Case Report
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2020; 12(8): 519-524
Published online Aug 27, 2020. doi: 10.4254/wjh.v12.i8.519
Non-islet cell tumor hypoglycemia as an initial presentation of hepatocellular carcinoma coupled with end-stage liver cirrhosis: A case report and review of literature
Bo Yu, Rana Douli, Jose Amaya Suarez, Victor Perez Gutierrez, Mohammad Aldiabat, Maria Khan
Bo Yu, Rana Douli, Jose Amaya Suarez, Victor Perez Gutierrez, Mohammad Aldiabat, Maria Khan, Department of Medicine, Lincoln Medical Center, Bronx, NY 10451-5504, United States
Author contributions: Yu B wrote the manuscript; Douli R, Suarez JA reviewed the paper; Gutierrez VP edited the references; Aldiabat M and Khan M designed the figures.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Bo Yu, MD, MSc, Doctor, Department of Medicine, Lincoln Medical Center, 234 E.149th Street, Bronx, NY 10451-5504, United States.
Received: March 31, 2020
Peer-review started: March 31, 2020
First decision: July 5, 2020
Revised: July 8, 2020
Accepted: July 26, 2020
Article in press: July 26, 2020
Published online: August 27, 2020

Non-islet cell tumor hypoglycemia (NICTH) is a rare cause of persistent hypoglycemia seen in patients with hepatocellular carcinoma (HCC). It is likely to be underdiagnosed especially in the patients with poor hepatic function and malnutrition. Herein, we report a rare case of NICTH as the initial presentation of HCC in a patient with chronic hypoglycemia due to end-stage liver cirrhosis.


A 62-year-old male with chronic fasting hypoglycemia secondary to end-stage hepatitis C-related cirrhosis, presented with altered mental status and dizziness. He was found to have severe hypoglycemia refractory to glucose supplements. Imaging studies and biopsy discovered well differentiated HCC without metastasis. Further evaluation showed low insulin, C-peptide and beta-hydroxybutyrate along with a high insulin-like growth factor-2/insulin-like growth factor ratio, consistent with the diagnosis of NICTH. As patient was not a candidate for surgical resection or chemotherapy, he was started on prednisolone with some improvements in the glucose homeostasis, but soon decompensated after a superimposed hospital acquired pneumonia.


NICTH can occur as the sole initial presentation of HCC and is often difficult to correct without tumor removal. Clinicians should maintain high clinical suspicion for early recognition of paraneoplastic NICTH in patients at risk for HCC, even those with chronic fasting hypoglycemia in the setting of severe hepatic failure and malnutrition.

Keywords: Non-islet cell tumor hypoglycemia, Hepatocellular carcinoma, Liver cirrhosis, Insulin-like growth factor-2, Paraneoplastic syndrome, Case report

Core tip: Paraneoplastic Non-islet cell tumor hypoglycemia can occur as an initial presentation in patients with hepatocellular carcinoma and is often difficult to correct. It is tend to be underdiagnosed because patients often developed tolerance to chronic fasting hypoglycemia secondary to advanced liver cirrhosis. A ratio of insulin-like growth factor-2/insulin-like growth factor-1 above 10 is often found if non-islet cell tumor hypoglycemia is induced by overproduction of incompletely processed insulin-like growth factor-2. Oral corticosteroids and frequent high carbohydrate meals are often recommended but the outcome is unfavorable in general if tumor removal is not possible.