Approach To Hypoglycemia in Infants and Children

Approach to hypoglycemia in infants and children - UpToDate 24/04/22 12.
43
Official reprint from UpToDate®

www.uptodate.com © 2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Approach to hypoglycemia in infants and children

Authors: Diva D De Leon-Crutchlow, MD, MSCE, Katherine Lord, MD
Section Editor: Joseph I Wolfsdorf, MD, BCh
Deputy Editor: Alison G Hoppin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2022. | This topic last updated: Jul 08, 2021.
INTRODUCTION
Hypoglycemic disorders are rare, but their consequences, particularly for children, can be
severe and disabling. Hypoglycemia may result in seizures and brain damage, which lead
to developmental delays, physical and learning disabilities, and, in rare cases, death [1,2].
Given these severe consequences, the prompt diagnosis and appropriate management of
hypoglycemic disorders in children are crucial.
The differential of hypoglycemic disorders is broad, and it is essential to have a systematic

approach when evaluating a child with hypoglycemia. The vast majority of hypoglycemic
events in infants and children with hypoglycemic disorders occur during periods of
fasting. This allows for categorization of hypoglycemia disorders by their specific profiles
of metabolic fuels and hormones in the fasting state or during an episode of spontaneous
hypoglycemia [3]. Therefore, a diagnosis can be rapidly and accurately obtained by
assessing the child's metabolic and hormonal response to fasting ( algorithm 1).
Glucose homeostasis and the diagnostic approach to hypoglycemia in infants and children
will be discussed here. Other topics with related content include:
● (See "Causes of hypoglycemia in infants and children".)

● (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia".)
● (See "Management and outcome of neonatal hypoglycemia".)
● (See "Hypoglycemia in children and adolescents with type 1 diabetes mellitus".)
https://www.uptodate.com/contents/approach-to-hypoglycemia-in-infants-and-children/print Page 1 of 31
Approach to hypoglycemia in infants and children - UpToDate 24/04/22 12.43
● (See "Pathogenesis, clinical presentation, and diagnosis of congenital

hyperinsulinism".)
● (See "Treatment and outcomes of congenital hyperinsulinism".)
GLUCOSE HOMEOSTASIS IN NORMAL INFANTS AND CHILDREN
Glucose is the preferred fuel of the brain, which can only store trivial amounts of glucose
in the form of glycogen. To ensure an adequate supply of glucose to the brain, the body
must successfully adapt to fasting. Multiple systems regulate glucose homeostasis and
control the transition from the fed to fasting state. Abnormalities in these "fasting
regulatory systems" result in the disorders of hypoglycemia.
In response to fasting, key changes in the endocrine system occur: insulin is suppressed
and the serum concentrations of the counterregulatory hormones (glucagon, cortisol,
growth hormone, and epinephrine) rise. These hormonal changes activate the three
metabolic "fasting systems" (glycogenolysis, gluconeogenesis, lipolysis and ketogenesis),
which lead to increased hepatic glucose production, a gradual decrease in glucose
utilization, and an increase in availability of alternative fuels ( table 1):
● Initially, during fasting, the liver is the primary source of glucose, generated through
breakdown of glycogen and production of glucose from amino acids, glycerol, and
lactate via gluconeogenesis.
● With more prolonged fasting, the body switches to adipose tissue as the major
source of fuel [4]. Lipolysis and ketogenesis lead to an increase in free fatty acids
(FFAs) and the ketone bodies beta-hydroxybutyrate (BOHB) and acetoacetate.
● As glucose production declines and ketones levels increase, the brain gradually
switches to ketones as its main fuel [5].
Glucose homeostasis and the metabolic response to fasting do not differ significantly
between infants after the first two to three days of life, children, and adults. However,
glucose levels decline more rapidly and the transition to ketogenesis occurs earlier in
infants and young children compared with older children and adults, given infants'
relatively larger brain volume and higher glucose utilization rates. The transition to
ketogenesis occurs after fasting for 12 to 18 hours in neonates and infants, while in older
children and adults, this transition may take up to 24 to 48 hours of fasting [6].
CLINICAL FEATURES
Symptoms of hypoglycemia can be divided into neurogenic and neuroglycopenic

symptoms:
● Neurogenic (autonomic) symptoms are caused by the sympathetic nervous system's

response to hypoglycemia and appear when the plasma glucose is less than 55 to 60
mg/dL. Manifestations are sweating, tremor, palpitations, tachycardia, and hunger.
● Neuroglycopenic symptoms result from insufficient supply of glucose to the brain,

leading to brain dysfunction. They include lethargy, confusion, irritability, loss of
consciousness, and seizure. Neuroglycopenic symptoms typically occur when the
plasma glucose falls below 50 mg/dL.
Although neurogenic symptoms may serve as warnings before more severe hypoglycemia
occurs, repeated exposure to hypoglycemia can blunt or eliminate these symptoms and
the counterregulatory hormone response to hypoglycemia. This is known as
hypoglycemic-associated autonomic failure (HAAF) or "hypoglycemia unawareness" and
may result in individuals presenting with lower plasma glucose values and
neuroglycopenic symptoms [7]. Features of HAAF have been demonstrated to occur even
in infants [8]. (See "Hypoglycemia in children and adolescents with type 1 diabetes
mellitus", section on 'Symptoms and signs'.)
● Older children and adults – Hypoglycemia in these age groups typically

demonstrates the Whipple triad:
• Symptoms and signs consistent with hypoglycemia

