Treatment advances translate to better congenital hyperinsulinism outcomes

medwireNews: Faster diagnosis and use of individualised treatments for congenital hyperinsulinism (CHI) has led to major improvements in neurological and endocrine outcomes over time, say Finnish researchers.

Jonna Männistö (Kuopio University Hospital, Finland) and colleagues base their conclusions on data from 106 patients with persistent CHI and 132 with transient CHI who were diagnosed between 1972 and 2015. The team notes that CHI diagnoses would be unlikely outside the 19 large hospitals whose records they searched, making their study cohort “representative for Finland”.

Treatment changes in the persistent CHI group over time included a shorter duration of intravenous glucose treatment from the year 2000 compared with previously, at 8 versus 22 days. In parallel, the time between first hypoglycaemia and initiation of hyperinsulinaemic medication (diazoxide or octreotide) was significantly shorter in recent years, at 6 versus 19 days.

Prior to 2000, 51.4% of patients with persistent CHI underwent a near-total pancreatectomy of 90% or greater for presumed diffuse CHI, whereas just 2.7% had a partial resection all of which occurred in the 1990s. Partial resection was significantly more common from 2000, with 17.4% of patients undergoing this treatment. No patient had a near-total pancreatectomy after 1996, but the researchers say this was partly because no patient in this period had mutations affecting both copies of the gene encoding the KATP channel.

Outcomes were good overall, with 69.8% of the persistent CHI and 79.5% of the transient CHI group exhibiting normal development. But a corresponding 20.8% and 15.9% had mild developmental difficulties, and 8.5% and 4.5% had intellectual disability.

However, in patients with persistent CHI, rates of these adverse outcomes were markedly lower from 2000, coming into line with rates for the transient CHI patients. Specifically, mild developmental difficulties were seen in just 13.0% of those diagnosed from 2000, compared with 35.1% of those diagnosed in earlier years. The corresponding rates for intellectual disability were 5.8% versus 16.2%.

The researchers concede that the absence of the “most severe phenotypes” may be partly responsible for the good outcomes in patients treated since 2000, but they believe that “increased detection of hypoglycemia before symptoms (by the advanced routine blood glucose screening in newborns at risk), as well as earlier diagnosis of hyperinsulinism and achievement of normoglycemia” are also important factors underlying the improvements over time.

Of note, no patient with isolated persistent CHI or isolated transient CHI diagnosed from 2000 had intellectual disability, and rates of adverse neurological outcomes were higher overall for children with comorbidities that potentially affected neurodevelopment.

“Interestingly, the prevalence of Down syndrome was surprisingly high, although it has not been previously reported to associate with hyperinsulinism”, write the researchers in The Journal of Clinical Endocrinology & Metabolism.

It was present in 2.1% of the cohort, giving a rate of one in 50 compared with one in 870 for the general Finnish population.

Epilepsy occurred in 5.8% of the persistent CHI patients diagnosed from 2000, in 32.4% of those diagnosed earlier, and in 3.0% of the transient CHI group (0.0% of those with isolated CHI).

Diabetes occurred in 43.2% of the patients with persistent CHI treated before 2000 and clinical pancreatic exocrine dysfunction was reported for 29.7%; these rates fell to 0.0% and 4.3%, respectively, for patients treated more recently.

These improvements occurred because “all the diazoxide-unresponsive patients avoided near-total pancreatectomy due to having focal CHI or adequate response to octreotide”, say Männistö and team.

Of note, 68% of the 74 patients who received medical treatment (rather than surgery) for persistent CHI were able to discontinue their medication.

This rate, which the researchers say is in line with previous reports, indicates “a high probability of spontaneous remission of drug-responsive CHI, occurring most often before school age, but sometimes even in adulthood.”

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

J Clin Endocrinol Metab 2021; doi:10.1210/clinem/dgab024
Martin Savage
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