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Background: Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection. It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores. Aim: To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger–Ellison syndrome (ZES) treated long-term with gastric antisecretory drugs. Methods: One hundred and nine patients with ZES but without previous gastric resections were studied. All patients underwent assessment of acid control on antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/transferrin ratio). Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters. Results: Eighty-nine patients were taking omeprazole, nine patients were taking histamine H2-antagonists and 11 patients were taking no drugs following curative resection. The mean duration of omeprazole treatment was 5.7 years (range 0.7–12.5 years) and total duration of any treatment was 10.1 years (range 0.7–21 years). Acid hyposecretion was present by at least one criterion in 45% of patients. There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency. Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency. Conclusions: Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B12 in such patients is needed, such monitoring for iron parameters is not necessary.

OBJECTIVE: There is almost no information on the management of patients with functional pancreatic endocrine tumors such as Zollinger-Ellison syndrome during pregnancy. The purpose of this study was to develop an approach for the management of such cases during pregnancy on the basis of experience with five recent cases. STUDY DESIGN: Five women with Zollinger-Ellison syndrome who had seven pregnancies were the subject of this study. Each patient had an initial evaluation to confirm the diagnosis and to establish gastrinoma location and for the presence or absence of multiple endocrine neoplasia type I. In patients with Zollinger-Ellison syndrome diagnosed before conception, various medical or surgical treatments were established before conception and were used to control acid secretion throughout the pregnancy. The presence of upper gastrointestinal symptoms during pregnancy, maternal and fetal complications, gender, and weight of the infant were determined in all cases. Acid control was determined in four of the five patients during six pregnancies. RESULTS: The interval between the onset of Zollinger-Ellison syndrome and the subsequent pregnancy varied from 0.6 to 9.9 years (mean 6.9 ± 1.7 years). Zollinger-Ellison syndrome was unrecognized before pregnancy in two patients (40%); it was diagnosed between 0.2 and 2.4 years after the pregnancy. In three patients the time of diagnosis varied from 2.6 to 9 years before pregnancy. All patients had symptoms from gastric hypersecretion and elevated fasting serum gastrin levels that varied from 20% above normal to 37-fold above normal with mean of 2536 pg/ml (range 124 to 6970 pg/ml). Four of the five patients (80%) had positive secretin and calcium provocative tests. Two patients had multiple endocrine neoplasia type I. The five patients had seven pregnancies. Acid secretion was treated during pregnancy with antacids only (one patient), ranitidine alone (one patient), prior curative gastrinoma resection (one patient, two pregnancies), prior parietal cell vagotomy with incomplete tumor resection (one patient, two pregnancies), and prior parathyroidectomy and use of ranitidine in a patient with multiple endocrine neoplasia type I. In five pregnancies in three of the cases, no gastric antisecretory medications were needed during pregnancy. The mean acid secretion during pregnancy was 11.9 mEq/hr (range 0 to 42 mEq/hr). In the two cases with poor acid control and unrecognized Zollinger-Ellison syndrome mild fetal complications occurred. CONCLUSIONS: It is possible for patients with Zollinger-Ellison syndrome to have pregnancies that are not complicated by gastric acid hypersecretion. If the Zollinger-Ellison syndrome is diagnosed before pregnancy, curative resection or resection with parietal cell vagotomy may obviate the need for gastric antisecretory drugs. If metastases are present or the diagnosis of Zollinger-Ellison syndrome is made after conception, ranitidine in the lowest possible dose should be used to control acid secretion. If acid secretion in uncontrolled, the dose may be increased or omeprazole may be used. (Am J Obstet Gynecol 1997;176:224-33.)

