Prevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide

Diazoxide‐induced pulmonary hypertension in hyperinsulinaemic hypoglycaemia: Recommendations from a multicentre study in the United Kingdom

“…11,14 The strength of our study is our large, well-characterized cohort, including those with HH treated with diazoxide who did not develop PH. Thirteen patients (7%) in our cohort (n = 177) developed diazoxide-induced PH, which is similar to reported incidences of 2.4%-4.8%.…”

“…Pharmacotherapy for HH includes treatment with ATP-dependent potassium channel openers (diazoxide) and somatostatin analogues (octreotide and lanreotide). 11,13,14 However, these studies have merely noted the association of PH in patients with HH receiving diazoxide; they have not defined the cohort incidence of PH and have not consistently characterized risk factors associated with PH. It is structurally related to thiazide diuretics, but itself is a nondiuretic benzothiazine with an inhibitory effect on insulin secretion.…”

“…10 Diazoxide is usually well tolerated. Common adverse effects include hypertrichosis, fluid retention and electrolyte disturbances 11 ; however, less common side effects are ileus, coarsening of facies, neutropenia, hyperosmolar coma, gout and congestive cardiac failure. Following several case reports, the US Food and Drug Administration (FDA) issued a safety alert in September 2015 cautioning that pulmonary hypertension (PH) has been reported in 11 children treated with diazoxide.…”

“…12 Following this safety alert, several case reports and more recently two cohort studies have reported diazoxide-induced PH. 11,13,14 However, these studies have merely noted the association of PH in patients with HH receiving diazoxide; they have not defined the cohort incidence of PH and have not consistently characterized risk factors associated with PH. We aimed to collate information in a large national cohort to determine the incidence of diazoxide-related PH and test the association with likely risk factors.…”

“…withdrawal of diazoxide for PH resolution as dose reduction regimens were ineffective. Secondly, although we routinely performed baseline echocardiography prior to diazoxide initiation, echocardiography was not systemically performed afterwards unless clinically indicated so subclinical pulmonary hypertension may be missed.The pathophysiology of diazoxide-induced PH remains unclear.PH may occur due to off-target effects on SUR1 and SUR2 in pulmonary vasculature, similar to the Cantu syndrome, where SUR2 deficits are associated with pulmonary hypertension 11. The cause for persistence of PH is not known but suggests the possibility of other factors and predisposition to PH exacerbated by diazoxide.We acknowledge the limitations in our study in not being able to demonstrate a direct causal relationship between diazoxide and PH.…”