Clinically significant hypoglycaemia, in the absence of glucose lowering agents, is uncommon. Current guidelines recommend investigating hypoglycaemia only when Whipple’s triad is documented, i.e. symptoms and/or signs of hypoglycaemia, low measured plasma glucose and resolution of symptoms/signs after increasing the glucose concentration. (1)
We describe an unusual case of hypoglycaemia in a healthy asymptomatic 55-year-old man, who often drove 3h at a time for work and did not meet the requirements of the Whipple’s triad. An incidental low fasting plasma glucose concentration of 2.4 mmol/L led to further assessment in which morning plasma glucose measured twice was low (2.9-3.3 mmol/L) with insulin, proinsulin and c-peptide levels suggestive of a possible (pro)-insulinoma. Sulphonylurea screen was negative. As Whipple’s triad had not been documented, a 72 hour fast was undertaken which was terminated after only 12 hours due to hypoglycaemia (laboratory plasma glucose 2.4mmol/L), albeit asymptomatic. The corresponding plasma insulin (4.7 mU/ml), proinsulin (>99 pmol/L) and C-peptide (1.1 nmol/L) concentrations indicated a likely diagnosis of proinsulinoma. Endoscopic ultrasound (EUS) revealed a well circumscribed mass in the body of the pancreas and cytological analysis of a needle aspirate was in keeping with a neuroendocrine tumour. A subsequent Gallium-68 dotatate positron emission tomography demonstrated intense uptake in the region corresponding to the EUS lesion and a hypodense lesion, retrospectively seen, on a computed tomography scan (previously reported normal). The patient has been referred for surgical resection of this suspected proinsulinoma.
This interesting case highlights the challenges faced in diagnosis, when Whipple’s triad cannot be documented, and in management, when hypoglycaemia occurs in a completely asymptomatic person who drives for work. This case suggests a very insidious course in the development of hypoglycaemia that may be a feature of proinsulinomas. The case also underlines the utility of proinsulin levels when investigating for suspected insulinoma.