Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal



Page Path
HOME > Search
4 "Insulinoma"
Article category
Publication year
Original Article
Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea
Chang-Yun Woo, Ji Yun Jeong, Jung Eun Jang, Jaechan Leem, Chang Hee Jung, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Jung Bok Lee, Ki-Up Lee
Diabetes Metab J. 2015;39(2):126-131.   Published online March 9, 2015
  • 5,591 View
  • 85 Download
  • 23 Web of Science
  • 20 Crossref
AbstractAbstract PDFPubReader   

Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.


To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.


Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.


The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.


Citations to this article as recorded by  
  • Case report: Insulinomatosis: description of four sporadic cases and review of the literature
    Delmar Muniz Lourenço, Maria Lucia Corrêa-Giannella, Sheila Aparecida Coelho Siqueira, Marcia Nery, Flavio Galvão Ribeiro, Elizangela Pereira de Souza Quedas, Manoel de Souza Rocha, Ramon Marcelino do Nascimento, Maria Adelaide Albergaria Pereira
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Use of Translational Science, Continuous Glucose Monitoring in the Primary Care Setting for Management of Nesidioblastosis: A Case Report and Literature Review
    Karuna Manandhar, Othman Farahneh, Ahmad Damlakhy, Ali Lattouf, Gerardo Munoz Monaco
    Cureus.2024;[Epub]     CrossRef
  • Insulin Autoimmune Syndrome: A Systematic Review
    MingXu Lin, YuHua Chen, Jie Ning, Tatsuya Kin
    International Journal of Endocrinology.2023; 2023: 1.     CrossRef
  • Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS): Review of the Literature of a Rare Cause of Hyperinsulinemic Hypoglycemia
    Martin Philipp Dieterle, Ayman Husari, Sophie Nicole Prozmann, Hendrik Wiethoff, Albrecht Stenzinger, Manuel Röhrich, Uwe Pfeiffer, Wolfgang Rüdiger Kießling, Helena Engel, Harald Sourij, Thorsten Steinberg, Pascal Tomakidi, Stefan Kopf, Julia Szendroedi
    Biomedicines.2023; 11(6): 1732.     CrossRef
  • An Uncommon Cause of Recurrent Presyncope, Dizziness, and Tachycardia: A Case Report of Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS)
    Martin Philipp Dieterle, Ayman Husari, Sophie Nicole Prozmann, Hendrik Wiethoff, Albrecht Stenzinger, Manuel Röhrich, Uwe Pfeiffer, Wolfgang Rüdiger Kießling, Helena Engel, Harald Sourij, Thorsten Steinberg, Pascal Tomakidi, Stefan Kopf, Julia Szendroedi
    Biomedicines.2023; 11(6): 1741.     CrossRef
  • An Uncommon Case of Recurrent Hypoglycemic Episodes in a Healthy Non-diabetic Male: Insulin Autoimmune Syndrome
    Kanwarpal K Dhaliwal, Gaurav Bector, Saurabh Arora, Amanpreet Singh, Sanjay Kalra
    Cureus.2023;[Epub]     CrossRef
  • The After-Dinner Dip
    Caren G. Solomon, Gertrud L.G. Haverkamp, Richard G. Ijzerman, Jos Kooter, Yvonne H.M. Krul-Poel
    New England Journal of Medicine.2022; 386(22): 2130.     CrossRef
  • Hirata's disease (insulin autoimmune syndrome) following envenomation by a common krait
    Subramanian Senthilkumaran, Stephen W. Miller, Harry F. Williams, Ponniah Thirumalaikolundusubramanian, Sakthivel Vaiyapuri, Ketan Patel
    Toxicon.2022; 219: 106923.     CrossRef
  • Analysis of the clinical characteristics of insulin autoimmune syndrome induced by methimazole
    Linli Sun, Weijin Fang, Dan Yi, Wei Sun, Chunjiang Wang
    Journal of Clinical Pharmacy and Therapeutics.2021; 46(2): 470.     CrossRef
  • Continuous glucose monitoring and Rituximab treatment in insulin autoimmune syndrome
    Hiya Boro, Uttio Gupta, Charandeep Singh, Rakhi Malhotra, Rajesh Khadgawat
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2021; 15(6): 102294.     CrossRef
  • Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description

