as a screening tool recommended by the UK and Ireland NET Society guidelines.28 This correlation is substantiated by echocardiographic evaluations, advocating for regular 6- to 12-month clinical assessments of NT-pro-BNP levels to monitor for valvular disease or heart failure signs.15 Moreover, plasma activin A levels are significantly higher in NET patients with CaHD, serving as an independent predictor for CaHD presence. Activin A stands out as an independent predictor for CaHD, demonstrating an 87% sensitivity and 57% specificity at plasma levels of ≥0.34 ng/ml.29 This marker’s elevation across both early and advanced stages of CaHD positions it as a critical indicator for early disease detection, offering a distinct advantage over traditional markers such as neuropeptide K, substance P, and atrial natriuretic peptide, which are typically associated with later stages of CaHD.30 Unlike NT-proBNP, elevated activin A levels are also found in CaHD patients without right heart dilatation, offering a broader diagnostic scope. Elevated levels of Connective Tissue Growth Factor (CTGF) have also been associated with reduced right ventricular function in NET patients with CaHD, providing another layer of diagnostic and prognostic information.31 Lastly, despite Chromogranin A’s broad application as a biomarker for NETs and CaHD, its utility in CaHD screening is limited by lower sensitivity and specificity. Nonetheless, it emerges as a vital follow-up tool for detecting carcinoid recurrence, boasting a sensitivity of 100% for CaHD.26
Treatment: