|Year : 2022 | Volume
| Issue : 4 | Page : 276-279
Non-islet cell tumor-related hypoglycemia in a case of metastatic gastrointestinal stromal tumor: A rare paraneoplastic syndrome: A case report
Nalini Kanta Ghosh1, Ashok Kumar1, Vijay Kumar Sharma1, Vikrant Verma2
1 Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Submission||25-Apr-2022|
|Date of Decision||28-Sep-2022|
|Date of Acceptance||30-Sep-2022|
|Date of Web Publication||17-Nov-2022|
Dr. Nalini Kanta Ghosh
Department Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Clinical presentations depend upon the site of involvement. It can lead to obstruction, bleeding, perforation, or symptoms due to mass effects. Tumor-induced hypoglycemia (nonislet cell tumor-related hypoglycemia [NICTH]) is a rare manifestation of GIST. Case Report: We herewith present the case of a 46-year-old female who presented with multiple abdominal lumps and recurrent episodes of syncope due to NICTH. On investigations, she was diagnosed to have unresectable GIST on biopsy. Her hypoglycemic episodes could be explained by rare paraneoplastic syndrome due to the raised levels of insulin-like growth factor-2. After treatment with imatinib (800 mg once daily), her hypoglycemic episodes subsided, which supported the diagnosis. Conclusion: NICTH is a rare paraneoplastic manifestation of GIST; targeted therapy can avert neuroglycopenic symptoms.
Keywords: Imatinib, metastatic gastrointestinal stromal tumor, nonislet cell tumor-related hypoglycemia
|How to cite this article:|
Ghosh NK, Kumar A, Sharma VK, Verma V. Non-islet cell tumor-related hypoglycemia in a case of metastatic gastrointestinal stromal tumor: A rare paraneoplastic syndrome: A case report. Apollo Med 2022;19:276-9
|How to cite this URL:|
Ghosh NK, Kumar A, Sharma VK, Verma V. Non-islet cell tumor-related hypoglycemia in a case of metastatic gastrointestinal stromal tumor: A rare paraneoplastic syndrome: A case report. Apollo Med [serial online] 2022 [cited 2023 Feb 3];19:276-9. Available from: https://apollomedicine.org/text.asp?2022/19/4/276/361433
| Introduction|| |
Gastrointestinal stromal tumor (GIST) is the most common type of mesenchymal tumor of the gastrointestinal (GI) tract. Usual presentations include intestinal obstruction, bleeding, and perforation. Rare presentations are paraneoplastic symptoms such as hyperpigmentation, mastocytosis, and hypoglycemia. Hypoglycemia is rarely observed in GIST, known as nonislet cell tumor-related hypoglycemia (NICTH). NICTH mimics insulinoma, and diagnosis is suspected in the presence of a bulky or metastatic tumor, biochemical evidence of low insulin, C-peptide, and elevated insulin-like growth factor-2 (IGF-2). The goals of the treatment include management of hypoglycemia and modalities to decrease the tumor burden. There are only 10 case reports in the literature on NICTH in GIST [Table 1]. We present a rare case of metastatic GIST, where the patient presented with hypoglycemic episodes and was managed with Imatinib.
|Table 1: Case reports reporting hypoglycemia in gastrointestinal stromal tumor|
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| Case Report|| |
A 46-year-old female presented with complaints of diffuse abdominal pain for 2 months, which was insidious in onset, mild, and dull aching associated with abdominal distention and constipation. She had no nausea, vomiting, jaundice, GI bleeding, anorexia, or weight loss. History of seizure, bone pain, or respiratory distress was absent. She had intermittent episodes of syncope, which used to improve after food intake. Examination revealed multiple, nontender, firm, mobile lumps over the abdomen. Rectal examination, per-vaginal examination, and other systemic examinations were within normal limits. Abdominal sonography and contrast-enhanced computed tomography revealed multiple heterogeneously enhancing lesions in the peritoneal cavity, mild ascites, and subcentimetric lymph nodes in the external iliac, obturator, and common iliac region [Figure 1]. Percutaneous biopsy and immunohistochemistry revealed a spindle cell tumor positive for CD117 and DOG1. It was negative for desmin. There were 1–2 mitotic figures per 50 high-power fields, and the Ki-67 proliferation index was 2%–3% [Figure 2]. Hematological and biochemical parameters were normal. She had multiple hypoglycemic episodes. Blood sample collected during the episode of hypoglycemia revealed serum glucose level to be 36 mg/dl, blood ketones 0.5 mmol/l (≤0.5 mmol/l), insulin levels <1.39 pmol/l (17.8–173 pmol/l), C-peptide 0.026 nmol/l (0.37–1.47 nmol/l), growth hormone 0.542 ng/ml (0.4–10 ng/ml), and serum cortisol 1059 nmol/l (138–550 nmol/l) which ruled out hyperinsulinism or adrenal insufficiency. NICTH is usually diagnosed based on evidence of tumor and hypoglycemia after ruling out other possible etiologies. Thus, a clinical diagnosis of NICTH was made in this patient. Serum levels of IGF-2 could not be estimated due to limited laboratory facility. She was advised a high dose (800 mg) of imatinib based on previously reported cases. In the first 24 h of treatment, there were no hypoglycemic episodes [Figure 3]. Hence, the diagnosis of GIST-induced hypoglycemia was ascertained. The further plan was to continue imatinib and assess response. The patient remained euglycemic for 4 weeks; however, she succumbed to her illness.
