A Case of Secretin-responsive Insulinoma with Low Serum C-peptide Levels

Abstract

Abstract. Insulinoma is the most common cause of fasting hypoglycemia resulting from autonomous insulin hypersecretion. A 59-year-old woman who had previously had an insulinoma and had undergone a partial pancreatectomy was admitted to our hospital because of recurrence of hypoglycemia after 27 years. She had two unusual endocrinological features: 1) the serum insulin response to intravenous secretin injection was not impaired, and 2) the serum C-peptide levels and ratios of serum C-peptide to insulin were relatively low. Two pancreatic tumors were readily detectable by computed tomography (CT) and magnetic resonance imaging (MRI). The selective arterial calcium injection (SACI) test showed a hyperinsulinemic response by calcium administration to the gastroduodenal artery. A partial pancreatectomy was done and her hypoglycemia disappeared. Histology revealed that the tumors were composed of monotonous, small round cells that were positive for both insulin and cathepsin B. As previous in vitro studies have shown that C-peptide can be metabolized within human insulinoma cells by proteolytic cleavage by cathepsin B, our patient's low serum C-peptide levels might have been caused by degradation of C-peptide by cathepsin B. According to the data from the literature, the molar ratio of serum C-peptide to insulin is generally decreased in patients with insulinoma than normal subjects. This case highlights the need for careful interpretation of C-peptide levels and the intravenous secretin injection test in the diagnosis of insulinoma.

Proinsulinoma causing severe hypoglycemia in a patient with type 1 diabetes mellitus

“…The C-peptide obtained at the same time was not as excessively elevated as expected given the insulin level 0.6 ng/ml (reference range is 0.8 ng/ml -3.1 ng/ml) but still inappropriately high for a glucose level of 64 mg/dl. Other insulinoma case reviews have reported lower C-peptide levels than would be expected [25,26] and possible explanations are that C-peptide can be rapidly degraded by cathepsin B in the islet tumor or not secreted into the serum [21] .…”

An unexpected revelation in a child with recurrent severe headaches

“…While in the ward, the patient continued to have recurrent hypoglycaemic episodes, despite eating well with a concurrent dextrose drip and no suggestion of exogenous insulin. An MRI pancreas, done to investigate for the rare but possible endogenous insulinoma with low C‐peptide, that results from degradation by tumour‐produced cathepsin B, was normal 2 . In view of that, despite no definite diagnosis, the boy was started on oral diazoxide, a benzothiadiazine derivative that increases blood glucose level by inhibiting pancreatic insulin release.…”

“…An MRI pancreas, done to investigate for the rare but possible endogenous insulinoma with low C-peptide, that results from degradation by tumour-produced cathepsin B, was normal. 2 In view of that, despite no definite diagnosis, the boy was started on oral diazoxide, a benzothiadiazine derivative that increases blood glucose level by inhibiting pancreatic insulin release. His mother was also taught capillary blood glucose monitoring and emergency intramuscular glucagon for severe hypoglycaemia.…”