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Cited by 60Neuroendocrine Tumor Research AdvancesClinical Laboratory Practices and Quality ControlPituitary Gland Disorders and Treatments

Effect of Short-Term Proton Pump Inhibitor Treatment and Its Discontinuation on Chromogranin A in Healthy Subjects

Mosli, Hala H., Dennis, Alan, Kocha, Walter, Asher, Linda J., Van Uum, Stan H. M.·2012·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2012-1548
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Abstract

CONTEXT: Chromogranin A (CgA) is used as a generic tumor marker for neuroendocrine tumors. Proton pump inhibitors (PPI) are known to increase CgA, but it is not clear to what extent, and there is little information on how long PPI need to be discontinued before the effect of PPI has disappeared. Furthermore, is it not known whether this PPI effect is dependent on the CgA assay used. OBJECTIVE: The aim of the study was to determine the effect of 7-d treatment with a PPI and its discontinuation on CgA in serum and plasma comparing four CgA assays. DESIGN AND PARTICIPANTS: Seventeen healthy subjects took lansoprazole 30 mg at bedtime for 7 d, and blood samples for CgA were obtained at baseline, d 7 of PPI use, and 1, 2, 4, and 7 d after discontinuation of the PPI. In all samples, CgA was measured using the following assays: Alpco (serum and plasma), Cis-Bio (serum and plasma), DAKO, and Cis-Bio radioisotope assay. RESULTS: When using the same assay, CgA was higher in plasma than in serum. Treatment with a PPI for 1 wk resulted in a significant (about 2.5-fold) increase in CgA with significant interindividual variation. After discontinuation of PPI, serum CgA gradually declined, with a half-life of 4-5 d. CONCLUSION: Short-term PPI use results in a significant increase of CgA in serum and plasma, an effect that is largely independent of the assay used. PPI need to be discontinued for 2 wk to fully eliminate their effect on CgA. This effect of PPI needs to be considered when interpreting results of CgA measurements.

Integrity signals

Registry

Crossref · 10.1210/jc.2012-1548

Cites

15 of 15 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

7 of 18 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Proton pump inhibitors (PPI) and histamine H2-receptor blockers are important factors influencing CgA concentrations.

    “One important factor is gastric acid suppressive therapy by proton pump inhibitors (PPI) and histamine H 2 -receptor blockers (4, 5).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [4] Waldum, 1996, Marked increase in gastric acid secretory capacity after omeprazole treatment., Gut source

      The Abstract and the section on plasma gastrin report that serum CgA increased during omeprazole treatment, supporting the PPI part of the claim. The paper mentions H2 blockers in relation to acid secretion, but does not report that they influence CgA concentrations. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [5] Glinicki, 2010, Chromogranin A (CgA)—the influence of various factors in vivo and in vitro, and existing disorders on it's concentration in blood., Endokrynol Pol

      Not checked in the free run.

  • Findingown data

    Treatment with a PPI for 1 week resulted in a significant increase in CgA for all assays.

    “Treatment with a PPI for 1 wk resulted in a significant increase in CgA for all assays (Table 1).”
    • Also stated in: § Discussion · plain
      “PPI treatment for only 1 wk resulted in a significant increase of CgA concentrations in both serum and plasma”
    Quote in the paperSubstantial claim
  • Findingown data

    The half-life of CgA based on the decline after PPI discontinuation varied between 3.7 and 4.9 days for all assays.

    “The half-life of CgA based on the decline after PPI discontinuation varied between 3.7 and 4.9 d for all assays.”
    • Also stated in: § Abstract · plain
      “with a half-life of 4 -5 d.”
    Quote in the paperSubstantial claim
  • Findingown data

    When using the same assay, serum CgA results were lower than plasma results, particularly for the Alpco assay.

    “when using the same assay, the serum results were lower than the plasma results, particularly for the Alpco assay.”
    • Also stated in: § Discussion · hedged
      “At baseline, the CgA levels appeared to be higher in plasma than in serum, independently of the method used (immunoradiometric assay or ELISA).”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was a large interindividual variation in the increase of CgA after PPI intake, ranging from almost no increase to a 10-fold increase.

    “There was a large interindividual variation in the increase of CgA after PPI intake.”
    • Also stated in: § Discussion · plain
      “the actual increase in CgA during PPI varied hugely between individuals from almost no increase to a 10fold increase.”
    Quote in the paperSubstantial claim
  • May combine two claims. 10
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Premisecitation

    Short-term application of PPI stimulates ECL cell function, and prolonged gastric acid suppression results in hyperplasia of enterochromaffin-like cells in the gastric mucosa.

