ICJIM
Intercontinental Journal of Internal Medicine

The Intercontinental Journal of Internal Medicine aims to publish issues related to all fields of internal medicine of the highest scientific and clinical value at an international level and accepts articles on these topics.

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Non-diabetic hypoglycemia
Abstract
Glucose is the main substrate utilized by the brain, and therefore numerous counterregulatory mechanisms exist to maintain plasma glucose concentration. This makes it rare for hypoglycemia to develop in people who are not taking hypoglycemic drugs, such as insulin or sulfonylureas, for diabetes. The symptoms of hypoglycemia are nonspecific. The presence of Whipple’s triad is necessary for diagnosis. When symptoms occur spontaneously, the patient can be evaluated for hypoglycemia. If this is not possible, then a 72-hour fasting test or a mixed meal tolerance test can be performed to create conditions for symptoms to occur. Non-diabetic hypoglycemia is mainly divided into two main groups: insulin-mediated (hyperinsulinism) and insulin-independent. The main causes of hypoglycemia due to endogenous hyperinsulinism are insulinoma and islet cell hyperplasia (nesidioblastosis), post-bariatric surgery, and autoimmune hypoglycemia with the presence of anti-insulin antibodies. Other important causes of hypoglycemia include hypoglycemic drugs, non-islet cell tumors, hormonal deficiencies (primary adrenal insufficiency, anterior pituitary insufficiency), and critical illnesses (liver/kidney failure). In this article, we provide an overview of the pathogenesis and treatment of hypoglycemia.

Keywords : Hypoglycemia, non-diabetic hypoglycemia, insulinoma, nesidioblastosis, postprandial reactive hypoglycemia