• A documented low plasma glucose concentration
• Resolution of the symptoms with normalization of the glucose concentration
● Infants and toddlers – Symptoms in these age groups are frequently nonspecific
and include irritability, lethargy, poor feeding, cyanosis, and tremor or jitteriness.
Commonly, infants manifest no symptoms of hypoglycemia until they present with a
hypoglycemic seizure.
Many hypoglycemia disorders have specific clinical features that can provide important
clues to their diagnosis. (See "Causes of hypoglycemia in infants and children".)
INDICATIONS FOR EVALUATION
In 2015, the Pediatric Endocrine Society, through a committee composed of pediatric

endocrinologists and neonatologists, published recommendations for the evaluation and
management of hypoglycemia in neonates, infants, and children [9]. The
recommendations outline which neonates, infants, and children should be evaluated for a
hypoglycemic disorder according to their ability to communicate symptoms:
● For neonates, evaluate those who are suspected to be at high risk of having a
persistent hypoglycemia disorder ( table 2). The diagnostic evaluation should be
performed when the infant is at least 48 hours of age.
● For infants and younger children who are unable to reliably communicate symptoms,
evaluate those whose plasma glucose concentrations are <60 mg/dL (3.3 mmol/L), as
documented by a laboratory-quality assay (a point-of-care test is not sufficient).
● For children who are able to communicate their symptoms, evaluate those who
demonstrate Whipple triad (symptoms consistent with hypoglycemia, low plasma
glucose concentration, and resolution of symptoms with normalization of plasma
glucose). (See 'Clinical features' above.)
DIAGNOSIS OF HYPOGLYCEMIA
Hypoglycemia is defined as a plasma glucose concentration low enough to cause signs

and symptoms of brain dysfunction (neuroglycopenia). Because the response to
hypoglycemia occurs across a range of plasma glucose concentrations and signs of
hypoglycemia are not reliably identifiable, especially in young children, and vary among
individuals, hypoglycemia cannot be defined as a single plasma glucose concentration.
However, a threshold to obtain diagnostic data and a therapeutic threshold goal are
presented below:
● Normal plasma glucose – After the first week of life, the normal range for plasma
glucose is 70 to 100 mg/dL (3.9 to 5.6 mmol/L). Normal newborns experience a
period of "transitional" hypoglycemia during the first 48 to 72 hours of life. A study of

68 healthy full-term newborns found a mean plasma glucose concentration of 59±11
mg/dL during the first 48 hours of life. The plasma glucose concentration increased
to a mean of 82±12 mg/dL by 72 to 96 hours of life [10-12].
● Diagnostic threshold – The threshold for obtaining diagnostic data (often referred
to as the "critical sample") and for confirming a diagnosis of hypoglycemia is <50
mg/dL (2.8 mmol/L), as documented by a laboratory-quality assay. This threshold is
sufficiently low to avoid false-positive results but is unlikely to cause lasting
neurologic sequelae.
● Treatment goal – To provide a margin of safety, the treatment goal for children with
hypoglycemic disorders is to maintain a plasma glucose >70 mg/dL (3.9 mmol/L).
(See 'Treatment' below.)
IMMEDIATE MANAGEMENT
The immediate management of a child with hypoglycemia involves rapid normalization of

the plasma glucose concentration via oral carbohydrates and/or parenteral glucose (
table 3). If the child's mental status is appropriate and a blood sample can be obtained
rapidly, diagnostic data can be collected prior to therapeutic invention, if possible.
Critical samples
● Blood – When hypoglycemia is suspected based on symptoms and point-of-care

glucose testing, the condition should be confirmed via venous plasma glucose.
Additionally, a sample should be obtained to measure major metabolic fuels and
counterregulatory hormones when the plasma glucose is <50 mg/dL (2.8 mmol/L)
because this is the crucial step to establishing a specific etiology. If sulfonylurea
ingestion is suspected, specific toxicology studies should also be sent. (See 'Critical
samples' below.)
● Urine – The first urine voided during or immediately after the hypoglycemic event
should be collected and tested for ketones (if blood ketones cannot be measured)
and urine organic acids.
Treatment
Glucose therapy
● Conscious patient – If the child is conscious and cooperative, 15 g (or 0.2 g/kg for
infants) of rapid-acting carbohydrate should be given by mouth. This amount can be
supplied by 4 ounces of juice, a tube of glucose gel, or four glucose tablets.
Obtaining intravenous access is recommended in the event that the child's glucose
fails to respond to the oral intervention.
● Patient with altered consciousness – If the child is unconscious or not judged as

safe to take oral carbohydrates, intravenous dextrose should be administered:
• Initial bolus – 2 mL/kg of dextrose 10% (0.2 g dextrose/kg body weight) should
be given. If glucose fails to increase after 15 to 20 minutes, a repeat bolus should
be administered. Higher concentrations of dextrose are not recommended as an
initial bolus, as they frequently result in hyperglycemia with a subsequent insulin
surge, triggering further hypoglycemia. (See "Primary drugs in pediatric
resuscitation", section on 'Dextrose (glucose)'.)
• Dextrose infusion – After the initial bolus, a dextrose infusion should be started
to prevent recurrent hypoglycemia. Infants should be started on a glucose
infusion rate (GIR) of 5 to 6 mg/kg/minute (typically, dextrose 10% at maintenance
rate). Older children have lower glucose requirements and can be initially placed
on a GIR of 2 to 3 mg/kg/minute (typically, dextrose 5% at maintenance rate). The
GIR should be increased every 15 to 20 minutes, in increments of 0.5 to 1
mg/kg/minute until the patient's plasma glucose concentration is at least 70
mg/dL.
GIR = (dextrose percentage × rate of infusion [mL/hr]) ÷ (6 × weight [kg])
Glucagon — If the child's mental status is altered and intravenous access cannot be
obtained, glucagon can be used to acutely increase the plasma glucose. The
recommended dose is 0.5 mg (<25 kg) or 1 mg (>25 kg) intramuscularly.
Glucagon is only effective for patients with suspected insulin-mediated hypoglycemia. This
includes children with hyperinsulinism, surreptitious insulin administration, or
sulfonylurea ingestion [13]. Glucagon is not effective in other forms of hypoglycemia. This
effect of glucagon is useful as a diagnostic tool. (See 'Diagnostic evaluation' below.)
Monitoring — The plasma glucose should be monitored every 15 to 20 minutes until it is

