Approach to hypoglycemia (pediatrics): Clinical sciences

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Introduction0:00–0:56

Hypoglycemia refers to a plasma glucose concentration that’s less than the lower limit of normal for age. Because the brain primarily relies on glucose as an energy source, prolonged hypoglycemia can cause serious adverse effects, such as seizures and permanent brain injury.
Infants less than 48 hours old frequently have transient physiologic hypoglycemia, while persistent hypoglycemia beyond 48 hours of life can be caused by medications or substances, as well as conditions unique to infancy and childhood, including inborn errors of carbohydrate metabolism, hypopituitarism, hyperinsulinism, fatty acid oxidation defects, disorders of gluconeogenesis, and ketotic hypoglycemic disorders.

Unstable Patient0:56–1:44

Now, if a pediatric patient presents with hypoglycemia, you should first perform an ABCDE assessment to determine if your patient is unstable or stable.
If unstable, stabilize the airway, breathing, and circulation. Next, obtain a fingerstick or heel stick glucose level, and obtain IV access to give IV dextrose.
In addition, begin continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, provide supplemental oxygen.
Here’s a clinical pearl! Be sure to consider sepsis in a newborn infant with hypoglycemia, especially if they are unstable or have temperature instability.

Stable Patient1:44–3:27

Now, let’s go back to the ABCDE assessment and discuss stable patients. In this case, first, obtain a focused history and physical examination, as well as bedside glucose followed by a critical lab sample to confirm the plasma glucose level.
Clinical manifestations of hypoglycemia differ based on age, with newborns and infants displaying symptoms like poor feeding, lethargy, or irritability; while an older child may report weakness, drowsiness, confusion, or hunger.
Meanwhile, the physical exam in a newborn or infant might reveal pallor, jitteriness, and occasionally, seizures; while an older child may display confusion, diaphoresis, or weakness.
In both cases, the bedside glucose will be less than 50 to 60 milligrams per deciliter. Finally, if the plasma glucose is less than 50 milligrams per deciliter in newborns under 48 hours of age, and less than 60 milligrams per deciliter in infants or children over 48 hours of age, you can diagnose hypoglycemia.
Here’s a clinical pearl! Hypoglycemic disorders are much less common in older children, so always assess verbal patients for the Whipple triad before beginning further evaluation.
Criteria include a documented low plasma glucose concentration, signs or symptoms consistent with hypoglycemia, and relief of those signs or symptoms after ingesting glucose.

Assess age3:27–4:16

Once you diagnose hypoglycemia, your first step is to assess your patient’s age. For infants less than 48 hours old, consider transient hypoglycemia, which is common in the first 2 days of life due to transient physiologic hyperinsulinism.
These infants are often small or large for gestational age, preterm, or infants of a diabetic mother. In this case, give your patient glucose, either by feeding the infant, or by giving IV dextrose if they are unable to feed.
Next, reassess the blood glucose level after 48 hours of age. If the hypoglycemia has resolved by that time, diagnose transient hypoglycemia of the newborn.

Less than 48 hours4:16–4:30

On the other hand, hypoglycemia that persists after 48 hours of age is likely to be pathologic, so in this case you should consider a persistent hypoglycemic disorder.
Before we proceed with an evaluation, let’s go back and discuss hypoglycemic patients who present after 48 hours of age.

Medication/substance effect4:30–5:13

In these patients, consider the possibility of medication or other substance effects, especially if your patient has diabetes.
Some common medications associated with hypoglycemia include insulin, sulfonylureas, or beta-blockers. Additionally, alcohol ingestion frequently causes hypoglycemia in children, since it’s often found in mouthwash and can be accidentally ingested.
If there’s a known or suspected ingestion of any, your patient is likely dealing with medication- or substance-induced hypoglycemia!
On the flip side, if you rule out medications and substances associated with hypoglycemia, you should consider a persistent hypoglycemic disorder.

Persistent hypoglycemic disorder5:13–5:35

In this case, begin your workup by assessing the timing of hypoglycemia in relation to a feeding, since this can provide clues to the underlying cause.

Postprandial hypoglycemia5:35–6:19

If your patient’s hypoglycemia is only postprandial, consider an inborn error of carbohydrate metabolism. Your next step is to order labs, including urine non-glucose reducing substances and molecular genetic testing, and don’t forget to review your patient’s newborn screen results, if available.
Now, if urine non-glucose reducing substances are positive, and the newborn screen detects no GALT activity, you can diagnose galactosemia.
However, if urine non-glucose reducing substances are positive, and genetic testing confirms a mutation of ALDOB, diagnose hereditary fructose intolerance.
Now, let’s switch gears and consider cases in which hypoglycemia occurs randomly or during a period of fasting. In this case, your first step is to order labs, including a comprehensive metabolic panel, or CMP; serum ketones, which are typically measured as beta-hydroxybutyrate; as well as lactate and free fatty acids.

Fasting/random hypoglycemia6:19–6:49

During your workup, be sure to collect blood samples during an episode of hypoglycemia! Next, assess whether or not there’s acidosis.

Assess for Acidosis - No Acidemia6:49–7:17

If the serum bicarbonate is 18 milliequivalents per liter or greater, there’s no acidosis, so look for features suggestive of hypopituitarism.
These include midline defects, such as cleft lip and palate, cholestatic jaundice, and microphallus if your patient is biologically male.
If any of these features are present, consider hypopituitarism, and check serum IGF-1 and cortisol levels. If they’re both low, order provocative tests of both growth hormone and ACTH secretion, as well as an MRI of the brain.

