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

Autor: Giorgi Berishvili, Manfred Reinecke, Cornelia Zwimpfer, Jan Frystyk, Michael A. Nauck, Werner F. Blum, Wolff Schmiegel, Günter Klöppel, Paul Georg Lankisch, Aurel Perren, Allan Flyvbjerg, Jürgen Zapf, Anja Figge
Rok vydání: 2007
Předmět:
Blood Glucose
medicine.medical_specialty
Lung Neoplasms
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Recurrent hypoglycemia
Clinical Biochemistry
Antineoplastic Agents
In situ hybridization
Hypoglycemia
Biochemistry
Paraneoplastic Endocrine Syndromes
Metastasis
Carboplatin
Insulin-like growth factor
Endocrinology
Insulin-Like Growth Factor II
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Carcinoma
Humans
Insulin
Insulin-Like Growth Factor I
In Situ Hybridization
Etoposide
business.industry
Human Growth Hormone
Reverse Transcriptase Polymerase Chain Reaction
Large cell
Biochemistry (medical)
Middle Aged
medicine.disease
Antineoplastic Agents
Phytogenic
Immunohistochemistry
Insulin-Like Growth Factor Binding Proteins
Lymphatic Metastasis
Chromatography
Gel
Carcinoma
Large Cell
RNA
Female
business
Zdroj: The Journal of clinical endocrinology and metabolism. 92(5)
ISSN: 0021-972X
Popis: 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.The objective was to investigate whether the patient's hypoglycemia was due to excessive IGF-I production by the tumor.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.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.Our findings are compatible with a new form of tumor hypoglycemia caused by circulating tumor-derived IGF-I.
Databáze: OpenAIRE
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