Endocrine Abstracts

Introduction: A rare cause of hypoglycemia is non-islet cell tumor hypoglycemia (NICTH), a paraneoplastic syndrome caused by tumoral overexpression of insulin-like growth factor 2 (IGF-2) and pro-IGF-2.

Case presentation: : A 57-year old woman presented with odd behavior each morning that improved after breakfast and extensive weight loss (13 kg in 3 years). The patient was hypoglycemic (2.6 mmol/l) with low insulin levels (<1.39 pmol/l) and C-peptide (0.089 nmol/l). Blood ketones were negative. She was eating normally and did not report alcohol consumption. Sulfonylurea screening was negative. Liver- and kidney function were normal. Further work-up revealed an enlarged liver with several focal lesions and multiple pulmonary nodules, suspicious for metastases. IGF-1 levels were immeasurably low. A liver biopsy revealed primary hepatocellular carcinoma. Due to the hypo-insulinemic non-ketotic hypoglycemia with immeasurably low IGF-1 levels, NICTH was suspected. IGF-2 was not tested due to the limited availability and the high cost at the patient’s expense. Therapy with octreotide and diazoxide was attempted but not successful. Therapy with dexamethasone elevated the glycaemia enough to be able to reduce the IV glucose infusions, but had to be tapered as quickly as possible due to initiation of immune therapy. Therefore, continuous glucose monitoring and pasireotide in compassionate use were initiated. Afterwards, she reported a subjectively better quality of life with fewer nightly hypoglycemic arousals. The dose of dexamethasone was reduced, the IV glucose was stopped and the patient was able to go home. Unfortunately, the patient was re-hospitalized after a few weeks due to progression of the malignancy under immune therapy.

Discussion: NICTH is a rare paraneoplastic syndrome caused by oversecretion of (immature) IGF-2 by benign or malignant tumors. IGF-2 can cause hypoglycemia due to insulin-like effects. In patients who fulfill the Whipple triad, other causes of hypoglycemia should be ruled out. NICTH should be suspected in a known or new diagnosis of malignancy with hypo-insulinemic non-ketotic hypoglycemia. If surgical resection, the mainstay of treatment for NICTH, is not feasible and an increase in frequency or volume of caloric intake isn’t enough, further drug therapy can be initiated. Different treatment strategies (glucagon infusions, glucocorticoids or recombinant human GH) are only feasible in the short-term and can have potential detrimental effects. Therapy with diazoxide or octreotide is not successful. Pasireotide has been attempted before in NICTH due to HCC with improved glycemic control. In our case, therapy with glucocorticoids was suboptimal considering her immune therapy. Pasireotide improved her quality of life.