Adult-onset nesidioblastosis: a challenging diagnosis revealed by glucagon-like-peptide-1 receptor imaging
Open accessAbstract
Summary: A 52-year-old female presented with recurrent episodes of fasting or post-absorptive hypoglycemia. A 72-h fasting test confirmed endogenous hyperinsulinemia. Conventional imaging was unremarkable. Selective pancreatic arterial calcium stimulation and hepatic venous sampling showed a maximum calcium-stimulated insulin concentration from several pancreatic areas, mainly the proximal splenic artery and the proximal gastroduodenal artery, suggesting the presence of one or more occult insulinoma(s) in the region of the pancreatic body. 68 Ga-DOTA-exendin-4 PET/CT showed however generalized increased uptake in the pancreas and a diagnosis of nesidioblastosis was therefore suspected. The patient has been since successfully treated with dietetic measures and diazoxide. Treatment efficacy was confirmed by a flash glucose monitoring system with a follow-up of 7 months. Learning points: Adult nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia. The distinction between insulinoma and nesidioblastosis is essential since the therapeutic strategies are different. 68 Ga-DOTA-exendin-4 PET/CT emerges as a new noninvasive diagnostic tool for the localization of an endogenous source of hyperinsulinemic hypoglycemia. Medical management with dietetic measures and diazoxide need to be considered as a valuable option to treat patients with adult nesidioblastosis. Flash glucose monitoring system is helpful for the evaluation of treatment efficacy.
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This imaging modality couples exendin-4, a GLP-1RA with radioactive tracer, allowing for demonstration of multifocal pancreatic involvement, a hallmark of NIPHS.
“This imaging modality couples exendin-4, a GLP-1RA with radioactive tracer, allowing for demonstration of multifocal pancreatic involvement, a hallmark of NIPHS [100].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [100]
The Discussion describes radiolabeled exendin-4 as a GLP-1 receptor imaging tracer. The Investigation reports that PET/CT showed generalized, moderate uptake throughout the pancreas, without focal uptake; it does not show multifocal lesions or identify multifocal involvement as a hallmark of NIPHS. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFunctional imaging with 68Ga-DOTA-Exendin-4 PET/CT is less invasive and may be just as sensitive as selective arterial calcium stimulation testing (SACST) in differentiating between insulinomas and NIPHS.
“More recent research suggests that functional imaging with 68Ga-DOTA-Exendin-4 PET/CT is less invasive and may be just as sensitive as selective arterial calcium stimulation testing (SACST) in differentiating between insulinomas vs. NIPHS [100].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [100]
The Discussion describes 68Ga-DOTA-exendin-4 PET/CT as noninvasive and suggests it could distinguish occult insulinoma from diffuse nesidioblastosis. It reports sensitivity of 94.6% for detecting insulinomas and 67–100% for SACST in localizing them, but does not establish that the two tests are equally sensitive at differentiating insulinoma from nesidioblastosis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn severe or refractory NIPHS, partial or subtotal pancreatectomy is helpful in up to 50% of cases.
“In severe or refractory cases, NIPHS management may include either partial or subtotal pancreatectomy, which is helpful in up to 50% of cases [55,100].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [100]
The Discussion reports that partial pancreatectomy (60–80% resection) controls nesidioblastosis in 50% of patients without additional medication, especially in focal forms. It does not specifically give that outcome for severe or refractory NIPHS, or separately evaluate subtotal pancreatectomy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPancreatic β-cells appear to have a higher density of GLP-1R in NIPHS, which may augment insulin sensitivity and secretion.
“Lastly, pancreatic β -cells appear to have a higher density of GLP-1R in this condition, which may augment insulin sensitivity and secretion [100].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [100]
The Discussion states that GLP-1R density in nesidioblastosis is higher than in the normal pancreas, supporting the receptor-density part of the claim. The paper does not say that this higher density augments insulin sensitivity or secretion; the Investigation reports increased insulin secretion after calcium stimulation, but does not link it to GLP-1R density. No page numbers are available in our copy. (LLM, conf=0.85)
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Cites
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Non-Diabetic Hypoglycemia: Evaluation and Management in Adults
Looi, E., & Lawler, H. M. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134393 · Cited by 10 · see citing works
“Lastly, pancreatic β -cells appear to have a higher density of GLP-1R in this condition, which may augment insulin sensitivity and secretion [100].”
Influential
- Authors
- Demartin, S., Goffette, P., Christ, E., Freitag, M. T., Maiter, D., & Maria Furnica, R.
- Affiliations
- Cliniques Universitaires Saint-Luc (BE)
- University of Basel (CH)
- Department of Endocrinology, Université catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium
- Corresponding author
- Demartin, Sophie
- Venue
- Endocrinology, Diabetes & Metabolism Case Reports
- Publisher
- Bioscientifica
- Published
- 2022-11-01
- Volume
- 2022
- ISSN
- 2052-0573 (ISSN-L)
- PMC
- PMC9716366
- OpenAlex
- W4310461260
- Cited by
- 9
- References
- 4
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Endocrinology Diabetes and Metabolism Case Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- hyperinsulinemic hypoglycemia, insulinoma, hepatic venous sampling, diazoxide, flash glucose monitoring, differential diagnosis
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