|Year : 2016 | Volume
| Issue : 2 | Page : 122-124
Hyperinsulinemic hypoglycemia and thrombocytopenia in a neonate: Treatment and review of literature
Liana Senaldi, Resmy Palliyil Gopi, Bina Shah
Department of Pediatrics, Division of Pediatric Endocrinology, New York University School of Medicine, New York, NY, USA
|Date of Web Publication||8-Apr-2016|
Department of Pediatrics, Divisions of Pediatric Endocrinology, New York University School of Medicine, 550 First Avenue, New York, NY 10016
Source of Support: None, Conflict of Interest: None
Transient hyperinsulinism and thrombocytopenia can occur in neonates following exposure to perinatal stress and birth asphyxia. However, little is known about whether there is a direct association between neonatal hyperinsulinism and thrombocytopenia. We report a case of transient hyperinsulinism and thrombocytopenia, both of which improved after administration of diazoxide in a full-term neonate born by emergency cesarean section and required resuscitation. The newborn had severe hypoglycemia at 8 h of life and continued to have episodes of hypoglycemia while on a continuous glucose infusion rate. The glucagon stimulation test was positive confirming hyperinsulinism and the patient was started on diazoxide. Concomitantly, the neonate also had severe thrombocytopenia and required four platelet transfusions in the first 8 days. Within 24 h after starting diazoxide, both blood glucose and platelet counts improved. We speculate a possible association of hyperinsulinism with thrombocytopenia.
Keywords: Hyperinsulinism, hypoglycemia, thrombocytopenia
|How to cite this article:|
Senaldi L, Gopi RP, Shah B. Hyperinsulinemic hypoglycemia and thrombocytopenia in a neonate: Treatment and review of literature. J Clin Neonatol 2016;5:122-4
|How to cite this URL:|
Senaldi L, Gopi RP, Shah B. Hyperinsulinemic hypoglycemia and thrombocytopenia in a neonate: Treatment and review of literature. J Clin Neonatol [serial online] 2016 [cited 2021 Jun 12];5:122-4. Available from: https://www.jcnonweb.com/text.asp?2016/5/2/122/179924
| Introduction|| |
Hypoglycemia in infants following perinatal stress and birth asphyxia is common. Reports have suggested that transient hyperinsulinism contributes to hypoglycemia in infants with perinatal stress. , It is also known that in small-for-gestational age infants, hypoglycemia results from depletion of glycogen stores secondary to stress-induced catecholamine release. ,
Early onset thrombocytopenia, diagnosed at <72 h of life, is one of the most common hematological problems encountered in the neonatal period. Thrombocytopenia can result from impaired production, consumption, and/or sequestration. 
The aim of this case report is to describe the clinical course of perinatal stress-associated hyperinsulinemia and thrombocytopenia, and to suggest a possible association between these two entities.
| Case Report|| |
The neonate is a baby boy, second of twin, born to a 36-year-old mother by emergency cesarean section for fetal bradycardia of the second twin. There was no history of maternal gestational diabetes or hypertension, and all prenatal labs were normal. The baby was born full term, depressed at birth, and required positive pressure ventilation, which improved APGAR scores from 4 at 1 min to 9 at 5 min. The baby had a birth weight of 2505 g and physical examination was unremarkable.
At 8 h of life, the baby had hypotonia and nasal flaring. The blood glucose (BG) was undetectable, and he was treated with IV dextrose. As the BG remained low, the baby was placed on intravenous fluids (IVF) D10 at a glucose infusion rate (GIR) of 6 mg/kg/min, which was later increased to a GIR of 8.6 mg/kg/min due to persistent hypoglycemia. A sepsis evaluation was performed and the infant was started on intravenous antibiotics.
On day of life (DOL) 3, the patient had multiple hypoglycemic episodes with BG <30 mg/dl, requiring multiple dextrose boluses and an increase in the GIR to 19.8 mg/kg/min. In the next few days as the BG remained above 50 mg/dl on IVF and feeds, the IV rate was gradually weaned to a GIR of 7 mg/kg/min. On DOL 8, baby had a BG of 29 mg/dl, at which time critical labs were drawn and a glucagon stimulation test was performed. The glucagon test showed a positive result with an increase in BG more than 30 mg/dl in 30 min and an insulin level of 5 uIU/mL, cortisol level of 16.5 mcg/dl, a growth hormone level of 22 ng/mL, and a normal acylcarnitine profile.
As part of the evaluation for possible sepsis, the complete blood count revealed a platelet count of 24 × 10 9 /l and a mean platelet volume of 14.6 (normal 6-11 fl) on DOL 1 and the baby received a platelet transfusion. The baby's platelet count remained above 50 × 10 9 /l until DOL 4 when it decreased to 35 × 10 9 /l, requiring another platelet transfusion. In the next 2 days, platelet counts remained between 50 and 80 × 10 9 /l. The platelet counts continued to drop and the baby required platelet transfusions daily for 3 consecutive days until DOL 9. Parental testing for platelet antigens and maternal platelet antibodies was negative. Diepoxybutane clastogen assay for Fanconi anemia was negative and forearm x ray was normal with intact radius.
