title: Hypoglycemia due to paraneoplastic secretion of insulin-like growth factor-I in a patient with metastasizing large-cell carcinoma of the lung.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Our findings are compatible with a new form of tumor hypoglycemia caused by circulating tumor-derived IGF-I.
authors.affiliation: Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz, Germany. M.Nauck@diabeteszentrum.de
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.forename: Manfred
authors.initials: M
authors.lastname: Reinecke
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Giorgi
authors.initials: G
authors.lastname: Berishvili
authors.forename: Cornelia
authors.initials: C
authors.lastname: Zwimpfer
authors.forename: Anja M
authors.initials: AM
authors.lastname: Figge
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Paul G
authors.initials: PG
authors.lastname: Lankisch
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zapf
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002850:Chromatography, Gel; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009384:Paraneoplastic Endocrine Syndromes / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001786:Blood Glucose; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D012313:RNA; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D005047:Etoposide; D016190:Carboplatin