>70 mg/dL (3.9 mmol/L). Thereafter, it can be checked hourly to ensure stability, and then
subsequent checks can be further spaced to every three to four hours.
EVALUATION FOR THE CAUSE OF HYPOGLYCEMIA
Overview of the causes of hypoglycemia
The disorders of hypoglycemia can be categorized by their metabolic and hormonal

profiles in response to fasting (see 'Glucose homeostasis in normal infants and children'
above). This results in four broad categories of disorders ( algorithm 1):
● Insulin-mediated disorders
● Fatty acid oxidation disorders
● Ketotic hypoglycemic disorders
● Disorders of gluconeogenesis
Specific causes within each of these categories are outlined in the table ( table 4) and
detailed in a separate topic review. (See "Causes of hypoglycemia in infants and children".)
History — The history of a child with hypoglycemia should include exploration of past
medical history (including perinatal history), details of the acute event as well as any
previous episodes, and family history.
● Age at presentation – Although there is considerable overlap, age at presentation

suggests diagnostic categories:
• Neonatal period and early infancy – Hyperinsulinism, disorders of

gluconeogenesis, most inborn errors of metabolism and panhypopituitarism
• First two years of life – Glycogen storage disorders, growth hormone or cortisol
deficiencies
• Toddlers and young children – Ingestion, idiopathic ketotic hypoglycemia,

glycogen storage disorders
• School-aged children and adolescents – Insulinoma, factitious hypoglycemia,

other ingestions
● Symptoms – Although infants and young children with hypoglycemia are frequently
asymptomatic, it is important to inquire about any symptoms of hypoglycemia prior
to the acute event. (See 'Clinical features' above.)
● Triggers – The details of the acute event should be carefully explored and should
include feeding history, concurrent illness, and medication exposure. This
information helps to narrow the differential diagnosis of possible causes.
• Duration of fasting – Details should be obtained on how long the child fasted
prior to the acute event, as well as how long the child fasts on a routine basis. A
short duration of fasting (several hours) before onset of symptoms suggests
hyperinsulinism or glycogen storage disorder type I or III. A longer duration of
fasting (overnight) suggests a different glycogen storage disorder (types 0, VI, or
IX), a hormone deficiency, a disorder of gluconeogenesis, or idiopathic ketotic
hypoglycemia.
• Specific foods – Determine whether specific foods and nutrients may have
triggered the hypoglycemic episode(s).
- Symptoms after ingestion of milk products or fructose may indicate

galactosemia or hereditary fructose intolerance, respectively.
- Unripe lychee or ackee fruit (a staple in Jamaican diets) causes severe

vomiting and hypoglycemia.
• Concurrent illness – In children with unrecognized hypoglycemic disorders, the

episodes are often triggered by illnesses that interrupt normal feeding. Thus,
further evaluation is indicated for a child presenting with hypoglycemia during a
noncritical, intercurrent illness [14]. The misperception that hypoglycemia is a
common and normal result of routine childhood illnesses leads to delays in
diagnosis and increased risk of neurologic damage. Hypoglycemia occurring
during common childhood illnesses may be a clue to an underlying hypoglycemia
disorder. For patients with critical illnesses, such as acute liver failure and sepsis,
hypoglycemia is often a direct consequence of the illness rather than evidence of
an underlying hypoglycemic disorder.
• Ingestion – The clinician must inquire about possible exposure to substances

that cause hypoglycemia, such as oral hypoglycemic agents (sulfonylureas or
meglitinides), ethanol, or beta blockers. (See "Causes of hypoglycemia in infants

and children".)
● Past medical history
• Perinatal history – A thorough perinatal history is crucial and should include the
birth weight, gestational age, and whether the child had hypoglycemia at birth or
in the neonatal period, including what type of treatment was necessary. A history
of being born large for gestational age suggests congenital hyperinsulinism or
Beckwith-Wiedemann syndrome. Intrauterine growth restriction or born small for
gestational age can result in the perinatal stress-induced form of hyperinsulinism
[15].
Results of newborn screening tests should be reviewed. Important considerations

include fatty acid oxidation disorders and galactosemia, in which hypoglycemia is
a primary manifestation; these are included in most screening programs in the
United States. Hypoglycemia may also be an associated feature in some other
inborn errors of metabolism such as defects in amino acid metabolism. (See
"Newborn screening", section on 'Implementation of screening'.)
• Prior events – It is important to explore the child's past medical history and to
review available medical records to determine whether the child had other
episodes suggestive of hypoglycemia that may have been missed or diagnosed as
another condition (eg, seizure disorder).
● Family history – Family members with a history of hypoglycemia or a monogenic

form of diabetes suggest the possibility of a familial hyperinsulinemic disorder. A
family history of Reye syndrome, unexplained infant deaths, or unexplained
hypoglycemic episodes suggest an inborn error of metabolism, particularly a fatty
acid oxidation defect. The clinician should specifically inquire whether other family
members have been diagnosed with any inborn error of metabolism (or "metabolic
disorder").
● Physical examination – A thorough examination can provide important diagnostic

clues.
• Anthropometrics – The child's weight and length or height should be measured

