Endoscopic ultrasound localization of a solitary insulinoma of pancreatic tail misdiagnosed as epilepsy: case report

Abdom Imaging 28:859 – 861 (2003) DOI: 10.1007/s00261-003-0039-5

Abdominal Imaging © Springer-Verlag New York Inc. 2003

Endoscopic ultrasound localization of a solitary insulinoma of pancreatic tail misdiagnosed as epilepsy: case report N. Muscatiello,1 R. Cuomo,2 M. Gentile,3 V. De Francesco,1 V. Stoppino,1 A. Contillo,4 A. Salcuni,4 C. Natale,5 C. Panella,3 E. Ierardi3 1

Gastroenterology Unit, “Ospedali Riuniti” of Foggia, Viale L. Pinto, 71100 Foggia, Italy Hepatogastroenterology Unit, Department of Experimental Medicine, University of Napoli, Via S. Pansini, 5-80131 Naples, Italy 3 Department of Gastroenterology, University of Foggia, c/o Ospedali Riuniti, Viale L. Pinto, 71100 Foggia, Italy 4 General Medicine Unit, “Ospedali Riuniti” of Foggia, Viale L. Pinto, 71100 Foggia, Italy 5 General Surgery Unit, “Ospedali Riuniti” of Foggia, Viale L. Pinto, 71100 Foggia, Italy 2

Received: 2 January 2003/Accepted: 22 January 2003

Abstract A 17-year-old female patient with features of epilepsy was treated with valproic acid. Two years later, hypoglycemia and hyperinsulinemia appeared. Transabdominal ultrasonography, spiral computed tomography, and indium-111 Octreoscan were performed without positive results. Endoscopic ultrasonography identified an oval tumor in the pancreatic tail with a color Doppler hypervascular pattern. Surgical enucleation decreased levels of insulin and C-peptide within 20 min, and the patient became free of symptoms and medications. Key words: Endoscopic ultrasonography—Insulinoma— Epilepsy—Pancreatic tumors—C-peptide.

Insulinomas are rare neoplasms, with a prevalence of one in 1.25 million [1]. These tumors often are clinically demonstrated by the occurrence of neuroglycopenic symptoms characterized by seizure recurrence, which may be misinterpreted as epilepsy even on the bases of electroencephalographic and radiologic features [2]. Moreover, misdiagnosis delays treatment, with the likelihood a permanent neurologic deficit [3]. Insulinomas are often small (⬃1 cm), solitary, and confined to the pancreas. These peculiarities account for the frequent difficulties in localizing these tumors by current noninvasive imaging techniques such as transabdominal ultrasonography, computed tomography, and nuclear scanning [4]. For these reasons, localization has Correspondence to: E. Ierardi

often been performed intraoperatively by palpation or ultrasonography in the course of surgical operations [5, 6]. Nevertheless, preoperative detection of the tumor site offers the undoubted advantages of shortening surgery time and avoiding unnecessary pancreatic resections and the occurrence of postsurgical complications such as pancreatic fistulae. Preliminary reports have shown promising results for endoscopic ultrasonography (EUS) in the accurate preoperative localization of insulinomas [7, 8]. On this basis, we believe it is of relevance to report the case of a patient with epilepsy in whom EUS revealed an insulinoma of the pancreatic tail with consequent complete resolution of the disease by surgery.

Case report A 17-year-old female patient (weight, 74 kg; height, 159 cm) was referred for evaluation of recurrent seizures. Her clinical history revealed a diagnosis of epilepsy based on the clinical (weakness, dizziness, and confused behavior) and electroencephalographic (diffuse theta waves and sharp elements after hyperpnea) features. The patient had been treated with valproic acid at the dose of 1 g/day for 2 years. After the last seizure episode, marked hypoglycemia was observed in both basal conditions (22 mg/dL) and during a formal fast (33 mg/dL). The patient described a sense of detachment and appeared mildly confused. Signs and symptoms promptly reversed after intravenous glucose administration. The immunoreactive insulin level was 29 ␮U/mL (normal ⬍ 22 ␮U/mL), and the C-peptide

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N. Muscatiello et al.: Insulinoma and epilepsy

Fig. 1. EUS demonstrates an oval lesion in the pancreatic tail, with a maximal diameter of 14 mm (A) and a hypervascular pattern on color Doppler (B) (depicted in gray-scale).

Fig. 2. Insulin (left) and C-peptide (right) levels in portal and peripheral blood before and 20 min after surgical enucleation of the insulinoma.

level was 10.1 ng/mL (normal, 1.1–3.2 ng/mL). All these features were consistent with hyperinsulinism of an endogenous source. Other possible endocrine causes of seizures, such as pheochromocytoma, hyperparathyroidism, primary hyperaldosteronism, and multiple endocrine neoplasia type 1, were excluded by appropriate laboratory and imaging investigations, including serum levels of prolactin, calcium, parathyroid hormone, corticotrophin, cortisol, and aldosterone, and cerebral magnetic resonance imaging and parathyroid ultrasonography. Based on clinical suspicion of insulinoma, transabdominal ultrasonography, spiral computed tomography, and indium-111 Octreoscan were performed without positive results. However, EUS identified an oval tumor with a maximal diameter of 14 mm at the level of the pancreatic tail. Color power Doppler showed a hypervascular pattern in this area (Fig. 1; depicted in gray scale). On this basis, the patient underwent surgical enucleation of the lesion, which induced a dramatic decrease of insulin and C-peptide levels in the portal and peripheral blood within 20 min (Fig. 2). Histologic examination of surgical specimens confirmed the diagnosis of insulinoma

by specific immunohistochemical staining. After surgery, the patient became free of symptoms and medicines during the 12-month follow-up.