The positive glucagon test confirmed hyperinsulinism and the baby was started on diazoxide at 10 mg/kg/day on DOL 8. Within 24 h after starting diazoxide, glucose levels normalized and IVF was discontinued on DOL 11. Platelet counts increased to over 200 × 10 9 /l on DOL 9 and the patient did not require further transfusions after DOL 10. All cultures were negative and the baby completed a 10-day course of IV antibiotics. He was discharged home on DOL 15 on diazoxide at 10 mg/kg/day. As the BG remained above 100 mg/dl, diazoxide was slowly weaned and discontinued on DOL 19. Both BG and platelet counts remained normal after stopping diazoxide [Table 1].
|Table 1: Clinical course of neonate with hyperinsulinemia and thrombocytopenia |
Click here to view
| Discussion|| |
We present a case of perinatal stress-induced transient hyperinsulinism and early-onset thrombocytopenia, both of which improved after starting diazoxide treatment. Similar to our case, Mizumoto et al. reported three cases of transient hyperinsulinism with thrombocytopenia also complicated with cardiopulmonary problems and erythroblastosis, following exposure to perinatal stress and suggest that perinatal stress-associated hyperinsulinism can be regarded as a systemic syndrome.  Diazoxide acts as a potent potassium channel activator, which leads to the inhibition of insulin secretion and resolution of hypoglycemia.  Although diazoxide is known to worsen thrombocytopenia, we started our patient on the 8 th day of life with diazoxide, given the patient's refractory hypoglycemia. We started with a moderate dose with close monitoring of platelet counts. It was strikingly remarkable that within 24 h of starting diazoxide in our patient, both the BG and platelet counts improved.
As observed in our patient, early onset thrombocytopenia is common in neonates due to fetal hypoxia or placental insufficiency. Perinatal stress-associated thrombocytopenia is usually mild with low normal (150-200 × 10 9 /l) or borderline thrombocytopenia (100-150 × 10 9 /l). Platelet counts gradually reach a nadir at day 4 before recovering in 7-10 days and usually does not require any specific treatment.  Although the exact mechanism is unclear, studies suggest that acute hypoxia impairs platelet production by altering megakaryocyte structure and function, and also decreases platelet survival. , It was unusual that our patient had prolonged and severe thrombocytopenia, requiring four platelet transfusions in the first 8 days of life.
Many factors may have contributed to the improvement of thrombocytopenia in our patient, including natural resolution of the perinatal stress period and hypoglycemia, as well as resolution of hyperinsulinemia following the administration of diazoxide. The coexistence of hyperinsulinemia and thrombocytopenia and both acutely resolving with diazoxide treatment was very intriguing. While isoimmune thrombocytopenia has been shown to be associated with hyperinsulinemic hypoglycemia, we did not detect maternal antiplatelet antibodies excluding that diagnosis.  We speculate that there may have been a potential impact of hyperinsulinism on platelets, as in vitro studies revealed that platelets express the insulin and insulin-like growth factor-1 receptors.  There have been conflicting reports about the effects of insulin on platelet function. Some studies report that insulin can inhibit platelet activity, whereas other studies suggest that insulin can enhance platelet aggregation. 
| Conclusion|| |
We report a possible impact of hyperinsulinemia on thrombocytopenia in the neonatal period, albeit rare. Although the exact mechanism is unknown, further research is needed to evaluate the impact of insulin on platelet function.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Collins JE, Leonard JV. Hyperinsulinism in asphyxiated and small-for-dates infants with hypoglycaemia. Lancet 1984;2:311-3.
Sweet CB, Grayson S, Polak M. Management strategies for neonatal hypoglycemia. J Pediatr Pharmacol Ther 2013;18:199-208.
Lagercrantz H, Bistoletti P. Catecholamine release in the newborn infant at birth. Pediatr Res 1977;11:889-93.
Schultz K, Soltész G. Transient hyperinsulinism in asphyxiated newborn infants. Acta Paediatr Hung 1991;31:47-52.
Gunnink SF, Vlug R, Fijnvandraat K, van der Bom JG, Stanworth SJ, Lopriore E. Neonatal thrombocytopenia: Etiology, management and outcome. Expert Rev Hematol 2014;7:387-95.
Mizumoto H, Uchio H, Yamashita S, Hata D. Transient neonatal hyperinsulinism with adaptation disorders: A report of three cases. J Pediatr Endocrinol Metab 2015;28:337-40.
Boutaybi N, Steggerda SJ, Smits-Wintjens VE, van Zwet EW, Walther FJ, Lopriore E. Early-onset thrombocytopenia in near-term and term infants with perinatal asphyxia. Vox Sang 2014;106:361-7.
Adams JT, Donn SM. Association of isoimmune thrombocytopenia and neonatal hyperinsulinism/hypoglycemia. Am J Perinatol 1994;11:374-6.
Hunter RW, Hers I. Insulin/IGF-1 hybrid receptor expression on human platelets: Consequences for the effect of insulin on platelet function. J Thromb Haemost 2009;7:2123-30.
Hu H, Hjemdahl P, Li N. Effects of insulin on platelet and leukocyte activity in whole blood. Thromb Res 2002;107:209-15.