A case of neonatal persistent hyperinsulinemichypoglycemia

Mauro Iannelli, Alessandra Li Pomi, Fabio Sippelli, A. Spagnolo, I. Rulli, Fortunato Lombrado, Malgorzata Gabriela Wasniewska, Tommaso Aversa, Eloisa Gitto


Neonatal hypoglycemia (NH) is a common and important cause of morbidity in newborns. The most common cause of NH is congenital hyperinsulinism (CHI), a phenotypical and genotypical heterogeneous condition characterized by inappropriate insulin secretion. In our case a male, AGA, newborn from vaginal delivery at 37-week gestation, with no risk factors in maternal history, presented with asymptomatic hypoglycemia (30 mg/dL) at 30 minutes after birth. He was subsequently admitted to the NICU because of persistent hypoglycemia associated with symptoms development (peripheral tremors). Newborns can present with a wide variety of symptoms, including irritability, tremor, feeding impairment, coma, or be completely asymptomatic.

He was treated with continuous glucose infusions progressively increased to a rate of 12.7mg/kg/min. Because of persistent hypoglycemia (> 72h) and high i.v. glucose needs (>10 mg/kg/min) screening tests during fast-induced hypoglycemia were performed and isolated hyperinsulinism was detected. Oral medical therapy with diazoxide was started with benefit. Genetic testing was also performed to characterize CHI.

The diagnosis is usually based on clinical and biochemical findings. The mainstay of therapy is oral diazoxide administration. However, in cases refractory to medical therapy, 18F- DOPA-PET can be used to identify specific histological patterns which may need surgical intervention.  

Neonatal CHI-induced hypoglycemia should always be considered in the differential diagnosis of NH. Prompt diagnosis and genotypic characterization of CHI through clinical, biochemical, radiological, and genetic testing is fundamental for a proper therapeutic management of the condition and for prevention of neurological sequelae.


hypoglycemia; congenital; hyperinsulinism; diazoxide

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1. James, C., Kapoor, R. R., Ismail, D., & Hussain, K. (2009). The genetic basis of congenital hyperinsulinism. Journal of medical genetics, 46(5), 289–299.doi:10.1136/jmg.2008.064337

2. Dillon P. A. (2013). Congenital hyperinsulinism. Current opinion in pediatrics, 25(3), 357–361.doi:10.1097/MOP.0b013e3283600ebb

3. Hussain, K., & Aynsley-Green, A. (2003). Hyperinsulinism in infancy: understanding the pathophysiology. The international journal of biochemistry & cell biology, 35(9), 1312–1317.doi:10.1016/s1357-2725(03)00103-1

4. Otonkoski, T., Näntö-Salonen, K., Seppänen, M., Veijola, R., Huopio, H., Hussain, K., Tapanainen, P., Eskola, O., Parkkola, R., Ekström, K., Guiot, Y., Rahier, J., Laakso, M., Rintala, R., Nuutila, P., & Minn, H. (2006). Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA positron emission tomography. Diabetes, 55(1), 13–18.

5. Wang, W. Y., Sun, Y., Zhao, W. T., Wu, T., Wang, L., Yuan, T. M., & Yu, H. M. (2017). Congenital Hyperinsulinism in China: A Review of Chinese Literature Over the Past 15 Years. Journal of clinical research in pediatric endocrinology, 9(3), 194–201.doi:10.4274/jcrpe.3934

6. Senniappan, S., Shanti, B., James, C., & Hussain, K. (2012). Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. Journal of inherited metabolic disease, 35(4), 589–601.doi:10.1007/s10545-011-9441-2

7. Hussain, K., Blankenstein, O., De Lonlay, P., & Christesen, H. T. (2007). Hyperinsulinaemic hypoglycaemia: biochemical basis and the importance of maintaining normoglycaemia during management. Archives of disease in childhood, 92(7), 568–570.doi:10.1136/adc.2006.115543

8. Gutgold, A., Gross, D. J., Glaser, B., & Szalat, A. (2017). Diagnosis of ABCC8 Congenital Hyperinsulinism of Infancy in a 20-Year-Old Man Evaluated for Factitious Hypoglycemia. The Journal of clinical endocrinology and metabolism, 102(2), 345–349.doi:10.1210/jc.2016-3254

9. Ferrara, C., Patel, P., Becker, S., Stanley, C. A., & Kelly, A. (2016). Biomarkers of Insulin for the Diagnosis of Hyperinsulinemic Hypoglycemia in Infants and Children. The Journal of pediatrics, 168, 212–219.doi:10.1016/j.jpeds.2015.09.045

10. Kapoor, R. R., James, C., & Hussain, K. (2009). Advances in the diagnosis and management of hyperinsulinemic hypoglycemia. Nature clinical practice. Endocrinology & metabolism, 5(2), 101–112.doi:10.1038/ncpendmet1046

11. Lord, K., & De León, D. D. (2013). Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management. International journal of pediatric endocrinology, 2013(1), 3.doi:10.1186/1687-9856-2013-3

12. Garg, P. K., Lokitz, S. J., Truong, L., Putegnat, B., Reynolds, C., Rodriguez, L., Nazih, R., Nedrelow, J., Guardia, M., Uffman, J. K., Garg, S., & Thornton, P. S. (2017). Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism. PloS one, 12(11), e0186340.doi:10.1371/journal.pone.0186340

.Hasbaoui, B. E., Elyajouri, A., Abilkassem, R., & Agadr, A. (2020). Congenital hyperinsulinsim: case report and review of literature. The Pan African medical journal, 35, 53.doi:10.11604/pamj.2020.35.53.16604

DOI: https://doi.org/10.13129/1828-6550/APMB.110.1.2022.CCS4


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Copyright (c) 2022 Mauro Iannelli, A. Li Pomi, F. Sippelli, A. Spagnolo, I. Rulli, Fortunato Lombrado, Malgorzata Gabriela Wasniewska, Tommaso Aversa, Eloisa Gitto

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