and plotted on an appropriate growth chart, and the child's growth trajectory
should be evaluated. Short stature or poor linear growth may indicate growth
hormone deficiency or a glycogen storage disorder. Tall stature is associated with
an overgrowth syndrome, such as Beckwith-Wiedemann syndrome or Sotos
syndrome. Poor weight gain suggests a glycogen storage disease or a disorder of
gluconeogenesis. Poor weight gain also may be caused by hypopituitarism and
adrenocorticotropic hormone (ACTH) deficiency or primary adrenal insufficiency.
Children who are underweight for age may also be at risk for idiopathic ketotic
hypoglycemia.
• Midline defects (eg, a single central incisor, optic nerve hypoplasia, cleft lip or
palate, umbilical hernia) and microphallus or undescended testicles in boys may
indicate hypopituitarism and/or growth hormone deficiency.
• Hepatomegaly is common feature of the glycogen storage disorders.
• Macroglossia, abdominal wall defects, or hemihypertrophy may indicate

Beckwith-Wiedemann syndrome [16].
• Hyperventilation may be a clue to metabolic acidosis from an inborn error of

metabolism or ingestion.
• Hyperpigmentation suggests primary adrenal insufficiency.
Diagnostic evaluation — The history and physical examination are used to develop
clinical suspicions, and the evaluation is tailored accordingly. As examples, clinical features
suggesting an accidental or toxic ingestion or a specific inborn error of metabolism should
prompt specific testing for the suspected disorder.
Critical samples — Evaluation for the majority of children presenting with hypoglycemia
will require obtaining a "critical sample" of blood and urine at the time of hypoglycemia to
measure metabolic fuels and counterregulatory hormones. These critical samples must be
obtained at the time of hypoglycemia (plasma glucose <50 mg/dL) and before treatment,
either during the initial acute episode or during a supervised diagnostic fast.
● Blood – The critical blood sample should be tested for:
• Plasma glucose
• Beta-hydroxybutyrate (BOHB)
• Comprehensive metabolic panel

• Insulin
• C-peptide
• Free fatty acids (FFAs)
• Lactate
• Ammonia
• Cortisol
• Growth hormone
• Acyl-carnitine profile
• Free and total carnitines
● Urine – The critical urine sample should be obtained at the same time and tested for
organic acids. The sample should also be tested for ketones if blood BOHB testing is
not available.
Diagnostic fast — If a critical sample is not obtained during a spontaneous episode of

hypoglycemia, a diagnostic fasting test should be performed to determine the cause of
the hypoglycemia [17].
For safety, the possibility of a fatty acid oxidation disorder should be excluded prior to
performing the diagnostic fast, by measuring plasma carnitine and acyl-carnitine
concentrations and confirming that these are normal before proceeding with the fast.
Patients with fatty acid oxidation disorders may develop potentially life-threatening
complications with prolonged fasting. (See "Causes of hypoglycemia in infants and
children", section on 'Fatty acid oxidation disorders'.)
A diagnostic fast should only be performed in an inpatient setting with close supervision
and adequate preparation. This preparation includes close review of the fasting protocol
by the clinician and nursing staff and placement of an intravenous catheter for blood-
drawing to obtain the critical sample.
● Start of test – The fast typically begins after dinner, bedtime snack, or evening feed.
● Monitoring – Obtain bedside glucose and BOHB every three hours while glucose is
>70 mg/dL (3.9 mmol/L), hourly when glucose is 60 to 70 mg/dL (3.3 to 3.9 mmol/L),
and every 30 minutes when glucose is 50 to 60 mg/dL (2.8 to 3.3 mmol/L).
● Endpoint of test – The test should be ended when any of the following conditions are
met:
• Plasma glucose is <50 mg/dL (2.8 mmol/L), or
• Bedside plasma BOHB is >2.5 mmol/L, or
• The child develops symptoms of neuroglycopenia, or
• A specific duration has been reached. Durations used at the authors' institution:
18 hours if child is <1 month old, 24 hours if 1 to 12 months, 36 hours if >1 year,
48 hours for adolescents. Shorter durations may be considered based on clinical
picture [18,19]
When any of these conditions are met, obtain the critical sample, perform a
glucagon stimulation test if the plasma glucose is <50 mg/dL, as described below,
and end the fast.
● Glucagon stimulation test – The glycemic response to glucagon provides an index of

liver glycogen reserves. A glycemic response of ≥30 mg/dL is inappropriate, indicates
excessive glycogen reserves, and provides indirect evidence of hyperinsulinism or
insulin excess [20].
This test is performed when the glucose is <50 mg/dL (2.8 mmol/L). Then, 1 mg of
glucagon is administered intravenously or subcutaneously, and then plasma glucose
is monitored every 10 minutes for a maximum of 40 minutes.
• If the plasma glucose increases by <20 mg/dL (1.1 mmol/L) during the first 20
minutes following glucagon administration, the test should be terminated and
the child fed.
• If the plasma glucose increases by ≥30 mg/dL (1.7 mmol/L) within 40 minutes
after glucagon administration, this is considered an inappropriate glycemic
response and is consistent with an insulin-mediated hypoglycemic disorder.
• If the plasma glucose increases by <30 mg/dL within 40 minutes after glucagon
administration, an insulin-mediated hypoglycemic disorder is unlikely.
Interpretation of results — The results from the critical sample obtained during an
episode of hypoglycemia (either at the time of initial presentation or during a diagnostic
fasting test) and the glucagon stimulation test are used to identify the type of
hypoglycemic disorder.
The disorders of hypoglycemia can be categorized by the levels of the metabolic fuels
(lactate, ketones, FFAs) obtained at the time of hypoglycemia ( algorithm 1). Other
results from the critical sample further refine the diagnosis and/or direct additional
testing.
Low ketones and low free fatty acids — Low ketones (BOHB) and low FFAs suggest an
insulin-mediated hypoglycemic disorder. These disorders are also characterized by a
positive glycemic response to glucagon and no acidosis (ie, bicarbonate is ≥18 mmol/L).
Insulin-mediated hypoglycemic disorders – The diagnosis of insulin-mediated

