Nutrient Malabsorption in the Zollinger-Ellison Syndrome

King, Charles; Toskes, Phillip P.

doi:10.1001/archinte.1983.00350020175033

Cited by 12 publications

(1 citation statement)

References 13 publications

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“…In general, ZES patients will not be a good model to study this association, even though they have life-time treatment with PPIs, frequently with higher PPI doses, for a number of reasons, which will overall confound the determination of present/cause of bone changes/osteoporosis or bone fracture. First, the delay in diagnosis for ZES patients is 6–7 years [29,116] and during this time, diarrhea frequently develops and may be associated with malabsorption [21,29,149,300,349]. This malabsorption can affect mineral/calcium absorption also so that these patients may develop an additional cause independent of any anti-secretory drug for bone changes/fractures [350].…”

Section: Insights Of Effects Of Chronic Hypergastrinemia In Patienmentioning

confidence: 99%

Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger–Ellison Syndrome

Lee

Ramos-Álvarez

Ito

et al. 2019

IJMS

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The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25–70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10–20 years). Zollinger–Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.

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