Evaluation of Risk Factors and Approach to Screening for Asymptomatic Neonatal Hypoglycemia

<b><i>Introduction:</i></b> Protocols to identify asymptomatic neonatal hypoglycemia (NH) rely on the presence of established risk factors (late preterm gestation, large or small for gestational age, and infant of a diabetic mother) for inclusion. We analyzed the performance of these risk factors in identifying hypoglycemia in modern practice, and additionally evaluated the optimal duration of screening blood glucose measurements. <b><i>Methods:</i></b> We analyzed a retrospective cohort of 830 infants with 1 or more known risk factor(s) for NH admitted to the mother-baby unit of a single tertiary-care center from May 2017 to April 2018. Manual chart review was performed for data extraction and confirmation of risk factor(s). Infants were excluded if glucose measurements were obtained for any reason other than screening for asymptomatic NH. <b><i>Results:</i></b> Of the 830 included infants, 31 (3.7%) ultimately received intravenous dextrose (IVD). Most screened infants (<i>n</i> = 510, 61.4%) did not develop hypoglycemia. None of the established risk factors showed strong association with hypoglycemia. Cesarean delivery was associated with hypoglycemia, although not strongly. All infants who received IVD for feeding-refractory hypoglycemia were identified by the first 2 measurements with nearly all (30/31, 97%) identified at the initial measurement. <b><i>Conclusions:</i></b> Currently accepted risk factors are limited in their ability to identify infants who subsequently develop hypoglycemia, and as a result, most screened infants do not develop hypoglycemia. The majority of infants in our cohort who did develop hypoglycemia achieved normoglycemia with feeding-based interventions and did not require IVD. Those that received IVD were more likely to develop hypoglycemia early and to a more severe degree. Together, our data suggest further refinement of protocol duration and risk factors utilized for screening as potential areas of screening protocol optimization.

Severe recurrent hypoglycaemia in a patient with aggressive melanoma

. We present a case of hypoglycemia in a young patient without diabetes mellitus who presented initially with enlarging neck mass and weight loss, and was found to have aggressive melanoma with metastasis to multiple organs and diffuse lymphadenopathy. He had presented to the emergency room two times with neuroglycopenic symptoms that required admission and intravenous dextrose continuously. Evaluation of hypoglycemia included C-peptide, insulin levels, insulin-like growth factor (IGF) -I and -II, and ß- hydroxybutyrate. Insulin levels were suppressed appropriately during hypoglycemia, however, IGF-II:IGF-I ratio was high, suggesting non-islet tumour induced hypoglycemia. The presence of IGF-II produced by large tumors results in a low hepatic glucose output and increased uptake by skeletal muscle, resulting in hypoglycemia especially in a patient with extremely low appetite such as our patient. Treating the culprit malignancy leads to resolution of hypoglycemia, but corticosteroids have been used to suppress IGF-II levels and alleviate symptoms.

Out-of-Hospital Management of Diabetic Emergencies in Germany: Structural and Process Quality

Aims To collect and analyse representative data of structural and process quality in the management of diabetic emergencies in Germany in 2020. Methods A standardised questionnaire comprising detailed items concerning clinically relevant parameters on the structural and process quality of out-of-hospital management of diabetic emergencies was sent nationwide to medical directors of emergency medical service districts (EMSDs). Results were compared with those from a similar study conducted in 2001. Results The return rate of the questionnaires represented 126 EMSDs, serving a total population of > 40.1 million. Only 4% of ambulances carried glucagon (6% in 2001). In 2020, blood glucose determination increased significantly to 71% of all emergency interventions and to 29% of suspected cardiac emergencies (24% and 15%, respectively, in 2001). In 100% of EMSDs severe hypoglycaemia (SH) was treated by paramedics by administering intravenous dextrose before the arrival of a doctor compared to 63% in 2001. The potential value of nasal glucagon was acknowledged by 43% of responders. In selected patients, treatment of SH was conducted without hospital admission in 78% of EMDs (60% in 2001). Fifty-three percent of medical directors acknowledged the need for further training in diabetic emergencies (47% in 2001). Cooperation for medical education between emergency teams and a diabetes centre was reported by 14% (41% in 2001). Conclusion Structural and process quality of the management of diabetic emergencies in Germany has improved considerably since 2001. Persisting deficiencies could be improved by providing better medical equipment in ambulances and ongoing education to the entire emergency teams.

