Hormonal changes revealed by selective arterial calcium injection tests in patients with insulinoma treated with EUS–guided ethanol injection

EUS–guided ethanol injection (EUS-EI) has recently been proposed as a therapeutic option for patients with functional pancreatic neuroendocrine neoplasms (PNENs), and some reports have described the improvement of patients' hormone-related symptoms after treatment.[1–4] However, few studies have conducted a detailed hormonal evaluation after treatment.[1,2] The selective arterial calcium injection (SACI) test is a useful method for evaluating changes in hormonal dynamics in patients with functional PNENs.[5] We herein report the first case of insulinoma in which SACI tests could be performed before and after EUS-EI. A 78-year-old man with hypoglycemia was referred to our hospital for a further examination and treatment. Nonsymptomatic hypoglycemia at night and early in the morning was repeatedly detected using flash glucose monitoring. A 72-hour fasting test revealed hypoglycemia (42 mg/dL) within 10.5 hours in the presence of inappropriate elevated serum insulin level of 9.7 μU/mL and C-peptide level of 2.54 ng/mL. Abdominal contrast-enhanced computed tomography (CE-CT) showed a 1-cm enhancing tumor in the pancreatic head [Figure 1]. In the SACI test, calcium infusion into the gastroduodenal artery (GDA) led to a remarkable increase in venous insulin levels, whereas stimulation of other arteries, including the hepatic artery, did not induce insulin overproduction, suggesting that the pancreatic head lesion was an insulin-producing tumor [Figure 2A]. An EUS-guided biopsy confirmed the tumor to be a PNEN with grade 1 histology. Considering the patient's age and surgical invasion of the pancreaticoduodenectomy, we decided not to surgically remove the tumor, performing EUS-EI instead. A 25-gauge needle was advanced into the tumor, and 1.25 mL pure ethanol was injected until the hyperechoic blush extended to the tumor's entire margin [Figure 3]. No procedure-related complications occurred. Three days after treatment, disappearance of tumor enhancement on CE-CT was confirmed [Figure 4]. In addition, a reevaluation of the SACI test showed markedly reduced insulin elevation induced by calcium infusion compared with the preoperative evaluation [Figure 2B]. No tumor recurrence on CE-CT and no hypoglycemic events were reported over 3 years of follow-up [Figure 5]. The SACI test after treatment is useful for evaluating efficacy against functional PNENs.Figure 1: Contrast-enhanced computed tomography (CE-CT) images before treatment. (A) A 1.0-cm hypervascular tumor in the pancreas head (arrow). (B) Coronal image.Figure 2: The selective arterial calcium injection (SACI) test. Calcium gluconate (0.025 mEq/kg) was injected into each artery (SMA, pSPA, dSPA, GDA, RHA, and LHA) for 30 seconds, and venous blood samples were collected from the right hepatic vein at specified intervals (pre, 30, 60, 90, and 120 seconds). Each calcium infusion was performed at least 5 minutes apart. (A) Venous insulin levels after calcium injection into the GDA significantly increased, suggesting that the lesion in the pancreatic head was an insulin-producing tumor. (B) After treatment, the pathological insulin elevation induced by calcium infusion into the GDA declined remarkably. SMA, superior mesenteric artery; pSPA, proximal splenic artery; dSPA, distal splenic artery; GDA, gastroduodenal artery; RHA, right hepatic artery; LHA, left hepatic artery.Figure 3: EUS–guided ethanol injection images. (A) Before the treatment: a hypoechoic tumor in the head of the pancreas. (B) Immediately after the EUS-guided ethanol injection, 1.25 mL of pure ethanol was injected. (C) After the EUS-guided ethanol injection, the hyperechoic blush extended to the tumor's entire margin. *Main pancreatic duct.Figure 4: Contrast-enhanced computed tomography (CE-CT) images after the treatment. (A) Three days after the treatment: appearance of a low-density area without contrast enhancement (arrow). (B) Coronal image.Figure 5: Follow-up images after the treatment. (A) Contrast-enhanced computed tomography (CE-CT) at 3 years after treatment: disappearance of contrast enhancement of the tumor in the pancreas head (circle). (B) EUS image at 1½ years after treatment: there was no low-echoic mass at the previous tumor site (circle). *Main pancreatic duct. SMV: superior mesenteric vein.