|Figure 1: CECT shows multiple heterogeneously enhancing lesions in the peritoneal cavity. CECT: Contrast-enhanced computed tomography|
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|Figure 2: Histopathology slides of GIST with markers. (a) An intersecting fascicle of plump spindled tumor cells, ×100. (b) Tumor cells, ×400. (c) Tumor cells, ×1000. (d) Vimentin. (e) CD117. (f) DOG1. (g) No staining for Desmin. (h) Ki-67 index (2%–3%). GIST: Gastrointestinal stromal tumor|
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| Discussion|| |
Hypoglycemia(NICTH) is a rare presentation of GIST, which is due to increased secretion of IGF-2., A few case reports and small series were published in the literature [Table 1]. The incidence of NICTH is 2.1–15 per million people, and there is no gender preference., It is usually observed in bulky or metastatic tumors of the mesenchymal origin (fibrosarcomas, mesotheliomas, leiomyosarcomas, and hemangiopericytomas) and rarely observed in carcinoid tumors, myelomas, lymphomas, hepatocellular carcinomas, and colorectal cancers.,,, Hypoglycemia in NICTH results from suppressed growth hormone secretion and increased synthesis of incompletely processed IGF-2. IGF-2 stimulates the insulin receptors, improves glucose utilization by skeletal muscles, and simultaneously inhibits glucose release from the liver resulting in hypoglycemia. Daughaday first reported a case of NICTH in association with fibrosarcoma. There are no published guidelines for the diagnosis of this rare entity. Usually, the clinical diagnosis of NICTH is made when a patient has a tumor detected on imaging, confirmed by histological examination, and all other hypoglycemia causes have been ruled out. In our patient, insulin hypersecretion, growth hormone, or cortisol deficiency were ruled out based on biochemical parameters. Serum IGF-2 is generally elevated in these cases; however, diagnosis can also be made based only on clinical suspicion (Singhal et al.), like in our case. Usually, these patients have decreased levels of GH, IGF-1, and increased IGF-2/IGF-1 ratio (>10). Treatment of NICTH includes correction of hypoglycemia and measures to reduce the tumor burden. Tumor-targeted treatment measures include local (selective embolization or radiofrequency ablation) or systemic therapies (chemotherapy). Palliation of symptomatic hypoglycemia is the primary therapeutic goal as it can be lethal; however, the long-term outcome depends upon the response of the tumor to the therapy. Most of these patients have unresectable or metastatic disease at the time of diagnosis, and R0 resection is challenging. Hence, a local tumor ablation therapy or systemic chemotherapy is preferred. Hypoglycemic epsodes are relieved with exogenous glucose, stimulation of glycogenolysis, or gluconeogenesis and the drugs used are glucagon, diazoxide, octreotide, recombinant growth hormone, and glucocorticoids.
GIST is a chemotherapy- and radiotherapy-resistant tumor. It responds to tyrosine kinase inhibitors (TKIs) (e.g., imatinib, sunitinib, and regorafenib). Hypoglycemia induced by GIST responds to TKIs, low-dose steroids, and growth hormones., Some reports suggest that high doses of imatinib can abate hypoglycemic episodes. In our patient, high doses of imatinib (800 mg/day) made her euglycemic. TKIs decrease glucose uptake by tumor cells and relocate the glucose receptors inside the cell resulting in a euglycemic state. Most patients have metastatic disease, and information is limited regarding guidelines for the management and long-term follow-up of such patients. Our patient had metastatic GIST with hypoglycemia and responded to imatinib; however, she succumbed to her illness, probably attributed to metastatic disease. This patient could have been evaluated with mutational analysis and PET scan for formulating a better therapeutic plan, but due to financial constraints, it could not be performed.
| Conclusion|| |
NICTH is a rare clinical presentation in association with GIST. Tumor-directed treatment, i.e., surgery or targeted therapy, can decrease tumor burden and improve glycemic status; however, the prognosis is poor. Thus, the awareness of such a rare clinical presentation can suggest advanced disease and dictate further management.
Conflicts of interest
There are no conflicts of interest.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
NKG and AK – Concept, design, manuscript writing and critical analysis, and final proofreading. VKS and VV – manuscript writing, information collection, and critical analysis.
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[Figure 1], [Figure 2], [Figure 3]