Serum Insulin-Like Growth Factor II in 44 Patients with Non-Islet Cell Tumor Hypoglycemia

Abstract

Abstract.Serum insulin-like growth factor II (IGF-II) was characterized by radioimmunoassay and Western immunoblot in 44 patients with non-islet cell tumor hypoglycemia (NICTH). 31 of 44 patients with NICTH had big IGF-II in sera.When the presence of IGF-II in tumors from 20 patients was investigated, IGF-II in tumors was detected in 18 patients and these patients had big IGF-II in sera. In two patients whose tumors did not contain IGF-II, big IGF-II in sera was not detected.In six patients with IGF-II in tumors, hypoglycemia disappeared and the big IGF-II decreased after successful removal of the tumors. These data indicate that the big IGF-II could be related to hypoglycemia, and that the increased serum big IGF-II suggests IGF-II-producing NICTH. Serum IGF-II levels in 31 patients with big IGF-II were greater than those in 13 patients without it (Mean ± SEM: 723 ± 54 vs. 326 ± 31 ng/ml), but the elevated IGF-II levels were found in only 13 patients.Serum IGF-I levels were low in all patients with NICTH.In the 13 patients without big IGF-II, serum IGF-II levels were lower than those in the patients with big IGF-II, and serum IGF-I levels were also low. Serum IGF-II/IGF-I ratios in the patients with big IGF-II were elevated and greater than those in the patients without big IGF-II (35.0 ± 2.2 vs. 11.5 ± 2.4). The present data indicate that IGF-II-producing tumors are not rare in NICTH, and serum big IGF-II and IGF-II/IGF-I ratio are useful for screening patients with IGF-II-producing NICTH.

The coexistence of hypercalcemia and hypoglycemia in a patient with a renal tumor and B cell lymphoma

“…NICHT consists of a rare syndrome characterized by the presence of a solid tumor and severe fasting hypoglycemia determined by an insulin-independent pathway (11). In 1929, Nadler and Wolfer described a case of hypoglycemia associated with liver carcinoma for the first time (11), and Daughaday and cols.…”

“…In 1929, Nadler and Wolfer described a case of hypoglycemia associated with liver carcinoma for the first time (11), and Daughaday and cols. were the first to demonstrate the presence of IGF-2 in a hypoglycemia-producing tumor (12).…”

High Molecular Weight Form Insulin-like Growth Factor II-producing Mesenteric Sarcoma Causing Hypoglycemia

“…Currently, most cases with NICTH are attributed to excessive production of IGF-II by the tumors based on the recent accumulating evidence that these tumors produce and secrete IGF-II (1)(2)(3)(4)(5)(6)(7)(8). The diagnosis of the present patient with NICTH was consistent with that of HMW form IGF-IIproducing tumor causing hypoglycemia for the following reasons: 1) preoperative high IGF-II levels; 2) hypoglycemia improved and serum IGF-II levels decreased to normal after tumor resection; 3) the presence of circulating HMW form IGF-II in patient's serum by Western blotting; 4) the expression of IGF-II mRNA and protein by the tumor as demonstrated by real-time quantitative RT-PCR and immunohistochemistry, respectively.…”

“…The present patient had elevated serum levels of IGF-II consisting predominantly of HMW (approximately 19.8 kDa) form. The HMW form IGF-II has been shown to mimic insulin's effects more effectively than a mature (7.5 kDa) form (1,2,(4)(5)(6)(7)(8). In normal subjects, about two-thirds of the circulating mature form IGF-II is present as a ternary 150 kD complex with IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS).…”

“…The hypoglycemia induced by these tumors can be reversed by tumor resection, but it relapses with recurrence of the tumor. Most of the non-islet cell tumors causing such hypoglycemic symptoms have been found to produce and secrete insulin-like growth factor-II (IGF-II) (1)(2)(3)(4)(5)(6)(7)(8).…”