Case: A 79 years old frail lady with history of dementia and hypertension presented with refractory hypoglycaemia over a period of 3 months requiring multiple admissions. During her most recent admission, she required continuous dextrose infusion to maintain euglycaemia. The severe spontaneous hypoglycaemia in this non-diabetic lady, warranted a series of investigations. TFT and Short Synacthen Test excluded thyroid dysfunction and hypoadrenalism. The anterior pituitary profile including prolactin, LH, and FSH were all normal. Two separate samples of IGF-I was 8 nmol/L and 6.6 nmol/L (1025 nmol/L). CT scan with contrast of the abdomen and pelvis revealed a heterogeneously enhancing mass (6.6 cm) arising from the lower pole of the left kidney consistent with renal cell carcinoma. Concomitantly there were extensive peripherally enhancing heterogeneous mass lesions in the liver, the largest measuring at 12 cm. The pancreas was normal. IGF-II:IGF-I ratio during the event of hypoglycaemia (blood glucose 1.6 mmol/L) was less than 10, which was inconsistent with non-islet cell tumour induced hypoglycaemia (NICTH). Inappropriate elevation of C-peptide 4210 pmol/L (174960 pmol/L) and Proinsulin >200 (07 pmol/L) was noted, along with a suppressed Insulin at 12 pmol/L (0180).
In view of multiple comorbidities, a palliative approach was taken. The post-mortem confirmed a clear cell renal carcinoma of the left kidney. Unexpectedly, the morphology and immunoprofile of the liver metastases were consistent with proinsulin secreting neuroendocrine tumour. The immunostaining showed focal strong insulin immunoreactivity, as well as widespread CD56, synaptophysin, and chromogranin A, with negative staining for RCC.
Discussion: Proinsulinoma is a rare condition and can be masked by concomitant metastatic malignancy. Multiple hepatic metastases is a well-known cause of spontaneous hypoglycaemia. However, in severe intractable hypoglycaemia, coexistence of insulin secreting tumour needs to be considered to avoid missing them.