hypoglycemic disorders, of which congenital hyperinsulinism is the most common,
requires demonstrating evidence of insulin excess:
● Detectable insulin level at the time of hypoglycemia – When plasma glucose is <50
mg/dL (2.8 mmol/L), any detectable amount of insulin is abnormal. However, given
the limitations and variable sensitivity of insulin assays, a detectable insulin level is
not necessary to make the diagnosis of hyperinsulinism, and other criteria also need
to be considered [21]. Conversely, an undetectable insulin level does not rule out
hyperinsulinism. The sensitivity and specificity of a detectable plasma insulin at the
time of hypoglycemia are 82.2 and 100 percent, respectively [22]. Similarly, a C-
peptide concentration ≥0.5 ng/mL is evidence that insulin secretion is not
appropriately suppressed in response to decreasing glucose concentrations. The
sensitivity and specificity of a C-peptide plasma concentration of ≥0.5 ng/mL are 88.5
and 100 percent, respectively [22].
● Suppressed levels of BOHB and FFA – Insulin suppresses lipolysis and ketogenesis,
resulting in inappropriately low levels of BOHB and FFA at the time of hypoglycemia.
BOHB levels <1.8 mmol/L and FFA <1.7 mmol/L are consistent with insulin excess. A
suppressed BOHB concentration of <1.8 mmol/L has a sensitivity and specificity of
100 percent [22]. A suppressed plasma FFA concentration of <1.7 mmol/L has a
sensitivity and specificity of 87 and 100 percent, respectively [22].
● Glycemic response to glucagon – A rise in glucose of more than 30 mg/dL after

administration of glucagon is consistent with hyperinsulinemia because it reflects
excessive insulin action on the liver. Insulin suppresses hepatic glycogenolysis, which
leads to inappropriately high reserves of glycogen in the liver at the time of
hypoglycemia. The sensitivity and specificity of a glycemic response ≥30 mg/dL to
glucagon are 89 and 100 percent, respectively [22].
Insulin-mediated hypoglycemic disorders are listed in the table ( table 4). The insulin
level and C-peptide levels can help to distinguish some of these causes:
● Detectable insulin level with undetectable C-peptide – This combination suggests

exogenous insulin administration (eg, due to surreptitious insulin administration in
the case of medical child abuse). However, an undetectable insulin level does not
exclude this possibility, because not all laboratory assays detect the insulin analogs;
a special assay may be required to detect certain insulin analogs [23].
● Detectable insulin and C-peptide levels – This combination of findings is consistent

with hyperinsulinism, sulfonylurea ingestion (accidental or deliberate), or
insulinoma. In many cases, these causes can be distinguished by the patient's age
and other historical features. If sulfonylurea ingestion is suspected, separate
toxicology studies, including a specific screen for sulfonylureas, should be sent as
soon as possible.
(See "Causes of hypoglycemia in infants and children", section on 'Insulin-mediated

disorders'.)
Low ketones and elevated free fatty acids — Fatty acid oxidation disorders are
characterized by suppressed ketones with elevated FFAs, without acidosis ( algorithm 1)
[24]. The plasma acyl-carnitine profile helps identify the specific type of disorder. (See
"Overview of fatty acid oxidation disorders" and "Specific fatty acid oxidation disorders".)
Elevated ketones with acidemia — Elevated ketones and acidemia (bicarbonate <18
mmol/L) indicate a ketotic hypoglycemic disorder ( table 4), which may be caused by
several distinct mechanisms. Acidemia (serum TCO2 or bicarbonate <18 mmol/L) may not
be present in some cases.
● Disorders of glycogen metabolism – The hepatic glycogen storage diseases (types 0,

III, VI, and IX) are characterized by ketotic hypoglycemia (BOHB >2.5 mmol/L at the
time of hypoglycemia), hyperlipidemia, and elevated liver function tests [25]. Patients
with glycogen storage disease type III will also have increased creatine kinase levels
due to the involvement of muscle glycogen stores in this disorder, as well as

hyperlipidemia.
● Hormone deficiencies – After the newborn period, patients with deficiencies of

cortisol and growth hormone can present with ketotic hypoglycemia. However, in the
neonate, hormone deficiencies or hypopituitarism will have laboratory findings
identical to those found in hyperinsulinism (suppressed BOHB and FFA, glycemic
response to glucagon). Low cortisol and growth hormone levels in the critical sample
are not sufficient to diagnose adrenal insufficiency or growth hormone deficiency
[26]. If the critical sample has low cortisol or growth hormone concentrations, the
appropriate stimulation testing must be obtained to confirm a diagnosis of the
hormone deficiency prior to initiating treatment. A brain magnetic resonance
imaging (MRI) should also be obtained if the diagnosis of growth hormone deficiency
or hypopituitarism is made.
● Idiopathic ketotic hypoglycemia – This disorder is typically seen in toddlers

presenting with a shortened fasting tolerance and marked ketosis (BOHB >2.5
mmol/L). This is a diagnosis of exclusion; other causes of ketotic hypoglycemia must
be ruled out, including disorders of glycogen metabolism (glycogen storage
diseases) and pituitary hormone deficiencies.
● Ketone utilization defects – Markedly elevated ketones with mild hypoglycemia may
be seen in patients with ketone utilization defects. In contrast to other conditions
that present with a pattern of ketotic hypoglycemia, in ketone utilization defects,
hyperketonemia does not rapidly resolve after a feeding. These disorders are rare
and result in elevated BOHB levels in both the fasting and fed state. They include
succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency (MIM #245050), alpha-
methylacetoacetic aciduria (MIM #203750), and monocarboxylate transporter 1
(MCT1) deficiency (MIM #616095).
(See "Causes of hypoglycemia in infants and children", section on 'Ketotic

