Bioactive insulin-like growth factors as a possible molecular target for non-islet cell tumor hypoglycemia

Setoyama, Takashi; Miyamoto, Shin’ichi; Horimatsu, Takahiro; Funakoshi, Taro; Nikaido, M; Kodama, Yuzo; Minamiguchi, Sachiko; Yamabata, Tomoko; Muto, Manabu; Chiba, Tsutomu

doi:10.1093/annonc/mdv471.68

Cited by 1 publication

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“…4,5 In this case, all of these criteria were met, and the presence of serum high molecular weight IGF-II and IGF-II expression in the tumor were confirmed. NICTH caused by CRC is extremely rare; to our knowledge, only seven cases have been reported in the English literature, [6][7][8][9][10][11][12] and only two cases have been confirmed as IGF-IIproducing carcinoma by serum high molecular weight IGF-II and tumor IGF-II expression (Table 1). 10,11 All CRCs with NICTH were accompanied by liver metastases.…”

Section: Discussionmentioning

confidence: 99%

“…NICTH caused by CRC is extremely rare; to our knowledge, only seven cases have been reported in the English literature, [6][7][8][9][10][11][12] and only two cases have been confirmed as IGF-IIproducing carcinoma by serum high molecular weight IGF-II and tumor IGF-II expression (Table 1). 10,11 All CRCs with NICTH were accompanied by liver metastases. One case was a small cell carcinoma (neuroendocrine carcinoma), 10 and the remaining six cases were adenocarcinomas.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 All CRCs with NICTH were accompanied by liver metastases. One case was a small cell carcinoma (neuroendocrine carcinoma), 10 and the remaining six cases were adenocarcinomas. [6][7][8][9]11,12 The time from diagnosis to death was less than 13 months in all cases, suggesting a poor prognosis (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9]11,12 The time from diagnosis to death was less than 13 months in all cases, suggesting a poor prognosis (Table 1). [6][7][8][9][10][11][12] Among the eight cases of CRC with NICTH, including this case, this case had the second longest survival period of approximately 12 months from diagnosis to death. Multidisciplinary treatment, including surgery as the first choice, is recommended, 13,14 and glucose and steroid administration are reported to be effective as symptomatic treatments for hypoglycemic attacks.…”

Section: Discussionmentioning

confidence: 99%

“…3 It is considered to be caused by the production of high molecular weight insulin-like growth factor (IGF)-II, which suppresses IGF-I. 4,5 Colorectal carcinoma (CRC) rarely causes NICTH; to our knowledge, only seven cases have been reported in the English literature (Table 1), [6][7][8][9][10][11][12] only two of which were confirmed with both serum high molecular weight IGF-II and tumoral IGF-II, 10,11 with no autopsy case. Herein, we report an autopsy case of IGF-II-producing sigmoid colon carcinoma presenting with NICTH and treatment-resistant hypoglycemic attacks associated with rapid growth of multiple liver metastatic foci after resection of the primary tumor.…”

Section: Introductionmentioning

confidence: 99%

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Insulin‐like growth factor II‐producing colonic carcinoma presenting with non‐islet cell tumor hypoglycemia: An autopsy report revealing neuroendocrine differentiation in the metastatic foci and literature review

Kondo

Hashimoto

Miura

et al. 2022

Pathology International

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Non-islet cell tumor hypoglycemia (NICTH) is a very rare symptom of severe hypoglycemia associated with extrapancreatic tumors. It is considered to be caused by insulin-like growth factor (IGF)-II. There have been no autopsy cases of colorectal carcinoma with NICTH confirmed with both serum high molecular weight and tumoral IGF-II. We report the case of a 46-year-old woman with advanced sigmoid colon cancer and liver metastases. She underwent open sigmoidectomy, and histologically, the lesion was a differentiated-type tubular adenocarcinoma. Postoperative chemotherapy was initiated. However, she experienced repeated hypoglycemia attacks 10 months after the operation, while the liver metastases increased. We examined the cause of hypoglycemia, and finally diagnosed her with NICTH associated with high molecular weight IGF-II production, which was proven by Western immunoblot of the serum. She died 12 months after surgery and was examined by autopsy. Liver metastases showed a transition from adenocarcinoma to carcinoma with neuroendocrine differentiation. Immunohistochemistry showed that both metastatic carcinoma of the liver and primary colonic adenocarcinoma were positive for IGF-II. Neuroendocrine differentiation in liver metastases proven by an autopsy may have contributed to tumor growth, which may have exacerbated the symptoms.

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