title: Severe hypoglycemia with "Big"-IGF-2 oversecretion by a giant phyllode tumor of the breast: a rare case of non-islet cell tumor-induced hypoglycemia (NICTH).
abstract: OBJECTIVE
  We report an exceptional case of non-islet cell tumor-induced hypoglycemia (NICTH) secondary to "Big"-IGF-2 oversecretion due to a giant phyllode tumor of the breast.
  
  
  METHODS
  A 49-year-old woman was admitted in emergency for brutal neurologic defect revealing severe hypoglycemia. Several similar episodes were observed throughout hospitalization, requiring continue perfusion of hypertonic glucose solution. Beside these metabolic disorders, we observed a giant and hard tumor of the left breast (about 30cm in diameter).
  
  
  CONCLUSIONS
  Supplementary blood analysis revealed serum levels of C-peptide and insulin suppressed during hypoglycemia, excluding the possibility of either endogenous or exogenous hyperinsulinism. Low plasma levels of GH and IGF-1 were found, suggesting a negative feedback loop on somatotroph axis function. Therefore, the hypothesis of an insulinomimetic compound released by tumor cells was evoked because of abnormal presence of high-weight and immature form of IGF-2 (called "Big"-IGF-2) in the serum identified by western immunoblot analysis. A left mastectomy was performed and completely restored glucose homeostasis and confirmed the paraneoplastic origin of hypoglycemia because of markedly elevated expression of IGF-2 mRNA (qPCR) within the tumor cells. Finally, the anatomopathology analysis diagnosed a mesenchymatous tumor, namely a high-grade phyllode sarcoma of the breast.
  
  
  CONCLUSIONS
  Although NICTH due to "Big"-IGF-2 overproduction is a rare phenomenon, mainly observed in case of mesenchymatous tumor, it should be considered in presence of severe hypoglycemia with voluminous tumor and without hyperinsulinism.
authors.affiliation: Department of Endocrinology, University Hospital of Nancy, allée de Morvan, 54500 Vandoeuvre-Les-Nancy, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Renard
authors.forename: Christelle
authors.initials: C
authors.lastname: Langbour-Remy
authors.forename: Marc
authors.initials: M
authors.lastname: Klein
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Bouc
authors.forename: Georges
authors.initials: G
authors.lastname: Weryha
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuny
mesh_terms: D001943:Breast Neoplasms / Q000150:complications* / Q000378:metabolism* / Q000601:surgery; D002096:C-Peptide / Q000097:blood; D017809:Fatal Outcome; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology* / Q000628:therapy; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008408:Mastectomy; D008875:Middle Aged; D003557:Phyllodes Tumor / Q000150:complications* / Q000378:metabolism* / Q000601:surgery; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism*
chemical_list: D002096:C-Peptide; D007328:Insulin; D011498:Protein Precursors; C066038:proinsulin-like growth factor II; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II