    “Short-term application of PPI stimulates ECL cell function, and prolonged gastric acid suppression results in hy-perplasia of the enterochromaffin-like cells in the gastric mucosa (6).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [6] Kuipers, 2006, Proton pump inhibitors and gastric neoplasia., Gut source

      In the paper’s discussion of PPIs and gastric carcinoids (page not available in our copy), prolonged acid suppression is linked to enterochromaffin-like cell hyperplasia in rats, and apparent hyperplasia is reported in 10–30% of chronic human PPI users. The passage cautions that the human finding may reflect cell clustering rather than an actual increase. Our copy does not state that short-term PPI use stimulates ECL-cell function. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Chromogranin A (CgA) is used as a generic tumor marker for neuroendocrine tumors.

    “CgA has emerged as a generic tumor marker for neuroendocrine tumors (NET) (1,2).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] Nobels, 1998, Chromogranin A: its clinical value as marker of neuroendocrine tumours., Eur J Clin Invest source
    • cites [2] Massironi, 2008, Neuroendocrine tumors of the gastro-entero-pancreatic system., World J Gastroenterol source

  • Classified as probably not a substantial claim.

    Interpretationcitation

    PPI may need to be discontinued to obtain reliable CgA results, especially when CgA elevation was unexpected.

    “Therefore, PPI may need to be discontinued to obtain reliable CgA results, especially when CgA elevation was unexpected (13).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] Korse, 2011, Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours., Br J Cancer source
    • Rests on an assumption: The effect of PPI on CgA observed in healthy subjects applies to patients with neuroendocrine tumors.

  • May combine two claims.

    Premisecitation

    The effect of short-term PPI therapy on CgA levels has not been studied systematically, and there is very little information on the duration of the effect of PPI on CgA levels.

    “However, the effect of short-term PPI therapy on CgA levels has not been studied systematically, and there is very little information on the duration of the effect of PPI on CgA levels, and thus on how long PPI need to be stopped before their effect on CgA has disappeared.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [8] Kim, 2009, Influence of long-term gastric acid suppression therapy on the expression of serum gastrin, chromogranin A, and ghrelin., Korean J Gastroenterol source

      The retrieved passages are from an Irritable Bowel Syndrome references section (page unavailable), not a discussion of PPI therapy or CgA. Searches for short-term PPI effects, CgA, and the duration of effects after stopping PPIs found no passage in our copy that addresses the claim. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [9] Giusti, 2004, Effect of short-term treatment with low dosages of the proton-pump inhibitor omeprazole on serum chromogranin A levels in man., Eur J Endocrinol source

  • May combine two claims.

    Premisecitation

    Vezzosi et al. studied 184 NET patients and found 130 elevated CgA results; at least one false-positive CgA result was found in 99 patients, mostly caused by PPI therapy and impaired kidney function.

    “Vezzosi et al. (12) studied 184 NET patients and found 130 elevated CgA results.At least one false-positive CgA result was found in 99 patients, mostly caused by PPI therapy and impaired kidney function.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [12] Vezzosi, 2011, Chromogranin A measurement in metastatic well-differentiated gastroenteropancreatic neuroendocrine carcinoma: screening for false positives and a prospective follow-up study., Int J Biol Markers source

      The results (p. 96) report elevated CgA in 130 of 184 patients; 99 of those 130 had a condition that could raise CgA, chiefly renal failure or proton-pump inhibitor treatment. The paper does not establish that all 99 had a false-positive result: it says the contribution of those conditions relative to tumor secretion remains uncertain. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Korse et al. studied patients with well-differentiated NET with unexpectedly high CgA; PPI discontinuation resulted in an 82% decrease of CgA in patients without NET tumor burden and about a 50% decrease in patients with tumor burden.

    “Korse et al. (13), who studied patients with well-differentiated NET with an unexpectedly high CgA.PPI discontinuation resulted in an 82% decrease of CgA in patients without NET tumor burden and about a 50% decrease in patients with tumor burden.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] Korse, 2011, Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours., Br J Cancer source

      The Materials and methods and Results describe patients with well-differentiated NET and unexpectedly elevated CgA. The Results report that median CgA fell from 390 to 56 μg/l in patients with no evidence of disease and from 618 to 318 μg/l—about 49%—in patients with stable disease. The reported 82% decrease, however, applies to all 12 patients who stopped acid inhibition completely, not specifically to those without tumour burden. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    During the washout period, CgA concentrations gradually declined, and 1 week after discontinuation they were close to baseline but had not fully returned to baseline.

    “During the washout period, the CgA concentrations gradually declined, and 1 wk after discontinuation they were close to baseline, but had not fully returned to baseline.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The increase in CgA after 1 week of PPI was about 2.5-fold for most assays, with a lower about 1.5-fold increase as measured by the Cis-Bio Isotope method.

    “The increase was about 2.5-fold for most assays, with a lower (about 1.5fold) increase as measured by the Cis-Bio Isotope method.”
    • Also stated in: § Discussion · plain
      “we found an increase of about 2.5-fold based on most assays.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Short-term PPI use results in a significant increase of CgA in serum and plasma, an effect that is largely independent of the assay used.

    “Short-term PPI use results in a significant increase of CgA in serum and plasma, an effect that is largely independent of the assay used.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Enterochromaffin-like cells are the main source for gastric CgA expression and, under the influence of gastrin, exhibit enhanced transcription of the CgA gene resulting in increased CgA synthesis.

