Synthesis and secretion of insulin-like growth factor II by a leiomyosarcoma with associated hypoglycemia.
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.
Daughaday
W H
WH
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Emanuele
M A
MA
Brooks
M H
MH
Barbato
A L
AL
Kapadia
M
M
Rotwein
P
P
D000368:Aged; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007890:Leiomyosarcoma / Q000150:complications / Q000378:metabolism*; D008970:Molecular Weight; D010257:Paraneoplastic Syndromes / Q000209:etiology; D012333:RNA, Messenger / Q000032:analysis; D013002:Somatomedins / Q000378:metabolism*; D013899:Thoracic Neoplasms / Q000150:complications / Q000378:metabolism*
D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA