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; Uum, Stan H. M. Van

doi:10.1210/jc.2012-1548

Cited by 51 publications

(48 citation statements)

References 13 publications

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“…CgA is a difficult test to use effectively in practice; there are multiple causes of false positives (most notably the use of proton pump inhibitors [10], but also coexisting renal or liver disease [11], heart failure[12], and inaccuracies in assays), and a false elevation in the surveillance setting can create great patient anxiety and result in multiple follow-on investigations. Research focusing on the utility of CgA in detecting early tumour recurrence is needed, and there is a pressing need to discover more specific predictive biomarkers for NETs.…”

Section: Discussionmentioning

confidence: 99%

Follow-Up for Resected Gastroenteropancreatic Neuroendocrine Tumours: A Practice Survey of the Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) and the North American Neuroendocrine Tumor Society (NANETS)

et al. 2018

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Objectives: There is no consensus regarding optimal follow-up in resected gastroenteropancreatic neuroendocrine tumours (NETs). We aimed to perform a practice survey to ascertain follow-up patterns by health care practitioners and highlight areas of variation that may benefit from further quantitative research. Methods: A Web-based survey targeted at NET health care providers in Australia, New Zealand, Canada, and the USA was developed by a steering committee of medical oncologists and a research methodologist. Thirty-seven questions elicited information regarding adherence to guidelines, the influence of risk factors on follow-up, and the frequency and choice of modality in follow-up. Results: There were 163 respondents: 59 from Australia, 25 from New Zealand, 46 from Canada, and 33 from the USA (50% medical oncology, 23% surgery, 13% nuclear medicine, and 15% other). Thirty-eight percent of the respondents were “very familiar” with the NCCN NET guidelines, 33% with the ENETS guidelines, and 17% with the ESMO guidelines; however, only 15, 27, and 10%, respectively, found them “very useful”; 63% reported not using guidelines at their institution. The commonest investigations used were CT scans (66%) and chromogranin A (86%). The US respondents were more likely to follow patients up past 5 years, and the Australian respondents utilized more functional and less cross-sectional imaging. When poor prognostic factors were introduced, the respondents recommended more visits and tests. Conclusions: This large international survey highlights variation in current follow-up practices not well addressed by the current guidelines. More quantitative research is required to inform the development of evidence-based guidelines tailored to the pattern of recurrence in NETs.

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Section: Discussionmentioning

confidence: 99%

Follow-Up for Resected Gastroenteropancreatic Neuroendocrine Tumours: A Practice Survey of the Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) and the North American Neuroendocrine Tumor Society (NANETS)

et al. 2018

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“…CgA concentration is higher with PPI usage compared with the alternative class of acid suppressive agents, the histamine type 2 receptor antagonists (H 2 RA), given the more potent gastrin elevating capacity of the former group (49). As predicted, higher CgA levels are noted after long-term treatment (1-8 years) compared with mid-term (!1 year) or short (weekly/ intermittent) treatment, reflecting the effect of sustained gastrin levels in increasing the proliferation of fundic ECL cells and may also cause G-cell hyperplasia (50,51). In these circumstances, apart from elevated CgA, precursor neuroendocrine lesions of the fundus have been considered as a potential hazardous consequence of acid suppression (52).…”

Section: Discussionmentioning

confidence: 99%

A PCR blood test outperforms chromogranin A in carcinoid detection and is unaffected by proton pump inhibitors

