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      Insulinoma case series: Experience of a tertiary care center

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          Abstract

          Background:

          Insulinomas are usually solitary; benign and encapsulated small lesions and majority of them measure <2 cm in diameter. They pose a challenge for pre-operative localization. Definitive treatment is surgical excision of the tumor. Intra-operative ultrasonography (IOUS), transhepatic portal venous sampling (THPVS) and positron emission tomography (PET) scan can be done for tumors not localized by conventional imaging modalities.

          Materials and Methods:

          A retrospective study of patients diagnosed with insulinoma during the period 2004-2012 (8 years) was done. Biochemical diagnostic criteria used were plasma concentrations of glucose <55 mg/dl with corresponding insulin level >3.0 μU/ml (18 pmol/L) and C-peptide of >0.6 ng/ml (0.2 nmol/L). The localization of the tumor was done by various modalities namely computed tomography (CT), magnetic resonance imaging (MRI), IOUS, PET and portal venous sampling. The initial localizing technique in most of these patients were CT or MRI imaging, or both and those who were not localized by the above modalities were subjected to PET CT or THPVS or intra-operative ultrasound depending on the initial imaging results and patient's consent. All the modalities were not used in the same patient, but the modalities were decided as per the imaging results, patient's consent and affordability for the procedure.

          Results:

          Ninteen cases of insulinoma aged between 10 and 66 years, with a median age of 47 years were included in the analysis. There were 10 males and nine females. Eighty-three percent of patients presented with pre-prandial hypoglycemia ( n = 15). Different modalities were employed for pre-operative localization of these patients out of which 5 (26.31%) cases were localized with CT, 5 (26.31) cases with MRI, 5 (26.31%) with THPVS, 1 (5.26%) case with PET CT, 3 (15.78%) of them could not be localized out of which 2 (10.52%) were localized by IOUS and 1 (5.26%) case the lesion could not be localized. Among 19 cases, 12 underwent surgery out of which one patient underwent distal pancreatectomy as tumor was not localized; eight underwent laparoscopic enucleation; three of them required intra-operative exploration and seven of them were not operated, as they did not give consent for surgery. In all the cases, the size of the insulinoma ranged between 1 and 2 cm.

          Conclusion:

          We report our experience with 19 cases of insulinoma and analyze the role of pre- and intra-operative imaging modalities in the surgical management of insulinomas. Most of our cases were symptomatic, and the most common presentation was with pre-prandial hypoglycemia. THPVS, PET scan and intra-operative ultrasound added to diagnostic sensitivity in some cases not localized by CT or MRI.

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          Most cited references26

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          68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT.

          The aim of this study was to evaluate the diagnostic value of a new somatostatin analog, (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ((68)Ga-DOTA-TOC), for PET in patients with known or suspected neuroendocrine tumors. PET was compared with conventional scintigraphy and dedicated CT. Eighty-four patients (48 men, 36 women; age range, 28-79 y; mean age +/- SD, 58.2 +/- 12.2 y) were prospectively studied. For analysis, patients were divided into 3 groups: detection of unknown primary tumor in the presence of clinical or biochemical suspicion of neuroendocrine malignancy (n = 13 patients), initial tumor staging (n = 36 patients), and follow-up after therapy (n = 35 patients). Each patient received 100-150 MBq (68)Ga-DOTA-TOC. Imaging results of PET were compared with (99m)Tc-labeled hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC) and (111)In-DOTA-TOC. CT was also performed on every patient using a multidetector scanner. Each imaging modality was interpreted separately by observers who were unaware of imaging findings before comparison with PET. The gold standard for defining true-positive (TP), true-negative (TN), false-positive (FP), and false-negative (FN) results was based on all available histologic, imaging, and follow-up findings. PET was TP in 69 patients, TN in 12 patients, FP in 1 patient, and FN in 2 patients, indicating a sensitivity of 97%, a specificity of 92%, and an accuracy of 96%. The FP finding was caused by enhanced tracer accumulation in the pancreatic head, and the FN results were obtained in patients with a tumor of the gastrointestinal tract displaying liver metastases. (68)Ga-DOTA-TOC showed higher diagnostic efficacy compared with SPECT (TP in 37 patients, TN in 12 patients, FP in 1 patient, and FN in 34 patients) and diagnostic CT (TP in 41 patients, TN in 12 patients, FP in 5 patients, and FN in 26 patients). This difference was of statistical significance (P < 0.001). However, the combined use of PET and CT showed the highest overall accuracy. (68)Ga-DOTA-TOC PET shows a significantly higher detection rate compared with conventional somatostatin receptor scintigraphy and diagnostic CT with clinical impact in a considerable number of patients.
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            Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study.

