Hyperinsulinemic hypoglycemia with nesidioblastosis: histologic features and growth factor expression
Open accessAbstract
Hypoglycemia secondary to nesidioblastosis is rare in adults, and the pathogenesis of this condition is unknown. To determine factors leading to nesidioblastosis in adults, we analyzed 36 cases of nesidioblastosis including 27 cases of postgastric bypass nesidioblastosis and 9 cases of idiopathic nesidioblastosis in adults by immunohistochemistry using antibodies to insulin-like growth factor 1, insulin-like growth factor 2 (IGF2), insulin-like growth factor one receptor-alpha epidermal growth factor receptor, transforming growth factor-beta1 and 2, and transforming growth factor-beta receptor type 3. Fifty-two surgically excised pancreatic specimens from patients with benign exocrine tumors and no evidence of hypoglycemia were used as controls. There was increased IGF2, insulin-like growth factor receptor 1 receptor-alpha and transforming growth factor-beta receptor 3 expression in islets from nesidioblastosis patients compared to controls. Peliosis-type vascular ectasia was more common in nesidioblastosis patients compared to controls. These findings suggest that increased production of growth factors and growth factor receptors may contribute to the development of nesidioblastosis in adults.
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Pancreatic resection, the most commonly reported procedure, was performed in approximately 67% of patients.
“Pancreatic resection, the most commonly reported procedure, was performed in approximately 67% of patients (66,103,105,107,114,116-123).”
From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [119]
The Tissue section (page unavailable) reports that all 36 selected patients with nesidioblastosis underwent partial pancreatectomy, so the paper documents pancreatic resection. It does not report that resection was the most commonly performed procedure or that approximately 67% of patients underwent it; the surgical history was a selection criterion for this cohort. (LLM, conf=0.86)
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“Increased production of a β cell trophic peptide, including insulin-like growth factor (IGF) 2, IGF 1 receptor-α, and transforming growth factor-β receptor 3, may contribute to the development of postgastric bypass nesidioblastosis in adults.(9) In fact, there are reported cases of nesidioblastosis associated with pre…”
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“18 However, the developmental mechanism of adult-onset nesidioblastosis remains unclear, and several causes have been speculated, including dysregulation of beta cell function, 19 increased production of growth factors, 20 and unidentified genetic mutations.”
Nesidioblastosis in a simmental calf.
Gacar, A., Pekmezci, D., Karayigit, M., Kabak, Y., & Gülbahar, M. (2012) · Journal of Comparative Pathology · doi:10.1016/j.jcpa.2012.04.002 · Cited by 3 · see citing works
Nesidioblastosis post-bariatric surgery in an adult patient: a case report and review of literature
Abdul-Hafez, H., Rabi, K., Sarama, A., Melhem, L., Abed, W., & Maree, M. (2025) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000003198 · Cited by 2 · see citing works
“This indicates that these growth factors might contribute to the onset of nesidioblastosis by stimulating beta-cell hyperplasia and hypertrophy [ 14 ] .”
Zhu, G.-W., Xie, L., & Hu, X.-W. (2023) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2023.12330 · Cited by 2 · see citing works
González, I., Kang, L., Williams, G. A., Liu, J., DeNardo, D. G., Hawkins, W. G., & Chatterjee, D. (2020) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001454 · Cited by 1 · see citing works
Spontaneous Hypoglycemia in a Non-diabetic Patient: A Diagnostic and Therapeutic Conundrum
Mahendiran, K., Moorthy, S., M., L., & Bhaskar, E. (2024) · Cureus · doi:10.7759/cureus.65467 · Cited by 1 · see citing works
“Certain authors have observed vascular ectasia within the islets among patients with hyperinsulinemic hypoglycemia [7].”
BackgroundA case of insulinoma confused with dumping syndrome after total gastrectomy
Bilen, A., Mercantepe, F., Bilen, H., & Çapoĝlu, I. (2022) · Journal of Surgery and Medicine · doi:10.28982/josam.993536 · Cited by 1
“A previous history of gastric bypass surgery was present in 27 patients [11].”
BackgroundPostprandial Hyperinsulinemic Hypoglycemia in Bariatric Surgery
de Heide, L. D., Emous, M., & van Beek, A. V. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804011-9.00054-6 · Cited by 1 · see citing works
[Nesidioblastosis (diagnosis, surgical treatment)].
