• David Rayburn, MD, MPH

Sugar Problems

A Practical Approach to Pediatric Hypoglycemia

Nurse: Your patient in Room 4 is has a sugar of 35.

Me: Ok, cool, let’s get them some sugar!

If only that is where things ended. We know hypoglycemia is something that can be intervened on rapidly during initial assessment of the patient, but what happens after you have given dextrose? Why were they hypoglycemic in the first place? This is where the diagnostic challenge begins.

The differential diagnosis for hypoglycemia is expansive but having a method for working through this can really help save the day. For this post we will be focusing on the workup and broad differential diagnosis of hypoglycemia in toddlers and older children and will not be covering hypoglycemia in the neonate. We will also not be covering the different mechanisms on how to give the glucose beyond if they are awake give oral glucose and if they are not, give IV glucose.

Before we dive in, I think it is important for us to take a second and remember hypoglycemia is a serious metabolic derangement with potentially disastrous consequences if missed or treatment is delayed including seizures and brain damage leading to global developmental delays.

A quick recap of hypoglycemia symptoms: Usually manifest when blood glucose is less than 55-60 and include sweating, tremor, palpitations, tachycardia, and hunger. When blood glucose drops below 50 you can start to see lethargy, confusion, and even seizures.

When your patient presents with a blood glucose < 50, this is the threshold for aquiring more diagnostic data to help determine the cause and this is usually called the “critical sample” (1).

What is this critical sample you speak of? Glad you asked! There are a whole host of labs that are obtained, all of which serve a specific purpose of determining the cause of hypoglycemia.

Blood sample includes:

· plasma glucose* - Free fatty acids

· Beta-hydroxybutyrate - ammonia

· CMP - cortisol

· Insulin - growth hormone

· c-peptide - acyl-carnitine profile

· free and total carnitines

Urine sample:

· Ketones

· organic acids

*Plasma glucose levels should be used instead of whole blood glucose due to whole blood levels typically being 10-15% lower than plasma levels (2).

The critical sample can be obtained during the initial episode, if it does not delay glucose administration, or during a diagnostic fast to recreate hypoglycemia in a controlled environment with easy access to treatment (1).

Once the sample is obtained you are able to use the results to start to work through the differential. There are broad categories of diagnoses which are categorized by levels of lactate, ketones, and FFAs. The Pediatric Endocrine Society (insert link to study here) published guidelines in 2015, see table below.

Figure 1: Algorithm hypoglycemic disorders based on critical sample obtained during an episode of hypoglycemia.

First thing is to determine is the patient is acidotic or not.

No Acidosis

Next, determine if Free fatty acids (FFA) and Ketones are up or down. If they are both down this suggests an insulin-mediated hypoglycemic disorder. Consider hyperinsulinism, insulinoma, factitious hypoglycemia, or oral hypoglycemic ingestion. You can use insulin and c-peptide levels to help distinguish between some of these diagnoses. Insulin up and no c-peptide then there is likely exogenous insulin administration. If there are detectable insulin and c-peptide levels consider hyperinsulinism, sulfonylurea ingestion or insulinoma (1).

If the FFA are up and ketones are down, then the differential is usually a fatty acid oxidation defect such as MCADD of VLCADD (1). The plasma acyl-carnitine profile will help determine the specific disorder.


Next step is to look at ketones and lactate (acids). If the ketones are elevated, this suggests a ketotic hypoglycemic disease, and you should consider glycogen storage disease (GSD), growth hormone (GH) deficiency, cortisol deficiency, or idiopathic ketotic hypoglycemia.

If you find that lactate is elevated, this suggests a problem with gluconeogenesis (1). Consider pyruvate carboxylase deficiency, GSD I, or Fructose 1,6- bisphosphatase deficiency. You will likely see elevated liver enzymes, triglycerides, and uric acid.

To close things out, if we consider diagnoses by age group:

- First two years of life- GSD, GH, and cortisol deficiency

- Toddlers and young children- Ingestions, ketotic hypoglycemia, GSDs

- School-aged children and adolescents- Insulinoma, factitious hypoglycemia, other ingestions


· Treat the hypoglycemia first! Figure out what caused it after

· Obtain your critical sample (labs above) when blood glucose <50, this can be done during the initial episode or during a controlled fast

· Categories of disorders are insulin-mediated, fatty acid oxidation, ketotic hypoglycemia, and disorders of gluconeogenesis

· Determining acidosis or not will narrow your differential quickly then you can look at ketones, lactate, and FFA to help narrow further


1. DeLeon D, Lord K, Wolfsdorf J. Diagnostic approach to hypoglycemia in infants and children. UptoDate. https://www.uptodate.com/contents/diagnostic-approach-to-hypoglycemia-in-infants-and-children?search=hypoglycemia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1Accessed on February 16, 2020.

2. Gandhi K,. Approach to hypoglycemia in infants and children. Translational Pediatrics. 2017; 6(4):408-420.

3. Thornton P, Stanley C, DeLeon D, Harris D, Haymond M, Hussain K, Levitsky L, Murad M, Rozance P, Simmons R, Sperling M, Weinstein D, White N, Woldsdorf J. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. Journal of Pediatrics. 2015; 167(2): 238-245.

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