Increased Calcium Ion Levels Following Systemic Circulation After the Selective Arterial Calcium Injection Test

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To the Editor:
Selective arterial calcium injection (SACI) test is performed for the insulinoma localization to provide further localization data before surgery.1 Here, we present a case that showed a false-positive result in the SACI test to localize an insulinoma. We detected the increased calcium ion concentration after systemic circulation after calcium gluconate injection, and the circulating calcium may have stimulated insulin secretion from the insulinoma.
A 67-year-old man was admitted for evaluation after loss of consciousness. On physical examination, he was 167 cm tall and weighed 71.1 kg, with a body weight gain of 10 kg over 10 years. His fasting blood glucose levels were 25 to 75 mg/dL during his hospitalization. Fasting serum insulin and C-peptide levels were 6.1 to 8.0 μU/mL and 1.7 to 2.3 ng/mL, respectively. On the basis of the endocrinological findings, the patient was suspected of having an insulinoma. A computed tomography scan showed a 15-mm-diameter and well-contrasted tumor in the head of the pancreas. Endoscopic ultrasound indicated that the tumor was a pancreatic endocrine tumor. Neither investigation demonstrated any evidence of multiple tumors. We performed arteriography and the SACI test to confirm the localization of the tumor (Fig. 1A, B). A tumor stain was found on superior mesenteric arteriography, and right hepatic artery was found to originate from the superior mesenteric artery (Fig. 1B). We applied calcium gluconate (0.025 mEq Ca2+/kg body weight) for stimulation of the insulinoma as first reported by Doppman et al.1 As shown in Figure 1C, the insulin levels were significantly increased by calcium ion stimulation from all injected arteries.
We considered the reasons why insulin increased after stimulation provided via any artery in the SACI test. Although insulinomas can occasionally have multiple lesions in the pancreas and metastatic lesions in the liver, there was no radiological evidence likely to suggest pseudopositive results. Remarkably, the length of time for the increase in insulin levels after stimulation from the superior mesenteric artery and inferior pancreaticoduodenal artery was shorter than that after stimulation from other arteries (Fig. 1C). Taken together, it was hypothesized that the injected calcium ions might stimulate insulin secretion from the tumor after systemic circulation.
To clarify this hypothesis, with the consent of the patient, the SACI test was performed again as follows. First, 2 catheters were positioned at each of the right hepatic artery and superior mesenteric artery (Fig. 1B). Second, we injected calcium gluconate (0.025 mEq Ca2+/kg body weight) over 4 seconds in the right hepatic artery, and the calcium ion concentrations were measured at the superior mesenteric artery before and after the stimulation. Interestingly, we found an increase in the calcium concentration in the superior mesenteric artery (before: 1.17 mmol/L; 30 s after injection: 1.50 mmol/L; 60 s after injection: 1.35 mmol/L). Consequently, it may have stimulated insulin secretion from the insulinoma. The length of time for systemic circulation was estimated to be 10 to 60 seconds depending on the distance from the injected site. Considering the distance from the right hepatic artery to the superior mesenteric artery, the length of time would be relatively shorter than the general length of the systemic circulation.
Next, we investigated the administration methods of calcium gluconate, which did not cause an increase after systemic circulation. Fick introduced a law describing the diffusion of chemical species in aqueous solutions in 1855.2 According to Fick’s law, the final concentration of chemical species after diffusion is calculated by the diffusion coefficient, initial concentration, time length, unit area, etc. Among these factors, diffusion coefficient, time length, and unit area, which represent the blood vessel, were invariable factors in this patient.
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