Clinical Pearls & Morning Reports
Published September 28, 2022
What are some of the causes of severe, prolonged hypoglycemia in a newborn? Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: Congenital teratomas occur most often in what anatomic region?
A: Teratomas are the most common type of perinatal tumor, comprising approximately 37 to 52% of congenital neoplasms. Teratomas are more common in female patients than in male patients. Congenital teratomas are most likely to occur in the sacrococcygeal area. Sacrococcygeal teratomas are a type of extragonadal germ-cell tumor, and they typically contain immature neuroepithelium. In a patient with a sacrococcygeal teratoma, hyperinsulinism can be caused by a focus of inappropriate insulin secretion within the mass.
Q: What are some of the reasons that prolonged hypoglycemic may occur in a newborn?
A: There are maternal, fetal, and neonatal conditions that can confer a predisposition for a delayed or exaggerated glycemic transition in an infant and potentially lead to neonatal hypoglycemia. These conditions are associated with three mechanisms: decreased insulin sensitivity, decreased stores of glycogen, and increased insulin secretion. Infants who are born preterm or are small for gestational age may be affected by any or all of these mechanisms. Infants who are large for gestational age are thought to be affected by increased insulin secretion in utero that resulted in fetal overgrowth, regardless of whether the mother had received a diagnosis of diabetes. When a mother has diabetes, fetal hyperinsulinism develops in response to maternal hyperglycemia.
A: In the absence of typical risk factors, other causes of severe, prolonged hypoglycemia should be considered. These include foci of ectopic or dysregulated insulin production (congenital hyperinsulinism or another focus of ectopic insulin production), metabolic diseases (fatty-acid oxidation defects, organic acidemias, urea-cycle defects, or glycogen-storage disease), genetic syndromes (the Prader–Willi syndrome, the Beckwith–Wiedemann syndrome, the Kabuki syndrome, the Sotos syndrome, or the Turner syndrome), and endocrinopathies (hypopituitarism, growth-hormone deficiency, or congenital adrenal hyperplasia).
A: The Sotos syndrome is a rare disorder that is associated with hyperinsulinism and sacrococcygeal teratomas. Newborns with the Sotos syndrome can present with few physical manifestations. The Sotos syndrome is a genetic condition with cardinal features of overgrowth, developmental delays, and a characteristic facial appearance. Overgrowth may occur prenatally or postnatally and can manifest as macrocephaly and tall stature. Among patients with the Sotos syndrome, neurodevelopmental findings vary but can include developmental delays, intellectual disability, learning disability, or autism spectrum disorder. Facial features include a broad forehead, posteriorly rotated ears, a flat nasal bridge, anteverted nares, and a pointed chin. Sacrococcygeal teratoma has been reported as a rare presenting feature of the Sotos syndrome. Other tumors can also occur with this syndrome, but the overall risk of cancer is low. Infants with the Sotos syndrome are recognized to be at risk for neonatal hypoglycemia due to transient hyperinsulinism (separate from the risk of hyperinsulinism related to ectopic insulin production by a sacrococcygeal teratoma, if present). The Sotos syndrome is identified by the detection of pathogenic variants in the gene NSD1; more than 380 variants in this gene have been linked to this disease.