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Cited by 19Pancreatic function and diabetesNeuroendocrine Tumor Research AdvancesPancreatitis Pathology and Treatment

Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS): Review of the Literature of a Rare Cause of Hyperinsulinemic Hypoglycemia

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Dieterle, Martin Philipp, Husari, Ayman, Prozmann, Sophie Nicole, Wiethoff, Hendrik, Stenzinger, Albrecht, Röhrich, Manuel, Pfeiffer, Uwe, Kießling, Wolfgang Rüdiger +6 more·2023·Biomedicines
DOI 10.3390/biomedicines11061732PMC PMC10296556
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Abstract

Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional β-cell disorders. The latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked. A combination of careful clinical assessment, oral glucose tolerance testing, 72 h fasting, sectional and functional imaging, and invasive insulin measurements can lead to the correct diagnosis. Due to a lack of a pathophysiological understanding of the condition, conservative treatment options are limited and mostly ineffective. Therefore, nearly all patients currently undergo surgical resection of parts or the entire pancreas. Consequently, apart from faster diagnosis, more elaborate and less invasive treatment options are needed to relieve the patients from the dangerous and devastating symptoms. Based on a case of a 23-year-old man presenting with this disease in our department, we performed an extensive review of the medical literature dealing with this condition and herein presented a comprehensive discussion of this interesting disease, including all aspects from epidemiology to therapy.

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  • NIPHS is considerably rarer than insulinomas with an estimated annual incidence of 0.5-5%.

    “The incidence of noninsulinoma pancreatogenous hypoglycemic syndrome (NIPHS) is difficult to ascertain, but is considerably rarer than insulinomas with an estimated annual incidence of 0.5-5% [55].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [55]

    Section 6 (Epidemiology; page not supplied) describes NIPHS/nesidioblastosis as rarer than insulinoma and says its true incidence remains unknown. Its 0.5–5% figure is the estimated proportion of adult hyperinsulinemic hypoglycemia cases attributed to nesidioblastosis, not an annual incidence; the review instead estimates 2–20 cases per 100 million persons per year. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • In 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 [55]

    Section 9 (Therapy; page not provided) says partial or subtotal pancreatectomy may be needed to control symptoms, but it gives no figure for the proportion of cases helped. Its 50–60% figure describes the extent of a limited pancreatic resection, not a treatment success rate; the section also notes that symptoms can recur. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • The hypothesis that nesidioblastosis is associated with PBH pathophysiology is controversial, as this histopathologic diagnosis has been made in patients with PBH.

    “The hypothesis that nesidioblastosis is associated with PBH pathophysiology is a controversial subject, as this histopathologic diagnosis has been made in patients with PBH [55].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [55]

  • Nesidioblastosis may be found in a wide variety of disorders and may occur without evidence of hyperinsulinemia or hypoglycemia.

    “Nesidioblastosis may be found in a wide variety of disorders and may occur without evidence of hyperinsulinemia or hypoglycemia [55].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [55]

  • 72-hour fasts are expected to be negative in NIPHS, although there have been reports of positive testing.

    “Seventy-two hour fasts are expected to be negative, although there has been reports of positive testing in such patients [55].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [55]

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Authors
Dieterle, M. P., Husari, A., Prozmann, S. N., Wiethoff, H., Stenzinger, A., Röhrich, M., Pfeiffer, U., Kießling, W. R., Engel, H., Sourij, H., Steinberg, T., Tomakidi, P., Kopf, S., & Szendroedi, J.
Affiliations
  • University of Freiburg (DE)
  • University Hospital Heidelberg (DE)
  • Pfalzklinikum for Psychiatry and Neurology AdÖR, Weinstr. 100, 76889 Klingenmünster, Germany
  • Independent Researcher of Neurology and Psychiatry, 72250 Freudenstadt, Germany
  • German Cancer Research Center (DE)
  • Medical University of Graz (AT)
  • Heidelberg University (DE)
Corresponding author
Dieterle, Martin Philipp
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2023-06-16
Volume
11
Issue
6
Pages
1732
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines11061732
PMC
PMC10296556
OpenAlex
W4380988303
Cited by
19
References
443
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 2
FWCI
1.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Keywords
nesidioblastosis, hyperinsulinemic hypoglycemia, differential diagnosis, beta-cell dysfunction, oral glucose tolerance test, fasting hypoglycemia, pancreatic resection, conservative treatment

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