    Daniele Cappellani, Enrico Macchia, Alberto Falorni, Piero Marchetti
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 963.     CrossRef
  • Nationwide survey of endogenous hyperinsulinemic hypoglycemia in Japan (2017–2018): Congenital hyperinsulinism, insulinoma, non‐insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata’s disease)
    Yuki Yamada, Kana Kitayama, Maki Oyachi, Shinji Higuchi, Rie Kawakita, Yutaka Kanamori, Tohru Yorifuji
    Journal of Diabetes Investigation.2020; 11(3): 554.     CrossRef
  • Insulin Autoimmune Syndrome – A Case Series
    Hiya Boro, Uttio Gupta, Charandeep Singh, Rakhi Malhotra, Rajesh Khadgawat
    European Endocrinology.2020; 16(2): 168.     CrossRef
  • Management of Insulin Autoimmune Hypoglycaemia: Single‐centre experience from Western India with systematic review of world literature
    Muniraj Patel, Ravikumar Shah, Swati Ramteke‐Jadhav, Virendra Patil, Shivendra Kumar Patel, Anurag Lila, Nalini Shah, Tushar Bandgar
    Clinical Endocrinology.2020; 92(5): 409.     CrossRef
  • Is insulin intoxication still the perfect crime? Analysis and interpretation of postmortem insulin: review and perspectives in forensic toxicology
    Charline Bottinelli, Nathalie Cartiser, Fabien Bévalot, Laurent Fanton, Jérôme Guitton
    Critical Reviews in Toxicology.2020; 50(4): 324.     CrossRef
  • Insulin autoimmune syndrome induced by exogenous insulin injection: a four-case series
    Yimin Shen, Xiaoxiao Song, Yuezhong Ren
    BMC Endocrine Disorders.2019;[Epub]     CrossRef
  • An observational analysis of insulinoma from a single institution
    S Shao, Z Zeng, S Hu
    QJM: An International Journal of Medicine.2018; 111(4): 237.     CrossRef
  • Anti-tuberculosis Treatment-Induced Insulin Autoimmune Syndrome
    Jung Suk Han, Han Ju Moon, Jin Seo Kim, Hong Il Kim, Cheol Hyeon Kim, Min Joo Kim
    The Ewha Medical Journal.2016; 39(4): 122.     CrossRef
  • Spontaneous hypoglycemia: diagnostic evaluation and management
    Leelavathy Kandaswamy, Rajeev Raghavan, Joseph M. Pappachan
    Endocrine.2016; 53(1): 47.     CrossRef
  • Hypoglycemia due to Insulin Autoimmune Syndrome: A rare cause not to be forgotten
    Sarah Alam, Maaz Ozair, Jamal Ahmad
    Journal of Clinical and Translational Endocrinology: Case Reports.2016; 2: 7.     CrossRef
Case Reports
A Case of Insulinoma Associated with Type 2 Diabetes Mellitus.
Sung Soo Yoo, Wan Sub Shim, Chul Hyun Kim, Ki Cheol Ha, Seung Min Lye, Eun Joo Kim, So Hun Kim, Seong Bin Hong, Moonsuk Nam, Yong Seong Kim
Korean Diabetes J. 2007;31(6):517-519.   Published online November 1, 2007
  • 2,119 View
  • 23 Download
AbstractAbstract PDF
An insulinoma is an endocrine tumor of the pancreas derived from the beta cells with abnormal insulin secretion. An insulinoma is rare, the incidence being estimated at only four per one million person-years. The association of diabetes mellitus and insulinoma is extraordinarily rare, but we should not overlook an insulinoma as a possible cause of hypoglycemia in patients with diabetes mellitus. A 70-year-old diabetic man who had been treated with oral hypoglycemic agents for type 2 diabetes suffered from night sweating for 10 days. Even after he stopped taking his oral hypoglycemic agents, the night sweating continued. The patient was admitted to evaluate the cause of the recurrent hypoglycemic events. After a 72-hour fasting test and selective arterial calcium stimulation test with venous sampling, he was diagnosed with insulinoma accompanied by type 2 diabetes mellitus. In the course of the study, the patient was also incidentally diagnosed with lung cancer.
A Case of Primary Insulin Autoimmune Syndrome in a Patient Suspected of Having an Insulinoma.
Sung Ju Lee, Jee Hyun Kong, Joo Young Nam, Jong Suk Park, Chul Sik Kim, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee
Korean Diabetes J. 2004;28(1):45-50.   Published online February 1, 2004
  • 1,005 View
  • 17 Download
