Metastatic Insulinoma in a 16-Year-Old Adolescent Male With Men-1: A Case Report and Review of the Literature

Abstract

Objective: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant condition associated with various combinations of endocrine and nonendocrine tumors. Insulinomas are rare endocrine tumors in the pediatric age group and may be associated with MEN-1 in 10% of cases. Malignant insulinomas only constitute 5 to 10% of all the insulinomas and are exceedingly rare in children. There are only 11 cases of malignant insulinoma reported in the literature in the pediatric age group. Methods: We are reporting a 16-year-old adolescent male who presented with symptoms of hypoglycemia for the 4 months prior to referral. Results: He was diagnosed with malignant insulinoma with multiple metastases to liver and was treated with surgical resection followed by octreotide treatment. He had additional findings consistent with the diagnosis of MEN-1, including elevated prolactin levels combined with a 4 to 5 mm pituitary lesion possibly due to prolactinoma and mildly elevated calcium levels with a parathyroid ultrasound demonstrating a parathyroid adenoma on the left side measuring 8 × 6 × 4 mm in diameter. He has been free of symptoms and radiologic findings of recurrence of insulinoma 1-year post surgery. Conclusion: Malignant insulinoma is extremely rare in children, but should be considered in cases of hyperinsulinemic hypoglycemia. MEN-1 should also be considered because insulinoma may be the first finding of MEN-1. Surgical resection is the treatment of choice. Somatostatin analog is a safe and effective treatment in children in cases with metastatic insulinoma when residual tumor is present.

Insulinoma masquerading as a loss of consciousness in a teenage girl: case report and literature review

“…We performed a thorough literature review and found less than one hundred pediatric insulinoma cases were reported since 1960 [ 8 – 30 ] (Table 1 ), of which three children had malignant insulinoma [ 9 , 22 , 26 ]. Presentation varied from subtle and non- specific to catastrophic events.…”

“…The spectrum of symptoms included confusion, palpitation, sweating, tremors, hunger, irritability, dizziness, drowsiness, generalized weakness, abdominal pain, psychomotor slowing, syncope and seizures. Most of the episodes occurred during the morning hours, after exercise or fasting, and resolved after food or juice intake [ 9 , 10 , 14 , 15 , 17 – 19 , 27 ]. Eighteen children experienced seizure activity [ 13 , 14 , 16 , 18 – 21 , 23 – 25 , 27 , 29 , 30 ], four children were found in a comatose state [ 29 , 30 ], three children had mental retardation as sequelae after surgery [ 11 , 27 , 30 ] and two children died [ 22 , 30 ].…”

“…AN is thought to be caused by proliferation of fibroblasts and keratinocytes when excess insulin binds to insulin like growth factor-1 receptors [ 34 ]. This would lead one to believe that all cases of hyperinsulinism would be associated with AN; however, not all insulinomas present with AN [ 9 , 10 ]. Why AN is present in some and not in others is not clear.…”

Insulinoma in childhood: a retrospective review of 22 patients from one referral centre

“…Apart from the MEN1 gene, only few genes are known to cause insulinoma (14,16). Very few reports in the literature describe the association of insulinoma with neurofibromatosis 1 and tuberous sclerosis (3)(4)(5). In our cohort, children did not present with any specific clinical features but hypoglycemia and, therefore, were tested for the MEN1 mutations only.…”

“…In the pediatric population, insulinomas are even more rare. Most of the reports in the literature describe single pediatric clinical cases (3)(4)(5)(6)(7)(8)(9)(10)(11). There are only few pediatric cohorts of 9-10 cases reported (12,13).…”