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1. Mathew P, Thoppil D. Hypoglycemia. In: StatPearls. Treasure Island(FL): StatPearls Publishing; 2022.
2. Bansal N, Weinstock RS. Non-Diabetic Hypoglycemia. 2020 May 20.In: Feingold KR, Anawalt B, Boyce A (eds). Endotext. South Dartmouth(MA): MDText.com, Inc.; 2000.
3. Yukina M, Katsobashvili I, Platonova N, Troshina E, Mel’nichenko G.Munchausen syndrome with factitious hypoglycemia due to deliberateinsulin analog administration and factitious hyperglycemia in apatient with hypothyroidism. Clin Diabetes Endocrinol. 2022;8(1):8.doi: 10.1186/s40842-022-00145-y
4. Douillard C, Jannin A, Vantyghem MC. Rare causes ofhypoglycemia in adults. Ann Endocrinol (Paris). 2020;81(2-3):110-117. doi: 10.1016/j.ando.2020.04.003
5. Tsujimoto T, Yamamoto-Honda R, Kajio H, et al. High risk ofabnormal QT prolongation in the early morning in diabetic and non-diabetic patients with severe hypoglycemia. Ann Med. 2015;47(3):238-244. doi: 10.3109/07853890.2015.1017528
6. Zhang JW, Zhou YJ. Association of silent hypoglycemia with cardiacevents in non-diabetic subjects with acute myocardial infarctionundergoing primary percutaneous coronary interventions. BMCCardiovasc Disord. 2016;16(1):1-5. doi: 10.1186/s12872-016-0245-z
7. Yun JS, Ko SH. Avoiding or coping with severe hypoglycemia inpatients with type 2 diabetes. Korean J Int Med. 2015;30(1):6-16.doi: 10.3904/kjim.2015.30.1.6
8. Ahmed FW, Majeed MS, Kirresh O. Non-diabetic hypoglycemia. In:StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.
9. Eckert-Norton M, Kirk S. Non-diabetic hypoglycemia. J Clin EndocrinolMetab. 2013;98(10):39A-40A. doi: 10.1210/jc.2013-v98i10.39A
10. Ng CL. Hypoglycaemia in nondiabetic patients - an evidence. Aust FamPhysician. 2010;39(6):399-404.
11. Cox A, Prebtani APH. Nondiabetic Hypoglycemia. McMasterTextbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.24.10.
12. Vella A. Evaluation of postprandial symptoms of hypoglycemia inadults without diabetes. Edits: Nathan DM, Rubinow K. 2022. https://www.uptodate.com/contents/evaluation-of-postprandial-symptoms-of-hypoglycemia-in-adults-without-diabetes
13. Hirshberg B, Livi A, Bartlett DL, et al. Forty-eight-hour fast:the diagnostic test for insulinoma. J Clin Endocrinol Metab.2000;85(9):3222-3226. doi: 10.1210/jcem.85.9.6807
14. Hoff AO, Vassilopoulou-Sellin R. The role of glucagon administrationin the diagnosis and treatment of patients with tumor hypoglycemia.Cancer. 1998;82(8):1585-1592.
15. Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and managementof adult hypoglycemic disorders: an Endocrine Society Clinical PracticeGuideline. J Clin Endocrinol Metab. 2009;94(3):709-728. doi: 10.1210/jc.2008-1410
16. Besser RE, Shields BM, Casas R, Hattersley AT, Ludvigsson J. Lessonsfrom the mixed-meal tolerance test: use of 90-minute and fastingC-peptide in pediatric diabetes. Diabetes Care. 2013;36(2):195-201. doi:10.2337/dc12-0836
17. Ergin A, Hamrahian A, Kennedy A, Gupta, M. 2015. Mixed MealHypoglycemia Test. In: The Cleveland Clinic Manual of DynamicEndocrine Testing. Springer, Cham. doi.org/10. 1007/978-3-319-13048-4_25
18. Téllez-Ávila FI, Acosta-Villavicencio GY, Chan C, et al. Diagnosticyield of endoscopic ultrasound in patients with hypoglicemia andinsulinoma suspected. Endosc Ultrasound. 2015;4(1):52-55. doi:10.4103/2303-9027.151349
19. Nockel P, Babic B, Millo C, et al. Localization of insulinoma using 68Ga-DOTATATE PET/CT scan. J Clin Endocrinol Metab. 2017;102(1):195-199. doi: 10.1210/jc.2016-3445
20. Kalafat H, Mihmanli I, Saribeyoglu K, Belli A. Intraoperativedoppler ultrasound: a reliable diagnostic method in insulinoma.Hepatogastroenterol. 2007;54(76):1256-1258.
21. Zhao K, Patel N, Kulkarni K, Gross JS, Taslakian B. Essentials ofinsulinoma localization with selective arterial calcium stimulation andhepatic venous sampling. J Clin Med. 2020;9(10):3091. doi: 10.3390/jcm9103091
