Medical Therapy in Patients With Endogenous Hypoglycaemia

Is Euglycemia Achievable?

Delphine Vezzosi; Eric Guillaume; Antoine Bennet; Céline Mouly; Hélène Hanaire; Philippe Caron


Clin Endocrinol. 2019;90(6):798-804. 

In This Article

Abtsract and Introduction


Context: While the only curative treatment for patients with endogenous hypoglycaemia related to inappropriate insulin or to insulin growth factor 2 (IGF2) secretion is surgery, medical treatment to normalize plasma glucose levels can be useful.

Objective: The aim of this prospective single centre study was to assess whether patients with endogenous hypoglycaemia, considered euglycaemic with medical treatments, experienced asymptomatic hypo- or hyperglycaemic excursions.

Patients and Methods: All patients with endogenous hypoglycaemia related to inappropriate insulin or to IGF2 secretion between 2012 and 2016 and considered normoglycaemic with medical treatment (absence of clinical hypoglycaemia and self-monitoring blood glucose in the normal range) were enroled and underwent a six-day continuous glucose monitoring (CGM) recording.

Results: Twenty-seven patients (inappropriate insulin secretion n = 25 and IGF2 secretion n = 2), treated with diazoxide (n = 16), somatostatin analogues (n = 7), glucocorticoids (n = 3) or a combination of these treatments (n = 1) were enroled. Twenty-five CGMs were analysed. CGM confirmed normoglycaemia in 11/25 patients (44%). Hypoglycaemias below 0.60 g/L were present in seven patients (28%) and were associated with hyperglycaemic excursions above 1.40 g/L in five patients. Seven patients (28%) had only hyperglycaemic excursions. Based on these results, treatment was modified in 14 patients (56%).

Conclusion: Despite the disappearance of hypoglycaemia-related clinical symptoms and normalization of blood glucose self-monitoring data, 56% of the patients with endogenous hypoglycaemia treated with medical therapy experienced asymptomatic hypo- and/or hyperglycaemia. Continuous glucose monitoring could be a useful approach to reveal and prevent hypo- or hyperglycaemic excursions.


Endogenous hypoglycaemias are rare in adults. Most of the cases are related to insulinoma, a neuroendocrine pancreatic tumour responsible for the excessive and uncontrolled secretion of insulin. More rarely, endogenous hypoglycaemia may be related to nesidioblastosis, non-islet-cell tumours secreting Insulin Growth Factor 2 (IGF2) or metabolic genetic disorders.

Surgery is currently the treatment of choice for insulinoma, as surgical resection achieves a cure in over 90% of patients.[1] However, surgery is not always feasible, particularly in metastatic unresectable insulinomas, diffuse nesidioblastosis, non-islet-cell tumour hypoglycaemia (NICTH) or in metabolic genetic disorders. In these cases, or in patients who remain uncured after surgery, medical treatment must be given in order to avoid potentially life-threatening hypoglycaemia.

The efficacy of medical treatment in patients with endogenous hypoglycaemia has been evaluated in a few studies.[2–6] However, the efficacy criteria for medical treatment required to restore euglycaemia were based on the disappearance of symptoms of hypoglycaemia and on self-monitoring of glucose levels, the frequency of which was never specified. Symptoms of hypoglycaemia may often be absent in patients with endogenous hypoglycaemia because highly frequent low plasma glucose levels are liable to lower the glycaemic threshold for clinical symptoms.[7] Moreover, it is difficult to perform blood glucose self-monitoring procedures several times a day during prolonged follow-up. Consequently, the real, overall efficacy of medical treatment in restoring normoglycaemia can be questioned in these studies.

Continuous glucose monitoring (CGM) is a valuable and useful tool in the management of diabetic patients as its use improves clinical outcomes.[8] Continuous glucose monitoring also appears useful in screening hypoglycaemia in patients with insulinoma.[9–11]

The aim of this prospective single centre study was to assess whether patients with hypoglycaemia related to inappropriate insulin or to IGF secretion and considered normoglycaemic (disappearance of clinical hypoglycaemia and normalisation of self-monitoring blood glucose) with medical treatments, had asymptomatic hypo- or hyperglycaemic excursions.