Hypoglycemia As Initial Manifestation Of Hepatocellular Carcinoma In A Patient With Diabetes

Document Type

Article

Abstract

Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a known but rare paraneoplastic syndrome associated with tumors of epithelial and mesenchymal origin. It is reported in 4-27% of patients with hepatocellular carcinoma (HCC) and is associated with poor prognosis. Here we present a case of hypoglycemia as the initial manifestation of malignancy in a patient with diabetes.

Case: A 69 year old male with a history of type 2 diabetes mellitus presented due to confusion and diaphoresis, with blood glucose in the 20s on EMS arrival and improvement in mental status after dextrose administration. He had multiple ED visits due to hypoglycemia over the prior 3 months and his antidiabetic agents had been discontinued. Hepatomegaly was noted on physical exam. CT abdomen and pelvis and abdominal MRI demonstrated multiple hepatic lesions concerning for malignancy and liver biopsy confirmed HCC. Fasting protocol was initiated and labs obtained during a hypoglycemic episode. Insulin was 0.14 uIU/mL (Reference range (RR) 2.6-24.9uIU/mL); C-peptide 0.4 ng/mL (RR 1.1-4.4 ng/mL) ; Proinsulin 1.2 pmol/L (RR 0.0-10/0pmol/L); Random and A.M. cortisol were normal and sulfonylurea screen and was negative - findings consistent with non-insulin dependent hypoglycemia. Further workup showed IGF-1 of 17 ng/mL (RR 59-230 ng/mL), IGF-2 of 515 ng/mL (RR 333-967 ng/mL), and IGFBP-2 of 1467 ng/mL (RR 151-740 ng/mL), with IGF-2: IGF-1 ratio of 30.3 confirming the diagnosis of NICTH. The patient was not a surgical candidate and treated with 10% dextrose infusion, dietary intervention, Prednisone and Octreotide. He was discharged after stabilization of serum glucose, and readmitted 2 weeks later due to pneumonia, AKI and refractory hypoglycemia. Embolization was performed by IR with devascularization of 80% of tumor parenchyma. His clinical status continued to decline, and he ultimately elected comfort-directed care and expired.

Discussion: NICTH is a rare but serious paraneoplastic syndrome associated with significant morbidity and mortality. Proposed mechanisms include increased production of IGF-2 or pro-IGF-2 (known as “big IGF-2”) leading to stimulation of the insulin receptor, high tumor burden in the liver leading to impairment of gluconeogenesis or increased glucose consumption, and infiltration of the adrenals with resultant adrenal insufficiency. An IGF-2:IGF-1 ratio more than 10 confirms the diagnosis in IGF-2 producing neoplasms. Treatment focuses on surgical removal or debulking with chemo- and/or radiation therapy, and embolization. Glucocorticoids are a mainstay in medical management, with case reports describing the use of somatostatin analogs, glucagon, and growth hormone. Diagnostic delays can occur, particularly in patients with diabetes taking multiple glucose-lowering medications, which highlights the importance of a systematic approach to the hypoglycemic patient.

First Page

bvae163.799

DOI

10.1210/jendso/bvae163.799

Publication Date

10-2024

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