Infants with congential persistent hyperinsulinism have been treated for years with diazoxide, well before many of the genetic mutations underlying the condition were known (there are now at least 14 of them!). Diazoxide seems to be relatively well tolerated in this group of patients, although they do not all respond; they are otherwise difficult to treat, and may eventually need other interventions.

There seems to be an increasing use of diazoxide among infants with transient hyperinsulinism also, several recent large cohorts have been published, and there are increasing reports of adverse secondary events. The most common serious event is pulmonary hypertension, which seems to be more common in this group than with genetic congenital hyperinsulinism. (Thornton P, et al. Rate of Serious Adverse Events Associated with Diazoxide Treatment of Patients with Hyperinsulinism. Horm Res Paediatr. 2019;91(1):25-32.) That study showed an 8% incidence of pulmonary hypertension in the stress-hyperinsulinism group and a 1% incidence with genetic hyperinsulinism.  Fluid retention is also frequent, and a case of profound persistent hypotension leading to PVL in a preterm baby has been reported (it was first used as an anti-hypertensive agent that was accidentally noticed to cause hyperglycemia). In rats it dilates the ductus arteriosus.

In the largest cohort study of over 1000 treated babies, 12% of babies needed new oxygen support after treatment was started, 5% had to be intubated and 14% were started on diuretics. In other reports babies have become extremely unwell with right vetricular failure due to pulmonary hypertension. In that same cohort 92% of the babies were weaned off diazoxide before discharge from the hospital, which makes me wonder if they really needed it.

Many babies with so-called perinatal stress hypoglycemia can be easily managed with extra glucose, but for some their course is prolonged and complex; In some of those babies it may be that diazoxide is a reasonable solution, but right now it is impossible to calculate the balance of benefits and risks. I wonder if the current increase in use is really justifiable with a medication that has these toxicities, we really need much better studies. It is a common enough problem that children with ‘perinatal stress hyperinsulinism’ that persists could be randomized, perhaps after 5 days or so when the risk seems to be less, and to avoid use in teh preterm or in infants with respiratory distress as they seem to have higher risks. (Herrera A, et al. Prevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide. J Clin Endocrinol Metab. 2018;103(12):4365-72)