Endocrine Abstracts

Background: Congenital hyperinsulinism (CHI) is the result of unregulated insulin secretion from the pancreatic β-cells leading to severe hypoglycaemia.¹ Diazoxide is effective in virtually all forms of CHI except in those due to recessive (and some dominant) inactivating mutations in ABCC8 and KCNJ11 and in patients with focal CHI.² We report a case of CHI with acute kidney injury secondary to diazoxide.

Case presentation: A term male born to non-consanguineous Caucasian parents presented with hypoglycaemia on first day of life. Labetolol was administered during pregnancy for pre-eclampsia. The dopplers showed no end diastolic flow. He required up to 17 mg/kg per min of intravenous glucose. He had high insulin levels (26 mU/l) whilst hypoglycaemic (2.2 mmol/l). He was commenced on diazoxide and chlorothiazide. I.v. glucose was weaned off on day 8. On day 10, whilst on diazoxide, he had raised creatinine of 153 μmol/l. His blood pressure, urine output and weight remained satisfactory. There was no microscopic haematuria. Renal ultrasound scan was normal. Chlorothiazide was discontinued and diazoxide weaned off over the next 4 days. He maintained stable glucose levels and renal function improved following this intervention.

Discussion: Diazoxide is an antihypertensive antidiuretic benzothiadiazine. It acts on the pancreatic β-cells inhibiting insulin secretion. Tolerance to diazoxide is usually good. Renal side effects are rarely described. Diazoxide is also an arterial vasodilator, and in combination with diuretics, can induce acute changes in renal function with associated tubular sodium avidity (http://www.nature.com/nrneph/journal/v2/n2/full/ncpneph0076.html). Reported renal side effects of diazoxide include azotemia, decreased creatinine clearance, reversible nephritic syndrome and haematuria.

Conclusion: Raised creatinine can occur as a side effect of diazoxide. The half-life in children is 9–24 h and increases in patients with renal impairment (http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1432880278807.pdf). This case highlights the importance of regular monitoring of renal function in patients with CHI on diazoxide.

References: 1. Senniappan S, Arya VB & Hussain K. The molecular mechanisms, diagnosis and management of congenital hyperinsulinism. Indian J Endocrinol Metab 2013 17(1) 19–30 (doi: 10.4103/2230-8210.107822).

2. Arnoux JB, Verkarre V, Saint-Martin C, Montravers F, Brassier A, Valayannopoulos V, Brunelle F, Fournet JC, Robert JJ, Aigrain Y et al. Congenital hyperinsulinism: current trends in diagnosis and therapy. Orphanet J Rare Dis 2011 6 63 (doi: 10.1186/1750-1172-6-63).