            For the 60-year period from 1927 through 1986, we assessed the incidence, recurrence, and long-term survival among all Mayo Clinic patients with histologically confirmed functioning insulinoma. With use of the complete medical record system at Mayo and the comprehensive epidemiologic data base of residents of Olmsted County, Minnesota, we found 224 patients in whom an initial pancreatic exploration at Mayo had confirmed the presence of insulinoma. The median age (and range) of these patients at surgical diagnosis was 47 (8 to 82) years, and 59% were female patients. During the study period, eight cases of insulinoma occurred among residents of Olmsted County; their age and gender distributions were similar to those of the total cohort. The incidence of insulinoma among residents of Olmsted County increased during the study period to a stable level during the last 2 decades of 4 cases per 1 million person-years. For the total cohort, 7.6% had multiple endocrine neoplasia type I (MEN I), and 5.8% had malignant insulinoma. The risk of recurrence was greater among patients with MEN I (21% at 10 and 20 years) than in those without MEN I (5% at 10 years and 7% at 20 years). Although survival of the total cohort was not significantly impaired, it was significantly worse than expected for patients with malignant insulinoma (29% versus 88% expected at 10 years postoperatively). We conclude that insulinoma is less rare than previously suspected. After successful surgical removal, the long-term risk of recurrent insulinoma is relatively high in patients with MEN I; for patients with benign disease, the long-term survival is normal.
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              Insulinoma.

              Although rare, insulinomas are the most common functioning islet cell tumour of the pancreas. Recognition of the key neuroglycopenic symptoms should trigger the initial investigation. Biochemical proof of endogenous hyperinsulinemic hypoglycemia establishes the diagnosis. Several options are available for imaging and localizing these tumours including ultrasonography, computed tomography, and intra-arterial calcium stimulation with venous sampling. The tumours are usually small, single, benign, well-circumscribed, and evenly distributed throughout the pancreas. This tumour may be a part of the multiple endocrine neoplasia type 1 (MEN-1) syndrome, in which case the tumours are almost always multiple. Surgical treatment is the only curative method, traditionally accomplished with enucleation or partial pancreatic resection. Patients are almost invariably cured lifelong with complete excision of a benign insulinoma. The most recent developments in this area are the recognition of noninsulinoma pancreatogenous hypoglycemia syndrome as a cause of organic hypoglycemia, and the development of laparoscopic techniques to excise these tumours.
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                Author and article information

                Journal
                Indian J Endocrinol Metab
                Indian J Endocrinol Metab
                IJEM
                Indian Journal of Endocrinology and Metabolism
                Medknow Publications & Media Pvt Ltd (India )
                2230-8210
                2230-9500
                Nov-Dec 2014
                : 18
                : 6
                : 858-862
                Affiliations
                [1] Department of Endocrinology, M. S. Ramaiah Medical College, Bengaluru, Karnataka, India
                [1 ] Department of Radiology, M. S. Ramaiah Medical College, Bengaluru, Karnataka, India
                [2 ] Kadri Clinic, Bengaluru, Karnataka, India
                [3 ] CDEC, Bengaluru, Karnataka, India
                Author notes
                Corresponding Author: Dr. Pramila Kalra, Department of Endocrinology, M. S. Ramaiah Medical College, Bengaluru, Karnataka, India. E-mail: kalrapramila@ 123456gmail.com
                Article
                IJEM-18-858
                10.4103/2230-8210.141385
                4192995
                f51e51fb-b128-4563-97fa-30e1e9ba5d36
                Copyright: © Indian Journal of Endocrinology and Metabolism

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Brief Communication

                Endocrinology & Diabetes
                hypoglycemia,insulinoma,transhepatic portal venous sampling
                Endocrinology & Diabetes
                hypoglycemia, insulinoma, transhepatic portal venous sampling

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