Congenital hyperinsulinism clinical outcomes

The Congenital Hyperinsulinism Centre at Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH), is one of two Highly Specialised Services in the United Kingdom commissioned by NHS England, treating patients with congenital hyperinsulinism (CHI). The service has over 400 active patients and is a national and international referral centre. We have on average 40-50 new referrals per year, with 5-10 of these requiring extended inpatient stays of up to 6 months.

We have a dedicated multidisciplinary team to deliver the best care possible to these highly complex patients. Acute inpatients are predominantly cared for on Squirrel Ward (Endo/Met) and after discharge, patients are seen on Kingfisher ward if further investigations are required.

Combined with our clinical service we work closely with the Clinical Research team (CRF) to recruit patients onto clinical trials for new novel therapies in the treatment of CHI.

The GOSH CHI service is recognised as one of eight centres of international excellence, providing the highest level of multi-disciplinary care to CHI patients and their families, with an ongoing commitment to research and collaboration.

CHI is the most common cause of persistent hypoglycaemia in infancy. It is characterised by inappropriate and unregulated insulin secretion from the beta-cells of the pancreas. CHI causes the beta-cells to release insulin all the time and insulin secretion is not regulated by the blood glucose level (as occurs normally). The action of insulin causes hyperinsulinaemic hypoglycaemia. High insulin levels prevent ketone bodies being made. This means that the brain is not only deprived of its most important fuel (glucose), but also ketone bodies which are used as alternative fuels.

Secondary causes of hyperinsulinism can be subdivided into several categories including transient or persistent hyperinsulinism. These categories can often be distinguished by the length of treatment required and the infant’s response to medical management.

Transient hyperinsulinism means that increased insulin production is only present for a short duration and is found in conditions such as:

• Intrauterine growth retardation
• Infants of diabetic mothers
• Infants with perinatal asphyxia

Transient hyperinsulinism can occur in infants with no predisposing factors such as those listed above. Some of the transient forms of CHI need a medical treatment called Diazoxide, and the timeframe of this treatment ranges from weeks to months. Patients will be able to come off Diazoxide within their first year of life. A fasting tolerance test is performed when Diazoxide is stopped to ascertain if the CHI has completely resolved.

Before 2020 (pre-COVID 19) patients would remain on Diazoxide until they had been assessed in clinic an admission to GOSH arranged, which usually occurred around the 6-12 months of age. Parents would be advised to stop the Diazoxide at home three days before the admission. Patients would then be admitted to GOSH for two nights, for a 24-hour glucose profile and fasting tolerance test.

In 2020, COVID 19 restrictions delayed this admission. Consequently, patients remained on Diazoxide therapy, which has significant side effects, for longer than needed. Therefore, the CHI service developed a new pathway for parents/carers to safely stop the Diazoxide at home with close support from the CHI clinical nurse specialist (CNS) team.

The aim of the pathway was to reduce the amount of time a patient spent on Diazoxide. In 2021, when the CNS team became more confident in using this pathway there is a significant reduction in the duration of time patients were on the treatment, from an average of x days to y days. This reduced the risk of significant side effects e.g. pulmonary hypertension, fluid retention and hypertrichosis. Once off Diazoxide, patients no longer needed to be fluid restricted and could feed on demand.

The creation of the pathway meant we no longer had to wait for an admission date to GOSH before we stopped the Diazoxide. Patient stopped taking diazoxide several weeks/months before the admission for the fasting tolerance test to establish if the HI had resolved. Parents/carers regularly continued blood glucose monitoring during this time, replacing the need for a 24-hour glucose profile in hospital. The admission duration was halved from 48 hours to under 24 hours, to complete an age-appropriate overnight fasting tolerance test.

Reducing admission from two nights to one helps families by shortening hospital stays, which is especially helpful after long neonatal care. It eases travel for those coming from far away, lets parents return home sooner to care for other children, and lowers overall costs like travel and time off work.

In 2023, three years after establishing the pathway, we completed a service satisfaction survey, to obtain feedback from the families who had followed the CNS-led pathway and stopped the Diazoxide at home. We received 30 responses.

100% reported that the pathway for stopping Diazoxide at home was discussed with them, and subsequently 72% strongly agreed and 24% agreed that they felt confident stopping Diazoxide at home.

The CNS-led pathway outcomes have been shared with NHS England at the annual CHI UK audit meeting and with CHI specialist teams both nationally and internationally.

To support our commitment to continuous improvement, we will

1. Review outcome data from 2023 – 2024 to see if the average duration of Diazoxide therapy has further reduced and if the pathway can be further streamlined
2. Reduce hospital duration further by trialling, day case admission for fasting tolerance tests where appropriate.

This information was published in May 2025.