Discussion Insulinomas are rare, small, and often benign isolated neoplasms. For these peculiarities, most reports available in the literature concern single cases similar to that we have described in this article. However, the history of our patient emphasizes some interesting aspects concerning clinical presentation, diagnostic modus operandi, and therapeutic resolution. From the clinical point of view, the presence of insulinoma must be always considered in current practice when investing neurologic symptoms mimicking idiopathic epilepsy and acute disorders of cognition, psychosis, transient ischemia, dementia, and choreoathetosis [3]. Misdiagnosis must be avoided to prevent permanent neurologic damage [3] and possibly fatal coma [9]. Therefore, the detection of an inappropriate elevation of serum insulin in the face of hypoglycemia is an oligatory diagnostic step [10]. In the

N. Muscatiello et al.: Insulinoma and epilepsy

presence of these findings, multiple endocrine neoplasia type 1 needs to be excluded because 10% of insulinomas arise in the context of this disorder [11]. Our experience with this patient confirms that EUS has a very favorable diagnostic capacity. Moreover, previous reports have confirmed the EUS finding of insulinoma by visceral angiography with the aim of demonstrating a hypervascular pattern [8]. In our patient, EUS allowed identification of this feature by color power Doppler, thus avoiding further invasive investigations. Portal blood sampling to assay serum glucose and immunoreactive insulin has been shown to represent a useful guide to the completeness of the resection of insulin-producing tumors [12]. This procedure also has been described as a useful intraoperative diagnostic tool in the absence of a demonstration of the lesion by imaging techniques [13]. In our case, we found good correlation between results of portal and peripheral blood samples, the rapid insulin and C-peptide decreases, with the consequent glucose rise as an excellent predictor of the therapeutic success of insulinoma enucleation. In conclusion, this case report confirmed the key role of EUS in the diagnosis of small insulinomas and suggested its diagnostic utility for some patients with neurologic disorders. References 1. Perry PR, Vinik AI. Endocrine tumors of the gastrointestinal tract. Annu Rev Med 1996;47:57– 68

861 2. Hui AC, Ozaki R, Kay R, Cockram CC. Seizure recurrence in temporal lobe epilepsy. Int J Clin Pract 2002;56:63– 64 3. Shaw C, Haas L, Miller D, Delahunt J. A case report of paroxysmal choreoathetosis due to hypoglycemia induced by an insulinoma. J Neurol Neurosurg Psichiatry 1996;61:194 –195 4. Chung MJ, Choi BI, Han JK, et al. Functioning islet cell tumors of the pancreas: localization with dynamic spiral CT. Acta Radiol 1997;38:135–138 5. Grant CS, Van Heerden J, Chaarboneau JW, et al. Insulinoma: the value of intraoperative ultrasonography. Arch Surg 1988;123:843– 848 6. Proye C, Boissel P. Preoperative imaging versus intraoperative localization of tumors in adult surgical patients with hyperinsulinemia: a multicenter study of 338 patients. World J Surg 1988;12: 685– 689 7. Hall RS, Hanley JF, Georgitis W, McNally PR. Endoscopic localization of pancreatic insulinoma: case report and review of the localization techniques. Mil Med 1998;163:853– 856 8. Pitre J, Soubrane O, Palazzo L, Chapuis U. Endoscopic ultrasound ultrasonography for the preoperative localization of insulinomas. Pancreas 1996;13:55– 60 9. Akanji AO, George AO, Olasode BJ, Osotimehin BO. Insulinoma in pregnancy presenting as seizure disorder: a case report. East Afr Med J 1992;69:117–119 10. Service FJ. Hypoglicemic disorders. N Engl J Med 1995;322:1144 – 1152 11. Sheppard BC, Norton JA, Doppman JL, et al. Management of islet cell tumors in patients with multiple endocrine neoplasia: a prospective study. Surgery 1989;106:1108 –1118 12. Pdrazzoli S, Pasquali C, Miotto D, Feltrin GP, Petrin P. Transhepatic portal sampling for pre-operative localization of insulinoma. Surg Gynecol Obstet 1987;185:101–106 13. Kadama T, Ito Y, Obara T, Fujimoto Y, et al. Recently experienced ten cases of insulinoma preoperative diagnosis of localization and intraoperative simultaneous monitoring of glucose and insulin. Nippon Geka Gakkai Zasshi 1988;58:398 – 407