A case of insulin-like growth factor 2-producing gastrointestinal stromal tumor with severe hypoglycemia

Abstract

Background Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome that secretes incompletely processed high molecular weight insulin growth factor 2 (big-IGF2), which results in stimulation of the insulin receptor and subsequently induces hypoglycemia. Gastrointestinal stromal tumor (GIST) is a common intestinal mesenchymal neoplasm of the gastrointestinal tract. The most frequent site of GIST is the stomach; NICTH induced by IGF2-producing stomach GISTs is rare. Case presentation An 84-year-old man was admitted to the hospital due to impaired consciousness (JCS II-10) in the morning. At the time of admission, his serum glucose was 44 mg/dL; his consciousness was restored with 20 ml of 50% glucose. To avoid hypoglycemia, a continuous intravenous infusion of glucose as well as dietary intervention was required. At the time of hypoglycemia, the levels of insulin and C-peptide were suppressed. Additionally, IGF1 levels were below the normal range. Abdominal computed tomography revealed that he had a large lobulated mass (116 × 70 × 72 mm) around the gastric corpus. Pathological analysis of biopsy specimens identified disarray of spindle cells and positivity for c-kit as well as strong positivity for DOG-1. Further analysis revealed high levels of Ki-67 (Mib-1 index: 15.5%) and mitotic index (7/50HPF); the tumor was diagnosed as high-risk GIST, and complete surgical resection was performed. Hypoglycemia resolved immediately after tumor resection. The resected tumor specimen was positive for IGF2 staining, and big-IGF2 (11–18 kDa) was detected in preoperative serum and tumor samples; the patient was diagnosed with NICTH due to an IGF2-producing tumor. Conclusions NICTH is rare in GIST of the stomach; however, the large GIST could produce big-IGF2 and subsequently cause severe hypoglycemia, requiring prompt evaluation and complete tumor resection.

Severe Non-Islet Cell Hypoglycemia From Ileum-Origin Gastrointestinal Stromal Tumor Producing Insulin-Like Growth Factor-2 in a Patient With Liver Cirrhosis Due to Chronic Hepatitis B

“…One of the possible reasons is counter regulatory response to the severe hypoglycemia because it is known that GH is counter hormone for hypoglycemia as well as other hormones such as adrenalin, noradrenalin and cortisol; these hormones in addition to GH also were not at least inhibited in this case. However GH in the patient with NICTH was largely inhibited at the time when the severe hypoglycemia occurred in previous reports [14,16]. We consider that the complication of acromegaly as the cause of the elevation of GH is improbable because of the lack of clinical findings, such as characteristic facial configuration and swelling of the fingers; although we missed the opportunity to use pituitary magnetic resonance imaging (MRI).…”

“…It is unlikely that hypothyroid influenced the hypoglycemia in our case because the hypothyroid was latent. Therefore, we next suspected NICTH due to GIST, although GIST related-NICTH is very rare [ 13 - 16 ]. As expected, additional immunohistochemical staining with an anti-IGF-2 antibody of the resected tumor tissues was positive, which strongly suggested GIST related-NICTH.…”

“…GIST in most patients is involved in oncogenic mutations and overexpression of the tyrosine kinase receptor KIT [12]. Although GIST is included among the mesenchymal tumors, NICTH associated with GIST is very rare [13][14][15][16]; and to our knowledge there have been no previous reports of NICTH in patients with GIST complicated with liver cirrhosis, which may sometimes be the cause of hypoglycemia [17][18][19].…”

Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD

“…Increased levels of IGF2 in comparison to controls, in multiple diseases including cancer and diabetes have been detected [ 47 ]. In brief, associations of increased serum levels of IGF2 with hypoglycaemia [ 48 ] as well as of total and free IGF2 (defined as bound or unbound fractions of IGF2 with IGFBPs, respectively) with obesity accompanying Type 2 Diabetes mellitus (T2DM) have been suggested [ 49 ]. The E-domain of the IGF2 protein, also known as preptin has been further associated with obesity [ 50 ] and T2DM [ 51 ].…”

Novel case of a scleroderma-mimicking syndrome associated with gastrointestinal stromal tumour

“…To our knowledge, this is the first reported case of GISTrelated scleroderma-like syndrome in the literature, making this a unique and valuable case. Rare cases of paraneoplastic syndromes associated with GIST have been reported: hypoglycaemia, [6][7][8][9][10] alopecia areata 11 and hypercalcaemia. 12 Samimi et al 13 described a case of GIST-related dermatomyositis.…”