22. Tanaka K, Higuchi R, Mizusawa K, Nakamura T, Nakajima K.Fasting biochemical hypoglycemia and related-factors in non-diabeticpopulation: Kanagawa Investigation of Total Check-up Data fromNational Database-8. World J Diabetes. 2021;12(7):1131-1140. doi:10.4239/wjd.v12.i7.1131
23. Nirantharakumar K, Marshall T, Hodson J, et al. Hypoglycemia in non-diabetic in-patients: clinical or criminal? PLoS One. 2012;7(7):e40384.doi: 10.1371/journal.pone.0040384
24. Oueslati I, Terzi A, Yazidi M, Kamoun E, Chihaoui M. Prevalenceand characteristics of factitious hypoglycaemia in non-diabeticpatients in a department of endocrinology. Endocrinol Diabetes Metab.2022;5(6):e375. doi: 10.1002/edm2.375
25. Shin JJ, Gorden P, Libutti SK. Insulinoma: pathophysiology,localization and management. Future Oncol. 2010;6(2):229-237. doi:10.2217/fon.09.165
26. Tsujino M, Sugiyama T, Nishida K, et al. Noninsulinomapancreatogenous hypoglycemia syndrome: a rare case of adult-onset nesidioblastosis. Intern Med. 2005;44(8):843-847. doi: 10.2169/internalmedicine.44.843
27. Wolfenden T, Dashora U, Carroll P. Hypoglycaemia in a patient whois non-diabetic. BMJ Case Rep. 2014;2014:bcr2013203260. doi: 10.1136/bcr-2013-203260
28. Nadelson J, Epstein A. A rare case of noninsulinoma pancreatogenoushypoglycemia syndrome. Case Rep Gastrointest Med. 2012;2012:164305.doi: 10.1155/2012/164305
29. Douillard C, Mention K, Dobbelaere D, Wemeau JL, Saudubray JM,Vantyghem MC. Hypoglycaemia related to inherited metabolic diseasesin adults. Orphanet J Rare Dis. 2012;7:26. doi: 10.1186/1750-1172-7-26
30. Eisenberg D, Azagury DE, Ghiassi S, Grover BT, Kim JJ. ASMBSposition statement on postprandial hyperinsulinemic hypoglycemiaafter bariatric surgery. Surg Obes Relat Dis. 2017;13(3):371-378. doi:10.1016/j.soard.2016.12.005
31. Mulla CM, Storino A, Yee EU, et al. Insulinoma after bariatricsurgery: diagnostic dilemma and therapeutic approaches. Obes Surg.2016;26(4):874-881. doi: 10.1007/s11695-016-2092-5
32. Singh E, Vella A. Hypoglycemia after gastric bypass surgery. DiabetSpectr. 2012;25(4):218-221.
33. Zhou X, Qian B, Ji N, et al. Pancreatic hyperplasia after gastric bypasssurgery in a GK rat model of non-obese type 2 diabetes. J Endocrinol.2016;228(1):13-23. doi: 10.1530/JOE-14-0701
34. Meier JJ, Butler AE, Galasso R, Butler PC. Hyperinsulinemichypoglycemia after gastric bypass surgery is not accompanied byislet hyperplasia or increased beta-cell turnover. Diabetes Care.2006;29(7):1554-1559. doi: 10.2337/dc06-0392
35. Salehi M, Vella A, McLaughlin T, Patti ME. Hypoglycemia after gastricbypass surgery: current concepts and controversies. J Clin EndocrinolMetab. 2018;103(8):2815-2826. doi: 10.1210/jc.2018-00528
36. Nadelson J, Epstein A. A rare case of noninsulinoma pancreatogenoushypoglycemia syndrome. Case Rep Gastrointest Med. 2012;2012:164305.doi: 10.1155/2012/164305
37. Papamargaritis D, Koukoulis G, Zachari E et al. Dumpingsymptoms and incidence of hypoglycaemia after provocation test at6 and 12 months after laparoscopic sleeve gastrectomy. Obes Surg.2012;22(10):1600-1606. doi: 10.1007/s11695-012-0711-3.
38. Ramadan M, Loureiro M, Laughlan K, et al. Risk of dumpingsyndrome after sleeve gastrectomy and roux-en-y gastric bypass: earlyresults of a multicentre prospective study. Gastroenterol Res Pract.2016;2016:2570237. doi: 10.1155/2016/2570237
39. Altuntas Y. Postprandial reactive hypoglycemia. Med Bull Sisli EtfalHosp. 2019;53(3):215-220. doi: 10.14744/SEMB.2019.59455
40. Alagüney ES, Efe B, Yorulmaz G, Acu B, Durmuş İ. Hypoglycemia dueto the presence of anti-insulin antibodies: a case report. Endocrinol ResPract. 2019;23(1):72-75. doi: 10.25179/tjem.2018-62605
