Background: Insulinomas are extremely rare tumors in children and an uncommon first manifestation of the MEN1 syndrome. An early clinical and genetic diagnosis is very important for the appropriate medical assessment and family counseling. In children, insulinomas are usually benign tumors with only a few reports of malignant cases.
Objective and hypotheses: To investigate clinical features, genetic and morphological characteristics of 12 children with primary pancreatic insulinomas.
Method: Insulinomas were diagnosed biochemically and by imaging and verified histopathologically. Detailed clinical and biochemical examination was performed in all children. Sequencing of the MEN1 gene was performed in 11 patients using bidirectional direct sequencing and MLPA deletion analysis. Follow up (mean age 16.6 years) included screening for signs of MEN1 (hormonal, imaging) and screening for metastases in case of malignant tumors.
Results: Twelve children aged 816 years were diagnosed to have primary pancreatic insulinoma. Seizures and weight gain were the most common symptoms of hyperinsuliaemic hypoglycemia (83.3 and 66.6% respectively). Five children (41.6%) had hypoglycemic coma before the diagnosis was established. Eight patients (66%) were erroneously diagnosed with epilepsy. Four out of 11 children investigated (36.3%) were found to have mutations in the MEN1 gene and developed hyperparathyroidism and hyperprolactinemia during the following 10 years. One patient with normal MEN1 analysis developed hyperparathyroidism. In the two patients with MEN1, relatives revealed the biochemical spectrum of MEN1 components, but with no clinical symptoms. Histopathological studies revealed G2 differentiation stage (ENETs grade) in five of 12 cases (41.6%), distant metastases were seen during follow up in two patients.
Conclusion: Late diagnosis of insulinoma is typical, probably due to unspecific symptoms and the disease rareness. MEN1 syndrome should be suspected in all cases of pediatric insulinomas, even in cases with no other clinical features of MEN1 and absence of suspicious family history. In our study a high incidence of malignant insulinomas was seen at follow up.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology