Endocrine Abstracts

Introduction: Insulinoma is a rare neuroendocrine tumour of the pancreas. Its resection is the only curative treatment. However, medical therapy may be needed to prevent severe preoperative hypoglycaemia, when surgery is contraindicated, delayed or refused and in case of unresectable metastatic disease. To our knowledge, a comparison between these two medications has never been performed.

Case report: We describe the case of a 27-year-old patient without specific past history who was referred for discomfort suggestive of hypoglycaemia. A diagnosis of insulinoma was made in April 2018 after a fasting test. The patient had a symptomatic hypoglycaemia after 12 hours with a blood glucose at 33 mg/dl, an insulin level at 74.8 pmol/l, a c-peptide at 1.38 pmol/ml and B-hydroxybutyrate at 0.102 mmol/l. We did not detect sulfonylurea in the 24-hour urine collection. Pancreatic magnetic resonance imaging confirmed a 17×20 mm lesion in the upper part of the pancreatic body, that was also visualized by indium-111 pentetreotide scintigraphy (OctreoScan). We therefore scheduled an operation that was possible 6 weeks later. Diazoxide treatment was then initiated at a dose of 50 mg three times a day which was gradually increased to 150 mg three times a day. On this treatment, the patient kept symptomatic hypoglycaemia twice a week. In addition, he had increasing dyspnoea. A cardiopulmonary assessment, including a chest radiograph, a spirometry and cardiac ultrasound, was normal. We assumed that dyspnoea could be favoured by water retention caused by diazoxide. So, after a month on diazoxide, the patient was admitted to hospital to shift treatment to lanreotide 120 mg under glucose monitoring. Thereafter, the patient did not experience hypoglycaemia and dyspnoea disappeared until operation. An EORTC Quality of Life Questionnaire-Core 30 (version 3.0) was filled in by the patient, without treatment, under diazoxide 450 mg a day, lanreotide 120 mg and a month after surgery. Summary scores were respectively 84.7, 73.3, 90.9 and 99.1. The operation, consisting in an enucleation was uneventful.

Conclusion: In our patient, diazoxide failed to demonstrate its effectiveness at the maximum tolerated dose and at the cost of side effects decreasing the quality of life. Studies have already demonstrated the presence of these side effects such as that of Gill et al. who tested diazoxide in 40 patients. 1) Forty-seven percent had side effects, mainly sodium-water retention and hirsutism for a total effectiveness rate of 59%. Cases of heart failure have also been reported under diazoxide. 2) Regarding somatostatin analogues, there are few reports available. A prospective study including 21 patients showed efficacy of octreotide in 67% of cases with a good tolerance. 3) OctreoScan does not seem to be a predictor of response to this treatment. In conclusion, if medical treatment is required, somatostatin analogues rather than diazoxide may be an effective and well-tolerated option in insulinoma.

References

1. Gill G.V., Rauf O., MacFarlane I.A. Diazoxide treatment for insulinoma: a national UK survey, Postgrad Med J. 1997; 73:640–1.

2. Komatsu Y., Nakamura A., Takihata M., Inoue Y., Yahagi S., Tajima K., Tsuchiya H., Takano T., Yamakawa T., Yoshida M., Miyoshi H., Terauchi Y. Safety and tolerability of diazoxide in Japanese patients with hyperinsulinemic hypoglycemia. Endocr J. 2016; 63:311–4.

3. Vezzosi D., Bennet A., Courbon F., Caron P. Short- and long-term somatostatin analogue treatment in patients with hypoglycaemia related to endogenous hyperinsulinism. Clin Endocrinol (Oxf). 2008; 68:904–11.