hypoglycemic disorders'.)
Elevated lactate with acidemia — Elevated lactate levels with acidemia during an
episode of hypoglycemia suggest a disorder of gluconeogenesis. These findings should
prompt further testing for the specific disorder, such as glucose-6-phosphatase deficiency
(glycogen storage disease type I) [27]. Patients with these disorders will have elevations in
their liver enzymes as well as increased levels of triglycerides and uric acid. Additionally,
administration of glucagon following a meal results in increased lactate levels with no
significant change in plasma glucose concentration. (See "Causes of hypoglycemia in
infants and children", section on 'Disorders of gluconeogenesis'.)
Additional testing — Once the general category of disorder is identified, further

diagnostic testing can be performed to identify the specific disorder. A variety of disorders
are diagnosed with genetic testing (eg, congenital hyperinsulinism, defects in
gluconeogenesis or glycogenolysis, fatty acid oxidation disorders). Further information
about identifying the specific disorder within each category is available in separate topic
reviews. (See "Causes of hypoglycemia in infants and children".)
If the diagnosis and appropriate therapy cannot be readily determined, the child should
be transferred to a center experienced with the diagnosis of hypoglycemic disorders. In
these cases, whole-exome sequencing may be considered to identify new and previously
unrecognized disorders.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links:
Hypoglycemia in infants and children" and "Society guideline links: Hypoglycemia in the
neonate".)
SUMMARY
Hypoglycemia in infants and children requires prompt recognition, definitive diagnosis,

and treatment to prevent permanent neurologic sequelae. The key steps are summarized
in a rapid overview ( table 3).
● Clinical features – Symptoms and signs of hypoglycemia include sweating, tremor,

palpitations, pallor, tachycardia, weakness, and hunger (neurogenic symptoms), as
well as lethargy, confusion, irritability, loss of consciousness, and seizure
(neuroglycopenic symptoms). Older children and adults demonstrate the Whipple
triad (symptoms consistent with hypoglycemia, low plasma glucose, and resolution
of symptoms with normalization of plasma glucose). However, symptoms in infants

and toddlers are frequently nonspecific and include irritability, lethargy, poor
feeding, cyanosis, and tremor. Infants often manifest no symptoms of hypoglycemia
until they present with a hypoglycemic seizure. (See 'Clinical features' above.)
● Definition – Hypoglycemia is defined clinically as a plasma glucose concentration

low enough to cause signs and symptoms of brain dysfunction (neuroglycopenia).
The threshold for confirming a diagnosis of hypoglycemia and for obtaining a
diagnostic sample is <50 mg/dL (2.8 mmol/L), as documented by a laboratory-quality
assay. (See 'Diagnosis of hypoglycemia' above.)
● Immediate management – Patients with confirmed or suspected hypoglycemia

should be treated promptly by administering glucose. A sample of blood should be
taken for diagnostic testing before administering the glucose, provided that it does
not delay treatment. (See 'Glucose therapy' above.)
• If the patient is fully conscious and able to drink and swallow safely, a rapidly
absorbed carbohydrate (juice, glucose tablets, glucose gel) should be given by
mouth. If the hypoglycemia does not improve within 10 to 15 minutes, parenteral
glucose must be administered.
• If the child is unconscious or not judged as safe to take oral carbohydrates,

intravenous dextrose should be administered. An initial bolus of 2 mL/kg of
dextrose 10% (ie, 0.2 g dextrose/kg body weight) should be given. After the initial
bolus, a dextrose infusion should be started to prevent recurrent hypoglycemia (
table 3). (See "Primary drugs in pediatric resuscitation", section on 'Dextrose
(glucose)'.)
● Evaluation for the cause of hypoglycemia
• Evaluation of hypoglycemia requires obtaining a "critical sample," which is a

measurement of the hormones and fuels involved in glucose metabolism at the
time of hypoglycemia (a plasma glucose <50 mg/dL). This sample can be obtained
either during the initial acute episode, if the child's mental status is normal, or
during a supervised diagnostic fast. (See 'Diagnostic evaluation' above.)
• The results from the critical sample obtained during an episode of hypoglycemia
(either at the time of initial presentation or during a diagnostic fasting test) and
the glucagon stimulation test are used to identify the type of hypoglycemic
disorder ( table 4). Hypoglycemic disorders can be categorized by the levels of
the metabolic fuels (lactate, ketones, free fatty acids [FFAs]) obtained at the time
of hypoglycemia ( algorithm 1). Other results from the critical sample further
refine the diagnosis and/or direct additional testing. (See 'Interpretation of
results' above.)
ACKNOWLEDGMENTS
The editorial staff at UpToDate would like to acknowledge Agneta Sunehag, MD, PhD, and
Morey W Haymond, MD, who contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Terms of Use.
REFERENCES
1. Lord K, Radcliffe J, Gallagher PR, et al. High Risk of Diabetes and Neurobehavioral
Deficits in Individuals With Surgically Treated Hyperinsulinism. J Clin Endocrinol
Metab 2015; 100:4133.
2. Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest 2007;
117:868.
3. Stanley C, Baker L. Hypoglycemia. In: Core Textbook of Pediatrics, Kaye R, Oski FA, Bar
ness LA (Eds), Lippincott, Philadelphia 1978. p.280.
4. Cahill GF Jr, Herrera MG, Morgan AP, et al. Hormone-fuel interrelationships during
fasting. J Clin Invest 1966; 45:1751.
5. Owen OE, Morgan AP, Kemp HG, et al. Brain metabolism during fasting. J Clin Invest
1967; 46:1589.
6. Haymond MW, Karl IE, Clarke WL, et al. Differences in circulating gluconeogenic
substrates during short-term fasting in men, women, and children. Metabolism 1982;
31:33.
7. Cryer PE. Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N
Engl J Med 2004; 350:2272.
8. Hussain K, Bryan J, Christesen HT, et al. Serum glucagon counterregulatory hormonal
response to hypoglycemia is blunted in congenital hyperinsulinism. Diabetes 2005;