Modlin

Aslanian

Bodei

et al. 2014

Endocrine Connections

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A critical requirement in neuroendocrine tumor (NET) management is a blood biomarker test that is sensitive, specific and reproducible. We evaluated a PCR-based 51-transcript signature to detect tumors, compared it with chromogranin A (CgA) and examined the confounding effect of proton pump inhibitors (PPIs), which cause falsely elevated CgA levels. The multigene signature was evaluated in two groups. Group 1: 125 prospectively collected NETs: gastroenteropancreatic NETs (nZ91, including 42 pancreatic and 40 small intestinal), carcinoids of unknown primary (nZ18) and other sites (nZ16). Group 2: prospectively collected non-NET patients receiving PPIs (O1 month; dyspepsia, nZ19; GERD, nZ6; and pancreatitis, nZ4) and 50 controls. All samples were analyzed by PCR (marker genes) and ELISA (DAKO-CgA). Sensitivity comparisons included c ). Significant differences (P!0.001) were noted between pancreas: PCR 95% vs CgA 29.2% (P!10 K9 ) and small intestine: 100 vs 58% (P!10 K4). The multigene test was elevated in all grades (G1-G3), in both local and disseminated disease, and was not normalized by somatostatin analog therapy. It was also elevated in 97% of CgA normal NETs. Group 2: PPI administration increased CgA in 83% and CgA was elevated in 26% of controls. PCR values were not elevated in either group. PCR performance metrics were as follows: sensitivity 98.4%, specificity 100%, positive predictive value 100%, negative predictive value 97.8%, and the ROC-derived area under the curve (AUC) was 0.997. These were significantly better than CgA (all metrics !60%; AUC, 0.54; Z-statistic, 10.44, P!0.0001). A 51-panel multigene blood transcript analysis is significantly more sensitive than plasma CgA for NET detection and is unaffected by acid suppression therapy.

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“…Lack of gastric acid leads to hypergastrinaemia due to loss of negative feedback for gastrin, and this chronic elevation of gastrin levels provoke hyperplasia of the neuroendocrine cells of the stomach, which are able to secrete CgA (32). Proton pump inhibitor (PPI) therapy may increase CgA concentration just five days after first intake, so this drug should be discontinued at least 14 days before the test (33), and possibly 3 weeks is the safest. However, this should always be considered in the context of patients with a high likelihood of a gastrinoma in which case such omission of therapy may be life-threatening.…”

Section: Diagnosis: Proposed Algorithmmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Flushing: current concepts

Huguet

Grossman

2017

European Journal of Endocrinology

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Objective: Flushing can be defined as a sensation of warmth accompanied by erythema that most commonly is seen on the face and which occurs in episodic attacks. Such a problem can be clinically problematic, since many conditions and drugs can be related to flushing, and while often there appears to be no underlying organic disease, it is important to exclude disorders since they may be life-threatening conditions. Design and methods: We performed a search in MEDLINE using the terms 'flushing' in combination with 'carcinoid syndrome', 'pheochromocytoma', 'mastocytosis', 'menopausal hot flush' and 'treatment'. European and American guidelines relating to neuroendocrine tumours, mastocytosis and menopause were reviewed. Results: In this review, we discuss the main causes of flushing and propose an algorithm based on pathogenesis, which can be used to guide the clinical evaluation process. We also review recent significant developments in the assessment and treatment of the carcinoid syndrome and menopausal hot flushes, which should guide the clinical practice regarding this common but sometimes confusing condition. Conclusions: When evaluating flushing, a precise systematic approach is needed to exclude potentially serious underlying causes, although despite this, the cause of the disorder is not always found. If symptoms are not progressive, the patient should be advised about its apparently benign nature in order to avoid unnecessary studies or initiating treatments of minimal benefit.

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

Cited by 51 publications

References 13 publications

Follow-Up for Resected Gastroenteropancreatic Neuroendocrine Tumours: A Practice Survey of the Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) and the North American Neuroendocrine Tumor Society (NANETS)

Follow-Up for Resected Gastroenteropancreatic Neuroendocrine Tumours: A Practice Survey of the Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) and the North American Neuroendocrine Tumor Society (NANETS)

A PCR blood test outperforms chromogranin A in carcinoid detection and is unaffected by proton pump inhibitors

MANAGEMENT OF ENDOCRINE DISEASE: Flushing: current concepts

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