Background Pediatric pheochromocytomas and paragangliomas (PC/PGLs) are rare with limited data as to what the optimal management approach is. The aim of this study was to determine the role of genetic testing and imaging to detect extra-adrenal and/or metastatic tumors in pediatric PC/PGLs. Methods A retrospective study of 55 patients diagnosed at ≤ 21 years of age with PC/PGLs was performed with analysis of data on genetic testing and multimodal imaging. Results Eighty percent of patients (n=44/55) had a germline mutation. The majority were found to have either VHL (38%) or SDHB (25.4%) mutation. PC was present in 67% (n=37/55) of patients and was bilateral in 51.3% (n=19/37). The majority of patients with bilateral PC had VHL (79%). Abdominal PGL was present in 21.8% (n=12/55), head and neck PGL in 11% (n=6/55) and thoracic PGL in 3.6% (n=2/55) of patients. For PGL, SDHx accounted for 72% (n=13/18) of mutations. The rate of malignancy was 16.4% (n=9/55), 55.5% had SDHB mutations. In two-thirds of patients, functional imaging identified either extra-adrenal PGL and/or metastatic disease. Conclusions The majority of pediatric patients with PC/PGL have germline mutations. Therefore, all pediatric patients with PC/PGLs require genetic testing and imaging to detect extra-adrenal PGL and metastatic disease to guide treatment and follow up.

Context. The reliable localization of insulinoma is critical for the successful surgical treatment.Objective. This study compared the accuracy of 68 Gallium (Ga)-DOTATATE PET/CT to anatomic imaging modalities, selective arterial secretagogue injection (SASI), and intraoperative ultrasound (IOUS) and palpation for localizing insulinoma in patients who were biochemically cured. Design, Setting, and Patients. We conducted a retrospective analysis of 31 patients who had an insulinoma confirmed on histology and were biochemically cured. The results of CT, MRI, transabdominal US, IOUS, 68 Ga-DOTATATE PET/CT, SASI, and operative findings were analyzed. Intervention, Main Outcome Measures, Results: The insulinomas were correctly localized in 17 out of 31 (55%) of patients by CT, in 17 out of 28 (61%) by MRI, in 6 out of 28 (21%) by US, and in 9 out of 10 (90%) by 68 Ga-DOTATATE. IOUS was performed in 31 patients, and 29 of them had an insulinoma successfully localized (93.5%). Thirty patients underwent SASI, and the insulinoma was regionalized in 28 out of 30 patients (93%). In 19 out of 23 patients (83%), manual palpation identified insulinoma. In patients who had all four noninvasive imaging studies, CT was concordant with 68 Ga-DOTATATE in 6 out of 9 patients (67%); MRI in 8 out of 9 (78%); US in 0 out of 9; and in 1 out of 9 patients (11%) the lesion was only seen by 68 Ga-DOTATATE. Conclusions:68 Ga-DOTATATE PET/CT identifies most insulinomas and may be considered as an adjunct imaging study when all imaging studies are negative and when a minimally invasive surgical approach is planned.PRECIS: We studied 68Ga-DOTATATE PET/CT imaging in patients with insulinoma and found it identifies most tumors and should be considered as an adjunct imaging study.

Recurrent hypoglycemia is a common problem among infants and children that is associated with several metabolic disorders and insulin-dependent diabetes mellitus. Although studies have reported a relationship between a history of juvenile hypoglycemia and psychological health problems, the direct effects of recurrent moderate hypoglycemia have not been fully determined. Thus, in this study, we used an animal model to examine the effects of recurrent hypoglycemia during the juvenile period on affective, social, and motor function (assessed under euglycemic conditions) across development. To model recurrent hypoglycemia, rats were administered 5 U/kg of insulin or saline twice per day from postnatal day (P)10 to P19. Body weight gain was retarded in insulin-treated rats during the treatment period, but recovered by the end of treatment. However, insulin-treated rats displayed increases in affective reactivity that emerged early during treatment and persisted after treatment into early adulthood. Specifically, insulin-treated pups showed increased maternal separation-induced vocalizations as infants, and an exaggerated acoustic startle reflex as juveniles and young adults. Moreover, young adult rats with a history of recurrent juvenile hypoglycemia exhibited increased fear-potentiated startle and increases in behavioral and hormonal responses to restraint stress. Some of these effects were sex-dependent. The changes in affective behavior in insulin-exposed pups were accompanied by decreases in adolescent social play behavior. These results provide evidence that recurrent, transient hypoglycemia during juvenile development can lead to increases in fear-related behavior and stress reactivity. Importantly, these phenotypes are not reversed with normalization of blood glucose and may persist into adulthood.