AbstractAbstract PDF
Insulin autoimmune syndrome consists of fasting hypoglycemia, hyperinsulinemia and detectable insulin-binding antibodies in patients never been exposed to exogenous insulin. Most affected patients present with other autoimmune disorders, most often Graves' disease. A significant increase in the insulin and C-peptide plasma concentrations and the presence of other anti organ antibodies are also observed. Awareness of insulin autoimmune syndrome hypoglycemia is important as this may produce severe neuroglycopenic symptoms, which may be confused with the presence of an insulinoma. The correct diagnosis is important to avoid unnecessary surgical intervention in patients who are best treated with conservative support, watchful waiting, or in some cases, immunosuppressive therapy. Herein, a case of autoimmune insulin syndrome, suspected as being an insulinoma is reported.
Original Article
Measurement of Anti-38kD Antibody in Korean patients with Insulin-Dependent Diabetes Mellitus by Western Blot Analysis.
Sun Ja Kwon, Hong Kyu Lee, Hyeon Kyu Kim
Korean Diabetes J. 1998;22(2):135-144.   Published online January 1, 2001
  • 821 View
  • 19 Download
AbstractAbstract PDF
Insulin-dependent diabetes mellitus (IDDM) is characterized by the destruction of pancreatic b-cells, which is associated with the genetic susceptibility and the production of antibodies to a numter of islet cell antigens(ICA). A possible target antigen, 38kD antigen, was suggested by the proliferation of CD4 T cells frorn a newly diagnosed patient in response to a 38kD polypeptide of the insulin-secretory-granule membrane. Autoantibody to a rat islet cell -protein of 38kD was detectable in the sera of diabetes-prone biobreeding rats by both immunoprecipitation and differential Westem blot analysis. Anti-38kD antibodies were also found to have a 76% sensitivity at the time of diagnosis in diabetic children by immunoprecipitation. In the Asian populations, it has been reported that clinical and immunologic characteristics of IDDM are quite different from those of Caucasians, say low prevalence of ICA. In Korean, there has never been reported the presence of the anti-38kD antibody. Moreover, the time-consuming and laborious nature of assay, such as T-cell proliferation and immuno-precipitation, makes it difficult to use for large population screenings. In the present study, we aimed to evaluate the prevalence of anti-38kD antibody as a immunologic marker in Korean IDDM patients by Western blot analysis. METHODS: Anti-38kD antibody was detected by Western blot analysis using the lysate of rat insulinoma cell line(RINmSF) as an antigenic source. ICA was determined by enzymatic immunohistochemical analysis. The prevalence of anti-38kD antibody and ICA was measured in 38 cases of IDDM, whose mean age at diagnosis and mean duration of IDDM were 25.2+14.2 years and 0.66+0.97 years, respectively. RESULTS: Using Western blot analysis with the lysate fraction of RIN cell, the prevalence of anti-38kD autoantibody(21.1%) in the IDDM paients was significantly higher than that in the control subjects(0.0%, P<0.05). Clinical characteristics between anti-38kD antibody-positive and -negative IDDM patients were not different. In immunohisto-chemical staining, ICA was detected in 18.2% of the IDDM patients, but not in the control subjects. The prevalence of anti-38kD antibody was 21.7%, 28.6% and 12.5% in the patients of less 1 year, 1 year and 2~4 years, respectively, showing no statistically significant difference in the prevalence according to the duration of IDDM. As previously reported, however, the prevalence of ICA decreased with increasing duration of IDDM. CONCLUSION: These results suggested that the anti-38kD autoantibody is a candidate of autoantibodies for the immunologic markers of Korean IDDM We expect the development of the more methods for the detection of anti-38kD in the future.

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer