Refractory hypoglycemia in a pediatric patient with desmoplastic small round cell tumor

Abstract

Background Tumor-induced hypoglycemia is a rare and serious complication that is usually a consequence of either excessive insulin secretion (insulinoma) or because of non-islet cell tumor hypoglycemia (NICTH). NICTH is a rare phenomenon seen most often in adult patients. It is associated with different tumor types. Here, we report the first case to the best of our knowledge in the literature of a pediatric patient with NICTH associated with desmoplastic small round cell tumor (DSRT). Case presentation This is a 15-year-old girl who presented with symptomatic hypoglycemia and abdominal mass. She required an intravenous glucose infusion rate as high as 9 mg/kg/min in addition to glucose containing oral supplements in order to maintain her blood glucose above 60 mg/dL. Computed tomography (CT) scan of the chest, abdomen and pelvis showed multiple hepatic lesions with an intraperitoneal soft tissue mass which subsequently was diagnosed as DSRT. When the blood glucose was 45 mg/dL, the insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels were suppressed with an appropriate elevation of cortisol. Subsequently, an insulin-like growth factor-2 (IGF-2) level was sent and the IGF-2:IGF-1 ratio was found to be elevated >10 consistent with NICTH. After the first dose of chemotherapy, hypoglycemia improved, and she was weaned off glucose containing fluids. Conclusions NICTH should be considered in all cancer patients regardless of their age with refractory hypoglycemia.

Non-islet Cell Tumor-induced Hypoinsulinemic Hypoglycemia in the Setting of Metastatic Desmoplastic Round Cell Tumor

“…A ratio greater than 10 is considered to be pathognomonic of IGF-II mediated NICTH. The implicated tumors include hepatocellular carcinoma, gastric carcinoma, solitary fibrous pleural tumor of the lung, desmoplastic small round cell tumor, mesothelioma and leiomyosarcoma, among a few others [2-3,5].…”

“…If this is not possible, then continuous infusions of intravenous dextrose may be used. For long-term management using corticosteroids, growth hormone, and glucagon, either individually or in various combinations, is recommended for maintenance of euglycemia [1-3, 5].…”

Unraveling the IGF System Interactome in Sarcomas Exploits Novel Therapeutic Options

“…Among other components of the IGF system, two different case reports described abnormal IGF2 secretion in serum of two patients affected by desmoplastic small round cell tumor [201,202]. In those patients, IGF2 levels were associated with tumor hypoglycemia [201,202]. Recent RNAseq confirmed the strong over expression of IGF2 across desmoplastic small round cell tumors and ChIP seq analyses demonstrated that EWS-WT1 direclty targets IGF2, contributing to its over expression [203].…”

“…Published data indicate that EWS-WT1-mediated upregulation of IGF1R leads to enhanced ligand/receptor interaction and growth stimulation [71,200]. Among other components of the IGF system, two different case reports described abnormal IGF2 secretion in serum of two patients affected by desmoplastic small round cell tumor [201,202]. In those patients, IGF2 levels were associated with tumor hypoglycemia [201,202].…”

Immunotherapy and Radioimmunotherapy for Desmoplastic Small Round Cell Tumor

“…Another target of EWS-WT1 is IGF-1R, a tyrosine kinase receptor that is frequently upregulated in cancer cells, leading to dysregulation of the IGF pathway (30). There are several reports of DSRCT patients presenting with severe hypoglycemia as a result of an elevated IGF-II : IGF-I ratio, a consequence of IGF pathway dysregulation (31,32)…”