There are six major steps in the management of patients with neuroendocrine tumors (NETs) (carcinoids and pancreatic endocrine tumors). One of the steps that is increasing in its importance is the need to assess primary tumor location and tumor extent in these patients. Without such information, it is not possible to adequately manage these patients. Conventional imaging studies (CT scan, MRI, ultrasound, angiography), functional localization studies measuring hormonal gradients, endoscopic ultrasound, and most recently, somatostatin receptor scintigraphy (SRS) with [125I-DTPA-DPhe1]-octreotide have all been advocated to localize NETs in different studies. Whereas it is now established that for all NETs, except insulinomas, SRS has the greatest sensitivity, it remains unclear whether this increased sensitivity translates into increased clinical usefulness. It, therefore, remains unclear based on fiscal and clinical considerations what should be the recommended algorithm for the use of the different localization methods. To address this issue, we have recently performed two prospective studies on patients with gastrinomas. In this paper, the methods and results of each are summarized and based on these results, an algorithm for localization studies in NETs is proposed. One study assessed the role of SRS in management in 122 patients and shows that the use of SRS changed management in 47 percent of patients according to six different criteria when the patients were stratified according to their principal management problem. Determining whether liver metastases were present is one of the major goals of tumor localization studies and is frequently a source of confusion because of the difficulty in distinguishing small NETs liver metastases from hemangiomas. In the second study, the ability of SRS and other tumor localization methods to distinguish these two possibilities was assessed in 15 patients with small hemangiomas and 15 patients with small hepatic metastases (mean size 1.3 cm). SRS correctly identified 93 percent of the patients with liver metastases and was not positive in any patient with a hemangioma, suggesting it was not a liver metastases. SRS had greater negative and positive predictive value than conventional studies. Based on these two studies, and SRS's greater sensitivity and fiscal considerations, it is proposed that SRS should be the initial tumor imaging study in all NETs except insulinomas, and algorithms for the use of other localization studies in both NETs and insulinomas are proposed. Images Figure 2 Figure 3 Figure 5

Gastric acid secretion is important for absorption of dietary non-haem iron, and iron deficiency is common in gastric hyposecretory states such as after gastric resection. It is not known if prolonged, continuous treatment with potent acid suppressants such as omeprazole will lead to iron deficiency or lower body iron stores.To assess iron stores and the occurrence of iron deficiency anaemia in patients with Zollinger-Ellison syndrome (ZES) treated long-term with gastric antisecretory drugs.One hundred and nine patients with ZES but without previous gastric resections were studied. All patients underwent assessment of acid control on antisecretory agents, determination of tumour extent, evaluation of haematological parameters (Hct, haemoglobin, WBC, MCV, MCHC), and determination of serum iron parameters (iron, ferritin, transferrin, iron/ transferrin ratio). Acid control values for the last 4 years were reviewed, the presence or absence of acid hyposecretion determined using three different criteria and this result correlated with haematological and iron parameters.Eighty-nine patients were taking omeprazole, nine patients were taking histamine H2-antagonists and 11 patients were taking no drugs following curative resection. The mean duration of omeprazole treatment was 5.7 years (range 0.7-12.5 years) and total duration of any treatment was 10.1 years (range 0.7-21 years). Acid hyposecretion was present by at least one criterion in 45% of patients. There were no significant differences between patients with or without acid hyposecretion, taking or not taking omeprazole, having different durations of omeprazole treatment or different durations of total time receiving any antisecretory treatment, for any serum iron parameter, haematological parameter, or for the frequency of iron deficiency. Males and females did not differ in percentage with low ferritin levels or percentage with iron deficiency.Continuous treatment with omeprazole for 6 years or continuous treatment with any gastric antisecretory drug for 10 years does not cause decreased body iron stores or iron deficiency. These results suggest that, in contrast to recent results which show yearly monitoring of vitamin B12 in such patients is needed, such monitoring for iron parameters is not necessary.

Insulinlike growth factor I is a potent mitogen with insulinlike metabolic effects. Insulinlike growth factor I is synthesized in the liver, intestine, and other organs. Insulinlike growth factor I receptors are widely distributed and structurally similar to insulin receptors. Frozen sections of rabbit gastrointestinal tract were incubated in buffer containing 40 pmol/L [125I]insulinlike growth factor I. Binding was saturable, temperature- and time-dependent, and reversible. Saturation binding experiments showed a single class of high-affinity receptors (Kd = 0.9 nmol/L, Bmax = 0.36 pmol/mg protein). The IC50s for insulinlike growth factor I and insulinlike growth factor II were 3 nmol/L and 90 nmol/L, respectively; whereas insulin at 1-3 mumol/L displaced 50% of specific binding. Autoradiography of insulinlike growth factor I binding demonstrated significant differences in receptor density in gastrointestinal smooth muscle, epithelium of the esophagus, stomach, small intestine, and colon. These results indicate that a single class of specific, high-affinity insulinlike growth factor I receptors were distributed in muscular and mucosal layers of the entire rabbit gastrointestinal tract. Insulinlike growth factor I is likely to be an important local mediator of intestinal growth and metabolism.