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Cited by 63Growth Hormone and Insulin-like Growth FactorsNeuroendocrine Tumor Research AdvancesPituitary Gland Disorders and Treatments

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Hypoglycemia due to paraneoplastic secretion of insulin-like growth factor-I in a patient with metastasizing large-cell carcinoma of the lung.

Nauck, Michael A., Reinecke, Manfred, Perren, Aurel, Frystyk, Jan, Berishvili, Giorgi, Zwimpfer, Cornelia, Figge, Anja M., Flyvbjerg, Allan, Lankisch, Paul G., Blum, Werner F., Klöppel, Günter, Schmiegel, Wolff, Zapf, Jürgen·2007·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2006-2573
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Abstract

CONTEXT: Nonpancreatic tumors may cause recurrent hypoglycemia known as nonislet cell tumor hypoglycemia. It is due to overproduction and secretion by the tumor of incompletely processed IGF-II, termed big IGF-II. We recently identified a patient with recurrent hypoglycemia and low insulin, but without elevated big IGF-II. Multiple small lung nodules were detected by computed tomography scan. An undifferentiated large-cell carcinoma was diagnosed from an axillary lymph node metastasis. OBJECTIVE: The objective was to investigate whether the patient's hypoglycemia was due to excessive IGF-I production by the tumor. METHODS: Serum IGF- I and IGF-II, insulin, and GH were measured by RIA; the distribution of IGFs between IGF binding protein complexes in serum was analyzed after neutral gel filtration. Tissue IGF-I was identified by immunohistochemistry and in situ hybridization, and by RT-PCR after RNA extraction. RESULTS: Total and free serum IGF-I, but not total, free, and big IGF-II, was increased, and the IGF-I content of the two IGF binding protein complexes was elevated. Immunohistochemistry demonstrated IGF-I peptide in situ hybridization IGF-I mRNA in the lymph node metastasis. Combined GH/glucocorticoid treatment prevented hypoglycemia, but did not lower IGF-I. After chemotherapy with carboplatinum/etoposide, the lung nodules largely regressed, and serum IGF-I and the IGF-I content of the two binding protein complexes became normal. Hypoglycemia did not recur despite discontinuation of GH/glucocorticoid treatment. CONCLUSION: Our findings are compatible with a new form of tumor hypoglycemia caused by circulating tumor-derived IGF-I.

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  • Although hypoglycemia in patients with nonislet cell tumors is often the result of tumor overproduction of incompletely processed IGF-II, hypoglycemia attributed to overproduction of IGF-I has also been reported.

    “Although hypoglycemia in patients with nonislet cell tu- mors is often the result of tumor overproduction of incompletely processed IGF-II (27), hypoglycemia attributed to overproduction of IGF-I has also been reported (28).”

    From Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline (2009) · cites this paper as [28]

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Metadata

Authors
Nauck, M. A., Reinecke, M., Perren, A., Frystyk, J., Berishvili, G., Zwimpfer, C., Figge, A. M., Flyvbjerg, A., Lankisch, P. G., Blum, W. F., Klöppel, G., Schmiegel, W., & Zapf, J.
Affiliations
  • Universitätsklinikum Knappschaftskrankenhaus Bochum (DE)
  • University of Zurich (CH)
  • University Hospital Zurich (CH)
  • Aarhus University Hospital (DK)
  • Klinikum Lüneburg (DE)
  • Justus-Liebig-Universität Gießen (DE)
  • Department of Pathology (G.K.), Christian-Albrecht-University, D-24105 Kiel, Germany
  • Division of Neuroendocrinology (M.R., G.B., J.Z.), Institute of Anatomy, University of Zurich, Switzerland
Corresponding author
Nauck, Michael A.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2007-05-01
Volume
92
Issue
5
Pages
1600-1605
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2006-2573
OpenAlex
W2065960043
Semantic Scholar
c42c46571a785d380dcd4207a62ccf0973669c33
Cited by
63
References
30
Citations by year
2026: 1 · 2025: 6 · 2024: 2 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 2 · 2012: 1
FWCI
4.14
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (46808)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
tumor-induced hypoglycemia, insulin-like growth factor I, paraneoplastic syndrome, large cell lung carcinoma, lung metastasis, insulin-like growth factor II, IGF binding proteins, growth hormone therapy, glucocorticoid therapy, carboplatin, etoposide, IGF-I mRNA expression
MeSH terms
Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Antineoplastic Agents, Phytogenic, Blood Glucose, Chromatography, Gel, Etoposide, Female, Humans, Hypoglycemia, Immunohistochemistry, Insulin, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Lung Neoplasms, Lymphatic Metastasis, Middle Aged, Paraneoplastic Endocrine Syndromes, RNA, Carboplatin, In Situ Hybridization, Carcinoma, Large Cell, Insulin-Like Growth Factor Binding Proteins, Human Growth Hormone, Reverse Transcriptase Polymerase Chain Reaction

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