41. Cappellani D, Macchia E, Falorni A, Marchetti P. Insulin autoimmunesyndrome (Hirata disease): a comprehensive review fifty years afterits first description. Diabetes Metab Syndr Obes. 2020;13:963-978. doi:10.2147/DMSO.S219438
42. Roh E, Kim YA, Ku EJ, et al. Two cases of methimazole-inducedinsulin autoimmune syndrome in Graves’ disease. Endocrinol Metab.2013;28(1):55-60. doi: 10.3803/EnM.2013.28.1.55
43. Petersen MC, Graves JM, Yao T, et al. Insulin receptor autoantibody-mediated hypoglycemia in a woman with mixed connective tissuedisease. J Endocr Soc. 2021;6(1):bvab182. doi: 10.1210/ jendso/bvab182
44. Yamasaki H, Yamaguchi Y, Fujita N, et al. Anti-insulin receptorautoantibodies in a patient with type B insulin resistance and fastinghypoglycemia. Acta Diabetol. 2000;37(4):189-196. doi: 10.1007/s005920070004.
45. Chon S, Choi MC, Lee YJ, et al. Autoimmune hypoglycemiain a patient with characterization of insulin receptor autoantibodies.Diabetes Metab J. 2011;35(1):80-85. doi:10.4093/dmj.2011.35.1. 80
46. Ziegler O, Gross P, Kolopp M, Pointel JP, Drouin P. Factitioushypoglycemia mimicking insulinoma. Diabetes Care. 1987;10(3):377-378. doi: 10.2337/diacare.10.3.377c
47. Hirshberg B, Skarulis MC, Pucino F, Csako G, Brennan R, Gorden P.Repaglinide-induced factitious hypoglycemia. J Clin Endocrinol Metab.2001;86(2):475-477. doi: 10.1210/jcem.86.2. 7160.
48. Sousa Filho D, Kanomata EY, Feldman RJ, Maluf Neto A. Munchausensyndrome and Munchausen syndrome by proxy: a narrative review.Einstein (Sao Paulo). 2017;15(4):516-521. doi: 10.1590/S1679-45082017MD3746.
49. Kantarova D, Sagova I, Stancik M, Sadlonova J. Hypoglycemiaassociated with non-islet cell tumors. Neoplasma. 2015;62(6):841-845.doi: 10.4149/neo_2015_102
50. Eren M, Bostan F. Non-pancreatic neuroendocrine tumour presentingwith hypoglycemia in an elderly patient. Afr Health Sci. 2020;20(4):1875-1879. doi: 10.4314/ahs.v20i4.44
51. Ramkumar S, Dhingra A, Jyotsna V, et al. Ectopic insulin secretingneuroendocrine tumor of kidney with recurrent hypoglycemia: adiagnostic dilemma. BMC Endocr Disord. 2014;14:36. doi: 10.1186/1472-6823-14-36
52. Bodnar TW, Acevedo MJ, Pietropaolo M. Management of non-islet-cell tumor hypoglycemia: a clinical review. J Clin Endocrinol Metab.2014;99(3):713-722. doi: 10.1210/jc.2013-3382
53. Ahluwalia N, Attia R, Green A, Cane P, Routledge T. Doege-Pottersyndrome. Ann R Coll Surg Engl. 2015;97(7):e105-e107. doi: 10.1308/rcsann.2015.0023
54. Kalaria T, Ko YL, Issuree KKJ. Literature review: drug and alcohol-induced hypoglycaemia. J Lab Precis Med. 2021;6:21. doi: 10.21037/jlpm-21-16
55. Arky RA. Hypoglycemia associated with liver disease and ethanol.Endocrinol Metab Clin North Am. 1989;18(1):75-90.
56. Centers for Disease Control (CDC). Toxic hypoglycemic syndrome--Jamaica, 1989-1991. MMWR Morb Mortal Wkly Rep. 1992;41(4):53-55
57. Surmaitis R, Hamilton RJ. Ackee Fruit Toxicity. In: StatPearls.StatPearls Publishing, Treasure Island (FL); 2022. PMID: 28613753.
58. Stuart K, Field A, Raju J, Ramachandran S. Postprandial reactivehypoglycaemia: varying presentation patterns on extended glucosetolerance tests and possible therapeutic approaches. Case Rep Med.2013;2013:273957. doi: 10.1155/2013/273957
59. Hirshberg B, Cochran C, Skarulis MC, et al. Malignant insulinoma:spectrum of unusual clinical features. Cancer. 2005;104(2):264-72. doi:10.1002/cncr.21179
Article available in :
Volume 1, Issue 4, 2023
Page : 94-105
https://doi.org/10.51271/ICJIM-0021
Article Information
Received : 01 Eyl 2023
Accepted : 11 Eki 2023
Published : 29 Kas 2023
Corresponding Author :

Türkan Mete: Department of Endocrinology and Metabolism, VM Medical Park Samsun Hospital, Samsun, Turkey

[email protected]
Citation : Mete T, Cesur M. Non-diabetic hypoglycemia. Intercont J Int Med. 2023;1(4):94-105.

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