Endocrine Abstracts

Background: The key physiologic defences against hypoglycaemia are the decrease in insulin and the increased secretion of glucose counterregulatory hormones, namely glucagon and epinephrine. The absence of warning signs of impending neuroglycopenia is known as hypoglycaemic unawareness.

Case report: Male, 26 year-old, without relevant medical history and with normal body mass index, presented with hypertension, palpitations and diaphoresis. Clinical suspicion of pheochromocytoma was confirmed by abdominal CT scan and 24-hour urinary catecholamine levels: normetanephrine 8304 μg/24 h (ref.88–444), norepinephrine 2511 μg/24 h (ref.15–80) and vanillylmandelic acid 33.5 mg/24 h (ref.1.4–6.5). He was diagnosed with bilateral pheochromocytoma and underwent bilateral adrenalectomy without perioperative complications (both benign tumours in anatomopathological study). Treatment with hydrocortisone and fludrocortisone was then initiated. Genetic testing revealed a missense mutation (arg167gln) at exon 3 of VHL gene compatible with Von Hippel-Lindau disease. His family history revealed pheochromocytoma in 3 members (mother, uncle and cousin), but genetic testing was not previously performed in any of them. Six years later the patient developed a pancreatic endocrine tumour of uncertain behaviour and was submitted to proximal pancreatectomy. De novo pancreatic lesions appeared 4 years later, leading to a total pancreatoduodenectomy. Post-operatively the clinical management of secondary diabetes was very difficult. He was treated with multiple daily insulin injection regimen (detemir twice daily plus prandial lispro). Given the absence of adrenal cortisol and catecholamines secretion, and of glucagon secretion by the pancreas, his hypoglycemic counterregulatory responses were impaired, leading to severe and recurrent hypoglycaemia unawareness. These episodes frequently had severe neuroglycopenic symptoms, seizures and loss of consciousness requiring glucagon or parenteral glucose therapy. Currently he is learning carbohydrate counting with symptoms improvement and use of an insulin pump was proposed.

Conclusion: This case report highlights the difficult and challenging management of hypoglycaemia unawareness in a patient with Von Hippel-Lindau disease previously submitted to bilateral adrenalectomy and total pancreatectomy.