Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants. Historically, clinicians have categorized this condition as either a focal lesion or a diffuse disease. However, a recent case series highlights the emergence of focal and diffuse hyperinsulinism occurring simultaneously in some patients. This discovery challenges the traditional binary classification. Furthermore, it necessitates a more nuanced approach to diagnosis and treatment for pediatric specialists.

Identifying Focal and Diffuse Hyperinsulinism in Clinical Practice

In the reported cases, three patients presented with diazoxide-unresponsive HI. Interestingly, their initial genetic testing was either negative or equivocal. To ensure that no surgically treatable lesions were missed, clinicians utilized 18-F-L 3,4-dihydroxyphenylalanine (18-F-DOPA) positron emission tomography (PET). This advanced imaging successfully identified focal pancreatic lesions in all three patients.

Following surgical resection, pancreatic biopsies revealed an unexpected finding. While the primary lesions were focal, the surrounding pancreatic tissue showed signs of diffuse disease. Specifically, pathologists identified rare islet cell nucleomegaly indicative of diffuse involvement. Consequently, subsequent fasting studies confirmed that the patients still had ongoing hyperinsulinism. This coexistence suggests that the underlying genetic mechanism involves complex hits to the pancreatic beta cells.

Impact on Treatment and Management Strategies

The management of focal and diffuse hyperinsulinism requires a multidisciplinary strategy. In these specific cases, removing the focal lesion provided a significant clinical advantage. Before surgery, the patients were unresponsive to diazoxide therapy. However, after the focal component was resected, the remaining diffuse disease became manageable with diazoxide.

This outcome is significant for clinicians because it demonstrates that surgery can be palliative even if it is not curative. By reducing the overall insulin-secreting load, clinicians can potentially avoid the need for near-total pancreatectomy. Therefore, careful postoperative evaluation and genetic correlation are essential for optimizing patient care in complex HI cases.

How can both focal and diffuse hyperinsulinism occur in the same patient?

This rare occurrence typically involves a complex genetic landscape. Often, a patient may have a germline mutation that predisposes them to diffuse disease, while a secondary somatic event in a specific area of the pancreas leads to the development of a focal lesion.

What role does 18-F-DOPA PET imaging play in these cases?

18-F-DOPA PET is crucial for identifying focal pancreatic lesions that may be amenable to surgical resection, even when genetic testing is equivocal or suggests diffuse involvement.

Can surgery cure a patient with both forms of the disease?

While surgical resection of the focal lesion may not completely cure the hyperinsulinism due to the underlying diffuse disease, it can significantly simplify medical management, often making the remaining condition responsive to diazoxide.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional relationship. Always seek the advice of a qualified healthcare provider for any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

• Sanders VR et al. Double trouble: When focal and diffuse hyperinsulinism occur simultaneously. Horm Res Paediatr. 2026 Mar 08. doi: 10.1159/000550909. PMID: 41795819.


• De León DD, et al. Clinical presentation and management of children with diffuse and focal hyperinsulinism: a review of 223 cases. J Clin Endocrinol Metab. 2013 Nov;98(11):E1786-91.


• Rahman SA, et al. The Heterogeneity of Focal Forms of Congenital Hyperinsulinism. Front Endocrinol (Lausanne). 2022;13:894645.