54:2946.
9. Thornton PS, Stanley CA, De Leon DD, et al. Recommendations from the Pediatric
Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in
Neonates, Infants, and Children. J Pediatr 2015; 167:238.
10. Stanley CA, Rozance PJ, Thornton PS, et al. Re-evaluating "transitional neonatal
hypoglycemia": mechanism and implications for management. J Pediatr 2015;
166:1520.
11. CORNBLATH M, REISNER SH. Blood glucose in the neonate and its clinical significance.
N Engl J Med 1965; 273:378.
12. Harris DL, Weston PJ, Gamble GD, Harding JE. Glucose Profiles in Healthy Term Infants
in the First 5 Days: The Glucose in Well Babies (GLOW) Study. J Pediatr 2020; 223:34.
13. WHITEHOUSE FW, BRYAN HG. Glucagon for treatment of insulin hypoglycemia: its use
in the patient with diabetes. Am Pract Dig Treat 1959; 10:1326.
14. White K, Truong L, Aaron K, et al. The Incidence and Etiology of Previously
Undiagnosed Hypoglycemic Disorders in the Emergency Department. Pediatr Emerg
Care 2020; 36:322.
15. Collins JE, Leonard JV. Hyperinsulinism in asphyxiated and small-for-dates infants with
hypoglycaemia. Lancet 1984; 2:311.
16. Kalish JM, Boodhansingh KE, Bhatti TR, et al. Congenital hyperinsulinism in children
with paternal 11p uniparental isodisomy and Beckwith-Wiedemann syndrome. J Med
Genet 2016; 53:53.
17. Morris AA, Thekekara A, Wilks Z, et al. Evaluation of fasts for investigating
hypoglycaemia or suspected metabolic disease. Arch Dis Child 1996; 75:115.
18. van Veen MR, van Hasselt PM, de Sain-van der Velden MG, et al. Metabolic profiles in
children during fasting. Pediatrics 2011; 127:e1021.
19. Chaussain JL, Georges P, Calzada L, Job JC. Glycemic response to 24-hour fast in
normal children: III. Influence of age. J Pediatr 1977; 91:711.
20. Finegold DN, Stanley CA, Baker L. Glycemic response to glucagon during fasting
hypoglycemia: an aid in the diagnosis of hyperinsulinism. J Pediatr 1980; 96:257.
21. De León DD, Stanley CA. Determination of insulin for the diagnosis of
hyperinsulinemic hypoglycemia. Best Pract Res Clin Endocrinol Metab 2013; 27:763.
22. Ferrara C, Patel P, Becker S, et al. Biomarkers of Insulin for the Diagnosis of
Hyperinsulinemic Hypoglycemia in Infants and Children. J Pediatr 2016; 168:212.
23. Green RP, Hollander AS, Thevis M, et al. Detection of surreptitious administration of
analog insulin to an 8-week-old infant. Pediatrics 2010; 125:e1236.
24. Stanley C, Bennett MJ. Disorders of mitochondrial fally acid beta-oxidation. In: Nelson
Textbook of Pediatrics, 18th ed, R, Behrman R, Jenson H, et al (Eds), Saunders, 2007. p
.567.
25. Fernandes J, Pikaar NA. Ketosis in hepatic glycogenosis. Arch Dis Child 1972; 47:41.
26. Kelly A, Tang R, Becker S, Stanley CA. Poor specificity of low growth hormone and
cortisol levels during fasting hypoglycemia for the diagnoses of growth hormone
deficiency and adrenal insufficiency. Pediatrics 2008; 122:e522.
27. Weinstein DA, Steuerwald U, De Souza CFM, Derks TGJ. Inborn Errors of Metabolism
with Hypoglycemia: Glycogen Storage Diseases and Inherited Disorders of
Gluconeogenesis. Pediatr Clin North Am 2018; 65:247.
Topic 5805 Version 27.0
GRAPHICS
Categorization of hypoglycemic disorders based on biochemical profile
Schematic representation of the biochemical profile obtained on the critical sample obtained during an
episode of hypoglycemia. The biochemical profile helps to identify the pathophysiologic category of the
underlying hypoglycemic disorder.
FFA: free fatty acid; MCADD: medium-chain acyl-CoA dehydrogenase deficiency; VLCADD: very-long-chain
acyl-CoA dehydrogenase deficiency; GSD: glycogen storage disease; F-1,6-Pase: fructose-1,6-
bisphosphatase; PC: pyruvate carboxylase.
* Some ketotic hypoglycemic disorders may not have detectable acidemia, especially idiopathic ketotic
hypoglycemia, growth hormone deficiency, and cortisol deficiency.
Original figure modified for this publication. From: Thornton PS, Stanley CA, De Leon DD, et al. Recommendations from the
Pediatric Endocrine Society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J
Pediatr 2015; 167:238. Illustration used with the permission of Elsevier Inc. All rights reserved.
Graphic 121836 Version 2.0
Hormonal control of fasting
Glycogenolysis Gluconeogenesis Lipolysis Ketogenesis
Insulin ↓ ↓ ↓ ↓
Glucagon ↑ ↑ ↑
Epinephrine ↑ ↑ ↑
Cortisol ↑
Growth ↑
hormone
↓: decreased; ↑: increased.
Neonates at increased risk for hypoglycemia
Neonates at increased risk for hypoglycemia (require glucose screening):
Symptoms of hypoglycemia
Large for gestational age (even without maternal diabetes)
Perinatal stress
Birth asphyxia/ischemia
Cesarean delivery for fetal distress
Maternal preeclampsia/eclampsia or hypertension
Intrauterine growth restriction or small for gestational age
Meconium aspiration syndrome, erythroblastosis fetalis, polycythemia, hypothermia
Premature or postmature delivery
Infant of diabetic mother
Family history of a genetic form of hypoglycemia
Congenital syndromes (eg, Beckwith-Wiedemann syndrome)
Abnormal physical features (eg, midline facial malformations, microphallus)
Neonates at risk for persistent hypoglycemia (require more extensive

