Synthesis and secretion of insulin-like growth factor II by a leiomyosarcoma with associated hypoglycemia

N Engl J Med. 1988 Dec 1;319(22):1434-40. doi: 10.1056/NEJM198812013192202.


We describe a case of recurrent hypoglycemia apparently caused by secretion of insulin-like growth factor II (IGF-II) by a leiomyosarcoma. A 67-year-old woman presented with recurrent severe hypoglycemia and a large mass in the thorax. During hypoglycemia, plasma cortisol was elevated, but insulin and growth hormone levels were low. After resection of a large leiomyosarcoma, the hypoglycemia resolved. After an eight-year remission, both the tumor and symptomatic hypoglycemia recurred. During a second operation a second large tumor was removed, with relief of the patient's hypoglycemia. The tumor contained high concentrations of IGF-II mRNA and 2100 ng of IGF-II immunoreactive peptide per gram. Filtration through a BioGel P-60 gel column established that 77 percent of the IGF-II was present as a larger molecule, demonstrating incomplete processing of the pro-IGF-II peptides. A similar fraction of high-molecular-weight IGF-II was present in the serum, indicating that the tumor was the chief source of IGF-II. The high-molecular-weight IGF-II found in both the tumor and serum was fully reactive with the IGF-II receptor. Radioimmunoassay showed that the concentrations of insulin-like growth factor I (IGF-I) in tumor and serum were low, suggesting feedback inhibition of growth hormone secretion by IGF-II. Eight months after reoperation, plasma concentrations of IGF-I and IGF-II were normal, and high-molecular-weight IGF-II was virtually undetectable. We conclude that the most likely cause of this patient's recurrent hypoglycemia was IGF-II produced by the leiomyosarcoma.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • DNA / analysis
  • Female
  • Humans
  • Hypoglycemia / etiology*
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor II / biosynthesis
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • Leiomyosarcoma / complications
  • Leiomyosarcoma / metabolism*
  • Molecular Weight
  • Paraneoplastic Syndromes / etiology
  • RNA, Messenger / analysis
  • Somatomedins / metabolism*
  • Thoracic Neoplasms / complications
  • Thoracic Neoplasms / metabolism*


  • RNA, Messenger
  • Somatomedins
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • DNA