Continuous Glucose Monitoring in the Management of Hypoglycemia in TANGO2

Introduction: The TANGO2 gene encodes a transport and Golgi organization protein of unclear function; mutations should be considered in patients presenting with acute metabolic crisis, hypoglycemic episodes, cardiac arrhythmias, and other endocrinopathies. We report the novel use of a continuous glucose monitor (CGM) to help predict and prevent significant hypoglycemic episodes in a patient with TANGO2 mutation. Clinical Case: A 14-month old previously healthy, developmentally normal female who presented with unresponsive hypoglycemia (glucose 26 mg/dL) was demonstrated by Next Generation Sequencing to have a pathogenic 31.8 kb deletion of exon 3 to 9 in the TANGO-2 gene and a suspected pathogenic hemizygous c.569_592dup, p.Ile190_Leu197dup in TANGO-2. Her hospital course was notable for MRI showing hypoxic ischemic encephalopathy and both physical and electrical cardiac dysfunction. Continuous intravenous dextrose corrected the hypoglycemia, and transient hyperglycemia followed after several days of a glucose infusion rate between 3.2 to 5.8 mg/kg/min. After transitioning to ad lib oral feeds without restrictions, she was discharged. A second admission for acute unresponsive hypoglycemia and metabolic acidosis (glucose 30 mg/dL) occurred at 17 months of age with no clear inciting cause. Continuous IV dextrose at 9.9 mg/kg/min corrected the hypoglycemia and again resulted in transient hyperglycemia up to 271 mg/dl. Levothyroxine was also started for a TSH of 27 mIU/mL and a T4 of 4.6 ug/dL. Immediately after discharge, a DexCom G6 CGM was placed. Data over 2 weeks shows an average glucose of 104 ng/dL with 99% of the BS in target range. Parents report that CGM predictive low alerts have allowed intervention to abort fasting-related metabolic crises. Conclusion: In TANGO-2 deficiency, the liver may not adequately store and/or release glycogen in response to glucagon due to abnormal endoplasmic reticulum, Golgi apparatus, and mitochondrial functioning in states of stress or illness. Recent reports are conflicting with some showing reduced mitochondrial respiration in TANGO-2 patients in steady state with others finding normal values, opening the possibility that a combination of factors in the setting of stress may precipitate a metabolic crisis. Our patient quickly returns to near-normal physiological functioning; consequently, we suggest that use of a CGM can help prevent fasting related metabolic crisis in TANGO2 patients and can help guide feeding schedule and food choices to limit hyper- and hypoglycemia. In addition, CGM data can help further investigate if any beta cell dysregulation exists in non-acute states. References: Bérat CM, ... & de Lonlay P. (2020). Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises.... J Inherit Metab Dis. 2020 Sep 14. doi: 10.1002/jimd.12314.

Trimethoprim–sulfamethoxazole-induced refractory hypoglycaemia successfully treated with octreotide

Trimethoprim–sulfamethoxazole (TMP–SMX) is a commonly prescribed antimicrobial agent for a wide variety of infections. It is generally well tolerated in a majority of patients; however, serious adverse effects have been described with its usage. Hypoglycaemia is an exceedingly rare but potentially life-threatening side effect of this antimicrobial agent due to its sulfonylurea-like effect. We describe a case of symptomatic, refractory hypoglycaemia secondary to TMP–SMX in a patient being treated for Stenotrophomonas maltophilia bacteraemia, which required treatment with 10 hours of intravenous dextrose (including several 50% dextrose boluses), as well as intramuscular glucagon and octreotide. We reviewed previous case reports described in the literature of TMP–SMX-induced hypoglycaemia, in which renal insufficiency was noted to be a common predisposing risk factor in an overwhelming majority of cases. In refractory cases of TMP–SMX-induced hypoglycaemia, intravenous octeotride may be considered for treatment.

Hypoglycemia and seizures associated with canine primary hepatic neuroendocrine carcinoma

A 10-y-old intact male Labrador Retriever dog had a history of ataxia, inability to stand, and grand mal seizures. Complete blood count and serum biochemistry profiles revealed profound hypoglycemia, mildly increased alanine aminotransferase (ALT) activity, mild hypernatremia, and lymphopenia. The seizures could not be controlled with intravenous dextrose, diazepam, or propofol. The dog was euthanized given poor quality of life, and an autopsy was performed. Primary autopsy findings included firm hepatic masses that ranged from dark-red to tan, with the largest ~1.5 cm diameter, and pulmonary edema. Histologic examination of the hepatic masses revealed redundant, several-cell-thick cords, and packeted or acinar arrangements of polygonal cells, supported on a fibrovascular stroma. The neoplastic cells were immunopositive for insulin, synaptophysin, and neuron-specific enolase immunohistochemistry; granules in the tumor cells had an affinity for Grimelius silver stain. The histologic features, as well as the immunohistochemical staining profile, identified the neoplasm as a primary multifocal hepatic neuroendocrine carcinoma. Neuroendocrine carcinomas are rare in dogs and usually occur in the gastrointestinal or respiratory tract.

Fluid and Glucose

The fluid and glucose chapter focuses primarily on unwell newborns who need early blood glucose monitoring for hypoglycemia and immediate stabilization with intravenous dextrose solution. But infants can be at risk for low blood glucose for many reasons, and they too need specific attention and care, even when they are not symptomatic. Oral doses of dextrose gel may help to raise blood glucose levels, which also depend on whether an infant cannot feed or should not be fed (for any reason) and response to supplementation or managed oral feeding. Guidance includes glucose thresholds to aim for, determined by postnatal age, and testing intervals to expedite the normalization of blood glucose values. How to assess, measure, and anticipate fluid requirements in at-risk infants is explained in detail, and risks for hypoglycaemia, dehydration, and overhydration are considered. Two case scenarios examine different hypoglycaemia risks.

Neurology

The neurology chapter examines mild, transient, and more serious, underlying neurological conditions that present in the newborn period. Abnormalities of tone, activity, alertness, and movements (i.e., seizures) can occur in many neonatal conditions, some of which require immediate intervention. Assessments include testing infant tone and reflexes, the Encephalopathy Assessment Table, distinguishing jitteriness from seizure activity, and identifying seizure characteristics. Early identification of infants with hypoxic ischemic encephalopathy—a primary cause of neonatal encephalopathy—is essential and should prompt either thermoregulatory management (strict normothermia) or therapeutic hypothermia, providing specific criteria are met. Symptomatic hypoglycemia can have long-term neurodevelopmental consequences and must be treated emergently with intravenous dextrose solution. Anticonvulsant therapy should be initiated for seizures, even when the underlying cause is not yet determined. Diagnostic testing and differential diagnoses, such as neonatal abstinence syndrome or neonatal opiate withdrawal are considered. Three case scenarios follow care pathways for two unwell infants.