Kriger, A., Smirnov, A., Kalinin, D., Glotov, A., Berelavichus, S., Konyaeva, G. I., Lebedeva, A. N., Karel'skaya, N. A., & Tsygankov, V. N. (2015) · Khirurgiia · doi:10.17116/hirurgia20151016-29 · Cited by 1 · see citing works
Hypoglycémie après bypass gastrique : mise au point au sujet des mécanismes et des traitements
Ritz, P., Vaurs, C., Barigou, M., & Hanaire, H. (2015) · Médecine des Maladies Métaboliques · doi:10.1016/s1957-2557(15)30201-7 · Cited by 1 · see citing works
A Rare Case of Idiopathic Rapid Gastric Emptying
Vohra, S., Pinto, Y. E., & Raja, K. (2026) · Cureus · doi:10.7759/cureus.106710
“Increased periductular islets, larger β -cell nuclei, and increased islet size and quantity were among the early histopathologic findings of nesidioblastosis [6].”
Bavaria, S., Chana, A., Nurani, K., & Kimang’a, J. (2026) · World Journal of Diabetes · doi:10.4239/wjd.v17.i3.116660
A rare cause of hypoglycemia in adults
Avetisian, G. R., Tsinoeva, Z. R., Altshuler, N., Moskalets, E. R., Glazunov, P. A., Bunova, S., & Zhilyayev, E. V. (2023) · The Clinician · doi:10.17650/1818-8338-2022-16-4-k668
Gottsponer, J. A., Baker, D. L., Osborn, T., Estrada, M., Giorgakis, E., Burdine, L., & Patel, R. B. (2023) · Journal of Surgical Case Reports · doi:10.1093/jscr/rjad050
“In contrast to insulinoma, which is a proliferation of β-islet cells in a discrete, localized pancreatic mass, nesidioblastosis is characterized by diffuse proliferation of enlarged β-islet cells interspersed throughout the pancreas [1, 2].”
BackgroundEndurtekin krampaköst hjá ungri konu – sjúkratilfelli
Gunnarsdóttir, G., Guðmundsdóttir, A., Hellman, P., & Stålberg, P. (2016) · Læknablaðið · doi:10.17992/lbl.2016.0708.92
[Nesidioblastosis in the adult: a case report].
Ramirez-Gonzalez, L., Sotelo-Álvarez, J. A., Rojas-Rubio, P., Macías-Amezcua, M. D., Orozco-Rubio, R., & Fuentes-Orozco, C. (2015) · Cirugía y Cirujanos (English Edition) · doi:10.1016/j.circen.2015.09.006
Reactive Hypoglycemia Associated with Mild Adrenal Dysfunction, So-called Adrenal Fatigue
Yamaguchi, H., Kobayashi, A., Shirakami, A., & Hashimoto, N. (2015) · International Journal of Medical and Pharmaceutical Case Reports · doi:10.9734/ijmpcr/2015/12994
“In small series and case reports, NIPHS has clinical features of a male dominance (70%), postprandial hypoglycemia, neuroglycopenic symptoms, and a history of upper gastrointestinal surgery in 40% of the patients (not gastric bypass) [28,29,30,31].”
BackgroundHypoglycemia after Roux-en-Y Gastric Bypass Surgery
Roque, S., Nambi, S., & Rothkopf, M. (2014) · doi:10.1201/b17616-21
Hypoglycemia After Gastric Bypass
Alvarez, G. D. C. (2020) · Gastric Bypass · doi:10.1007/978-3-030-28803-7_35
An Approach to Hypoglycemic Disorders
Vella, A. (2015) · The Endocrine Society eBooks · doi:10.1210/mtp4.9781936704941.ch21
Self-citation
- Authors
- Rumilla, K. M., Erickson, L. A., Service, F. J., Vella, A., Thompson, G. B., Grant, C. S., & Lloyd, R. V.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Lloyd, Ricardo V
- Venue
- Modern Pathology
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 22
- Issue
- 2
- Pages
- 239-245
- ISSN
- 0893-3952 (ISSN-L)
- OpenAlex
- W1986323441
- Cited by
- 85
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 9 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 4 · 2017: 2 · 2016: 12 · 2015: 12 · 2014: 8 · 2013: 4 · 2012: 7
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Modern Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- nesidioblastosis, hyperinsulinemic hypoglycemia, insulin-like growth factor II, insulin-like growth factor I, IGF-1 receptor, epidermal growth factor receptor, TGF-β1, pancreatic islets, peliosis, angiodysplasia, growth factor expression
- MeSH terms
- Adult, Blood Vessels, Female, Humans, Hyperinsulinism, Hypoglycemia, Immunohistochemistry, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Islets of Langerhans, Male, Middle Aged, Proteoglycans, Risk Factors, Gastric Bypass, Case-Control Studies, In Situ Hybridization, Receptor, IGF Type 1, Receptors, Transforming Growth Factor beta, Intercellular Signaling Peptides and Proteins, Nesidioblastosis, Transforming Growth Factor beta1, Transforming Growth Factor beta2
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