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: