, Volume 60, Issue 3, pp 395–406 | Cite as

A score derived from routine biochemical parameters increases the diagnostic accuracy of chromogranin A in detecting patients with neuroendocrine neoplasms

  • Ivan Kruljac
  • Ivan Vurnek
  • Sebastian Maasberg
  • Davor Kust
  • Kristina Blaslov
  • Blaženka Ladika Davidović
  • Mario Štefanović
  • Alma Demirović
  • Alen Bišćanin
  • Jakša Filipović-Čugura
  • Jasmina Marić Brozić
  • Ulrich-Frank Pape
  • Milan Vrkljan
Endocrine Methods and Techniques



Chromogranin A (CgA) is a valuable biomarker for detection and follow-up of patients with neuroendocrine neoplasms (NENs). However, various comorbidities may influence serum CgA, which decreases its diagnostic accuracy. We aimed to investigate which laboratory parameters are independently associated with increased CgA in real-life setting and to develop a scoring system, which could improve the diagnostic accuracy of CgA in detecting patients with NENs.


This retrospective study included 55 treatment naïve patients with NENs and160 patients with various comorbidities but without NEN (nonNENs). Scoring system (CgA-score) was developed based on z-scores obtained from receiver operating curve analysis for each parameter that was associated with elevated serum CgA in nonNENs.


CgA correlated positively with serum BUN, creatinine, α2-globulin, red-cell distribution width, erythrocyte sedimentation rate, plasma glucose and correlated inversely with hemoglobin, thrombocytes and serum albumin. Serum CgA was also associated with the presence of chronic renal failure, arterial hypertension and diabetes and the use of PPI. In the entire study population, CgA showed an area under the curve of 0.656. Aforementioned parameters were used to develop a CgA-score. In a cohort of patients with CgA-score <12.0 (N = 87), serum CgA >156.5 ng/ml had 77.8% sensitivity and 91.5% specificity for detecting NENs (AUC 0.841, 95% CI 0.713–0.969, P < 0.001). Serum CgA had no diagnostic value in detecting NENs in patients with CgA-score >12.0 (AUC 0.554, 95% CI 0.405–0.702, P = 0.430).


CgA-score encompasses a wide range of comorbidities and represents a promising tool that could improve diagnostic performance of CgA in everyday clinical practice.


Chromogranin A Comorbidity Diagnostic accuracy Score Neuroendocrine neoplasm 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12020_2018_1592_MOESM1_ESM.pdf (65 kb)
Supplementary appendix


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ivan Kruljac
    • 1
  • Ivan Vurnek
    • 2
  • Sebastian Maasberg
    • 3
  • Davor Kust
    • 4
  • Kristina Blaslov
    • 1
  • Blaženka Ladika Davidović
    • 4
  • Mario Štefanović
    • 5
  • Alma Demirović
    • 6
  • Alen Bišćanin
    • 7
  • Jakša Filipović-Čugura
    • 8
  • Jasmina Marić Brozić
    • 4
  • Ulrich-Frank Pape
    • 3
  • Milan Vrkljan
    • 1
  1. 1.Department of Endocrinology, Diabetes and Metabolic Diseases “Mladen Sekso”University Hospital Center “Sestre Milosrdnice”, University of Zagreb School of MedicineZagrebCroatia
  2. 2.University of Zagreb School of MedicineZagrebCroatia
  3. 3.Department of Hepatology and Gastroenterology, ENETS Center of Excellence for Neuroendocrine Tumors, Charité Campus Mitte and Virchow ClinicCharité University MedicineBerlinGermany
  4. 4.Department of Oncology and Nuclear MedicineUniversity Hospital Center “Sestre Milosrdnice”ZagrebCroatia
  5. 5.Clinical Institute of ChemistryUniversity Hospital Center “Sestre Milosrdnice”, University of Zagreb Faculty of Pharmacy and BiochemistryZagrebCroatia
  6. 6.Department of PathologyUniversity Hospital Center “Sestre Milosrdnice”, University of Zagreb School of MedicineZagrebCroatia
  7. 7.Department of Gastroenterology and HepatologyUniversity Hospital Center “Sestre Milosrdnice”ZagrebCroatia
  8. 8.Department of SurgeryUniversity Hospital Center “Sestre Milosrdnice”ZagrebCroatia

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