    “These cells are the main source for gastric CgA expression and, under the influence of gastrin, exhibit enhanced transcription of the CgA gene resulting in increased CgA synthesis (7).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] Cramer, 2008, Gastrin transactivates the chromogranin A gene through MEK-1/ERK- and PKC-dependent phosphorylation of Sp1 and CREB., Cell Signal source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study had a prospective design.

    “Strengths of our studies include the prospective design”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    The number of participants was small, and the participants were healthy subjects without neuroendocrine tumors.

    “the number of participants was small, and the participants were healthy subjects without NET.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The prospective nature of the study allowed determination of the increase of CgA compared with baseline within individuals.

    “The prospective nature of our study allowed us to determine the increase of CgA compared with baseline within individuals”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study was registered at ClinicalTrials.gov with identifier NCT01216267.

    “The study was registered at www.ClinicalTrials.gov(identifier: NCT01216267).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study had frequent sampling after PPI discontinuation.

    “the frequent sampling after PPI discontinuation”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study used multiple CgA assays.

    “the use of multiple CgA assays”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All participants provided written informed consent.

    “All participants provided written informed consent.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The timing of PPI administration in the evening in the study could have influenced the results.

    “the timing of the PPI administration in the evening in our study could have influenced our results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was approved by the Health Sciences Research Ethics Board of the University of Western Ontario.

    “The study was approved by the Health Sciences Research Ethics Board of the University of Western Ontario.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Because of large interindividual variation in the effect of PPI on CgA, one cannot simply predict the effect of PPI on CgA concentration, and discontinuation of PPI may be required to determine the effect in an individual patient.

    “Because of this large interindividual variation in the effect of PPI on CgA, one cannot simply predict the effect of the PPI on CgA concentration, and discontinuation of the PPI may be required to determine the effect in the individual patient.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    CgA assays vary in their specificity for the part(s) of the CgA molecule being measured, which may result in variation in the effects of PPI on CgA.

    “Furthermore, CgA assays vary in their specificity for the part(s) of the CgA molecule being measured, which may result in variation in the effects of PPI on CgA.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous studies had found a similar effect of longer-term gastric acid suppression with PPI, ranging from 6 weeks to longer than 1 year.

    “Previous studies had found a similar effect of longer-term gastric acid suppression with PPI, ranging from 6 wk to longer than 1 yr (11).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Sanduleanu, 2001, Serum chromogranin A as a screening test for gastric enterochromaffin-like cell hyperplasia during acid-suppressive therapy., Eur J Clin Invest source
22 of 22

  • The paper relies on this without support.

    The effect of PPI on CgA observed in healthy subjects applies to patients with neuroendocrine tumors.

    “the participants were healthy subjects without NET.”
    “The CgA increasing effect of PPI can result in falsepositive CgA results in patients with NET.”

  • The paper relies on this without support.

    After the 1-week washout observation, CgA continues to decline at the same rate such that 2 weeks is sufficient to eliminate the PPI effect.

    “1 wk after discontinuation they were close to baseline, but had not fully returned to baseline.”
    “Discontinuation of PPI for 2 wk is required to eliminate the PPI effect on CgA, even after its short-term use.”
2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Plasma-serum comparison is attributed to an assay used only on plasma

    Minor

    The discussion says the baseline plasma-serum difference was observed independently of whether an immunoradiometric assay or ELISA was used. The methods state that the immunoradiometric assay was used only on plasma, so it could not establish that comparison.

  • Reported maximum increase conflicts with the table

    Minor

    The discussion describes increases reaching a 10-fold maximum, but the table reports a value of 2065% of baseline for one subject-more than 20-fold.

2 of 2

Cites

Flagged first, then by citations

2 of the 17 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Mosli, H. H., Dennis, A., Kocha, W., Asher, L. J., & Van Uum, S. H. M.
Affiliations
  • Western University (CA)
  • London Laboratory Services Group (A.D.), London, Ontario, Canada N6A 5W9
  • London Health Sciences Centre (CA)
  • Lawson Health Research Institute (S.H.M.V.U.), Western University, London, Ontario, Canada N6A 4V2
ORCID
Mosli, Hala H.
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2012-09-01
Volume
97
Issue
9
Pages
E1731-E1735
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2012-1548
OpenAlex
W2023059943
Cited by
59
References
17
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 1
FWCI
4.06
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
chromogranin A, proton pump inhibitors, lansoprazole, PPI discontinuation, neuroendocrine tumor markers, healthy volunteers
MeSH terms
Adolescent, Adult, Aged, Enzyme-Linked Immunosorbent Assay, Female, Half-Life, Histamine H2 Antagonists, Humans, Male, Middle Aged, Biomarkers, Tumor, Chromogranin A, 2-Pyridinylmethylsulfinylbenzimidazoles, Proton Pump Inhibitors, Young Adult, Lansoprazole

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Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

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