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Cited by 222Growth Hormone and Insulin-like Growth FactorsPituitary Gland Disorders and TreatmentsNeuroendocrine Tumor Research Advances

Non-Islet Cell Tumour-Induced Hypoglycaemia: A Review of the Literature Including Two New Cases

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de Groot, J. W. B, Rikhof, B., van Doorn, J., Bilo, H. J G, Alleman, M. A, Honkoop, A. H, van der Graaf, W. T A·2007·Endocrine Related Cancer
DOI 10.1677/erc-07-0161
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Abstract

This review focuses on the tumour types and symptoms associated with non-islet cell tumour-induced hypoglycaemia (NICTH) as well as the pathogenesis, diagnosis and treatment of this rare paraneoplastic phenomenon. In addition, we report two illustrative cases of patients suffering from NICTH caused by a solid fibrous tumour and a haemangiopericytoma respectively. In the first case, NICTH resolved following complete resection of the tumour, but in the second case the patient needed long-term treatment aimed at controlling hypoglycaemia because of non-resectable metastases. Many tumour types have been associated with NICTH. The crucial event in the development of NICTH seems to be overexpression of the IGF-II gene by the tumour. NICTH is characterised by recurrent fasting hypoglycaemia and is associated with the secretion of incompletely processed precursors of IGF-II ('big'-IGF-II) by the tumour. This induces dramatic secondary changes in the circulating levels of insulin, GH, IGF-I and IGF-binding proteins, resulting in an insulin-like hypoglycaemic activity of 'big'-IGF-II.

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  • Glucocorticoids alleviate hypoglycemia by stimulating gluconeogenesis and suppressing production of big IGF-II.

    “Glucocorticoids alleviate hypoglycemia by stimulating gluconeogenesis and suppressing production of big IGF-II [43].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [43]

    The Glucocorticosteroids section says treatment seems to relieve hypoglycaemia by stimulating glyconeogenesis and suppressing big-IGF-II production. It qualifies the suppression as occurring “although not in all cases,” which the citing sentence omits. No page number is provided in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Overall, hepatocellular carcinomas and stomach cancers are the most common causes of NICTH and comprise ~16% and 8% of cases, respectively.

    “Overall, hepatocellular carcinomas and stomach cancers are the most common causes of NICTH and comprise ~16% and 8% of cases, respectively.”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [43]

  • The etiology of NICTH has been ascribed to IGF-II, which shares structural homology with insulin but has a ~10-fold lesser glucose lowering effect.

    “The etiology has been ascribed to insulinlike growth factor-II (IGF-II), which shares structural homology with insulin but has a ~10-fold lesser glucose lowering effect [43].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [43]

  • NICTH is typically caused by either mesenchymal (41%) or epithelial solid tumors (43%).

    “NICTH is typically caused by either mesenchymal (41%) or epithelial solid tumors (43%) [43].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [43]

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Cited by

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Authors
de Groot, J. W. B., Rikhof, B., van Doorn, J., Bilo, H. J. G., Alleman, M. A., Honkoop, A. H., & van der Graaf, W. T. A.
Affiliations
  • Isala (NL)
  • University Medical Center Groningen (NL)
ORCID
Venue
Endocrine Related Cancer
Publisher
Bioscientifica
Published
2007-12-01
Volume
14
Issue
4
Pages
979-993
ISSN
  • 1351-0088 (ISSN-L)
  • 1479-6821
DOI
10.1677/erc-07-0161
OpenAlex
W2117166979
Cited by
222
References
0
Citations by year
2026: 9 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 14 · 2021: 12 · 2020: 17 · 2019: 14 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 14 · 2014: 13 · 2013: 26 · 2012: 12
FWCI
6.52
Type
journal article
Language
en
Open access
Locations
  • Endocrine Related Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
Keywords
fibrous tumor, hemangiopericytoma, fasting hypoglycaemia, insulin-like activity, IGF binding proteins, tumor resection, metastatic disease, pathogenesis
MeSH terms
Aged, 80 and over, Blood Glucose, Female, Humans, Hypoglycemia, Insulin-Like Growth Factor II, Male, Middle Aged, Palliative Care, Pancreatic Neoplasms, RNA, Messenger

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