Hypopituitarism7:17–7:51

Inadequate hormone response to stimulation as well as MRI findings demonstrating a pituitary defect, such as an absent septum pellucidum, confirms congenital hypopituitarism.
On the flip side, let’s take a look at when the features of hypopituitarism are absent. When the features are absent, it’s likely your patient has an insulin-mediated disorder or a fatty acid oxidation disorder.

No hypopituitarism7:51–8:14

You can assess the serum beta-hydroxybutyrate and free fatty acid levels to distinguish between these. Now, if the beta-hydroxybutyrate and free fatty acids are both low, consider an insulin-mediated disorder, and obtain serum insulin and C-peptide levels.

Hyperinsulinism8:14–9:47

Detectable levels of insulin and C-peptide are suggestive of hyperinsulinism. But, to confirm your suspicions, assess the blood glucose response to a dose of intravenous or intramuscular glucagon.
A blood glucose increase of more than 30 milligrams per deciliter confirms the diagnosis of congenital hyperinsulinism. This heterogeneous disorder can be caused by various genetic mutations that result in inappropriate insulin secretion.
Hyperinsulinism is also a feature of some genetic syndromes, including Beckwith-Wiedemann syndrome, which presents with somatic gigantism, macroglossia, omphalocele, and hemihypertrophy.
Finally, infants with perinatal stress, prematurity, or those born small for gestational age are at risk for developing prolonged hyperinsulinism, with hypoglycemia persisting beyond 48 hours of age.
Here’s a clinical pearl! High plasma insulin levels in the setting of undetectable C-peptide suggest exogenous insulin administration.
If your patient doesn’t have diabetes, these findings should lead you to suspect surreptitious insulin administration! Now, let’s go back and take a look at patients with low serum beta-hydroxybutyrate and elevated free fatty acids.

Fatty acid oxidation disorder9:47–10:26

These findings should lead you to consider a fatty acid oxidation disorder, so as a next step, order a plasma acylcarnitine profile.
An elevation in medium, long, or very long chains of fatty acids suggests a fatty acid oxidation defect, so order enzyme or genetic testing for confirmation.
If testing identifies an enzyme or genetic defect, diagnose a fatty acid oxidation disorder. Alright, now that we’ve discussed hypoglycemia that occurs in the absence of acidosis, let’s go back and look at hypoglycemic patients who are acidotic.

Assess for Acidosis - Acidemia10:26–10:53

This means that the serum bicarbonate levels are less than 18 milliequivalents per liter. These cases are typically caused by disorders of gluconeogenesis or ketotic hypoglycemic disorders.
In this case, first, assess the source of acidosis by reviewing the serum lactate and beta-hydroxybutyrate levels. Moreover, elevated lactate levels and low beta-hydroxybutyrate levels are suggestive of gluconeogenesis disorders.

Disorder of gluconeogenesis10:53–11:43

As a next step, obtain molecular genetic testing, and if it reveals a mutation in the FBP1 gene, diagnose fructose-1,6-bisphosphatase deficiency.
On the other hand, if genetic testing reveals a mutation in the G6PC gene, you can diagnose glycogen storage disease type I, or GSD I.
These patients typically present with massive hepatomegaly and a doll-like face. Now, let’s switch gears and consider cases in which a hypoglycemic patient has acidosis with elevated serum beta-hydroxybutyrate levels.

Ketotic hypoglycemic disorder11:43–12:05

These findings should make you consider ketotic hypoglycemic disorders, so your next step is to assess your patient for hepatomegaly.
If hepatomegaly is present, consider glycogen storage disease types 0, III, VI, and IX, and order molecular genetic testing.

GSD 0/III/VI/IX12:05–12:21

If you identify a mutation, your patient has one of these glycogen storage diseases. If there’s no hepatomegaly, consider the possibility of adrenal insufficiency, and obtain a serum cortisol level.

Primary adrenal insufficiency12:21–13:05

First, let’s focus on primary adrenal insufficiency! These individuals may present with skin and mucosal hyperpigmentation.
Lab results typically reveal low serum cortisol levels, as well as low aldosterone, and they may also demonstrate low serum sodium and elevated serum potassium levels.
Next, order an adrenocorticotropic hormone stimulation test, and if there’s little or no increase in serum cortisol, your patient has primary adrenal insufficiency.

Idiopathic ketotic hypoglycemia13:05–13:38

On the other hand, if the serum cortisol level is normal, diagnose idiopathic ketotic hypoglycemia. This is the most frequent cause of hypoglycemia in childhood and is usually triggered by an extended fasting period, often during an acute illness.
Because idiopathic ketotic hypoglycemia is a diagnosis of exclusion and no specific tests can confirm it, make sure to rule out other causes of hypoglycemia before making this diagnosis!
Alright, as a quick recap… When a pediatric patient presents with hypoglycemia, first assess their age. Newborns whose hypoglycemia resolves by 48 hours of age have transient hypoglycemia.

Review13:38–14:51

For patients over 48 hours of age with persistent hypoglycemia and no known medication or substance exposure, consider a persistent hypoglycemic disorder.
Postprandial hypoglycemia suggests galactosemia or hereditary fructose intolerance. If the hypoglycemia is random or fasting, assess whether or not there’s acidosis.
If there’s no acidosis, think of congenital hypopituitarism, congenital hyperinsulinism, and fatty acid oxidation disorder.
On the flip side, if there’s acidosis, think of fructose-1,6-bisphosphatase deficiency, glycogen storage diseases, as well as primary adrenal insufficiency.
Finally, if you rule out all previous conditions, the diagnosis is idiopathic ketotic hypoglycemia!
Approach to hypoglycemia (pediatrics): Video | Osmosis