evaluation):
Severe hypoglycemia (eg, episode of symptomatic hypoglycemia)
Inability to consistently maintain preprandial plasma glucose >50 mg/dL up to 48 hours

of life and >60 mg/dL after 48 hours of life
Family history of a genetic form of hypoglycemia
Congenital syndromes (eg, Beckwith-Wiedemann syndrome)
Original table modified for this publication. From: Thornton PS, Stanley CA, De Leon DD, et al. Recommendations
from the Pediatric Endocrine Society for evaluation and management of persistent hypoglycemia in neonates,
infants, and children. J Pediatr 2015; 167:238. Table used with the permission of Elsevier Inc. All rights reserved.
Rapid overview for diagnosis and treatment of hypoglycemia in

adolescents and children (other than neonates) in the Emergency
Department
Clinical features
Any patient with acute lethargy or coma should have an immediate measurement of blood
glucose to determine if hypoglycemia is a possible cause
Other findings of hypoglycemia are nonspecific* and vary by age:
Infants Older children and adolescents
Irritability Neurogenic (autonomic) Neuroglycopenic response

Lethargy response Irritability
Jitteriness Sweating Confusion
Feeding problems Tachycardia Uncharacteristic
Hypothermia Palpitations behavior
Hypotonia Tremor Weakness
Tachypnea Nervousness Lethargy
Cyanosis Hunger Loss of consciousness
Apnea Paresthesias Seizures
Seizures Pallor Coma
Occasionally, transient
focal neurologic
deficits
Diagnosis
Obtain rapid bedside point-of-care glucose concentration (and beta-hydroxybutyrate, if

available as a point-of-care measurement)
Confirm the presence of hypoglycemia with a plasma glucose measurement (drawn close
in time to the point-of-care sample)
Treat, as outlined below, if the bedside value is low (<70 mg/dL [3.89 mmol/L]) in
symptomatic patients
For all infants and young children who are not being treated for diabetes mellitus or do
not have a known cause for hypoglycemia, obtain a blood sample for additional
diagnostic studies prior to glucose administration, if possible, and collect the first voided
urine after the hypoglycemic event. ¶
Treatment
Do not delay treatment if symptomatic hypoglycemia is suspected. However, every
reasonable effort should be made to obtain a rapid plasma glucose measurement

(fingerstick or point-of-care device) prior to administering glucose.
Give glucose based upon the patient's level of consciousness and ability to swallow
safely (ie, alert enough to do so and with intact gag reflex) as follows:
Conscious and able to drink and swallow safely:
Administer 0.3 g/kg (10 to 20 g) of a rapidly-absorbed carbohydrate. May repeat

in 10 to 15 minutes.
Options include any one of the following:
Glucose tablets (5 g per tablet)

Glucose gel (15 g per tube)
Sweetened fruit juice: 12 g carbohydrate per 4 oz (120 mL)
Regular soda (not diet): 18 g carbohydrate per 6 oz (180 mL)
Honey: 17 g carbohydrate per 1 tablespoon (15 mL)
Table sugar (granulated sugar): 12.5 g sugar per 1 tablespoon
Altered mental status, unable to swallow, or does not respond to oral glucose
administration within 15 minutes:
Give an initial IV bolus of glucose of 0.25 to 0.5 g/kg of dextrose (maximum

single dose 25 g). Δ The volume and concentration of glucose bolus is infused
slowly at 2 to 3 mL per minute and based upon age:
Infants and children up to 12 years: 2.5 to 5 mL/kg of 10% dextrose solution

(D10W), or 1 to 2 mL/kg of 25% dextrose (D25W). D10W is typically used in
infants and children <5 years of age. (10% dextrose is 100 mg/mL; 25%
dextrose is 250 mg/mL.)
Adolescents ≥12 years: 1 to 2 mL/kg of D25W
Unable to receive oral glucose and unable to obtain IV access:
Give glucagon 0.5 mg (for <25 kg body weight) or 1 mg (for ≥25 kg body
weight) IM or SQ (maximum dose 1 mg): ◊
Perform blood glucose monitoring every 10 to 15 minutes as the effects of

glucagon may be transient
Establish vascular access as soon as possible; if unable to achieve access and
hypoglycemia persists or is recurrent, ensure the airway is protected and, if
not, secure it with rapid sequence intubation. Then place a nasogastric tube
and administer 0.2 to 0.25 g/kg dextrose using volume and concentration
guidance for IV administration above.
After initial hypoglycemia is reversed, provide additional glucose and treatment based
upon suspected etiology:
For patients with type 1 diabetes mellitus: Give a normal diet; initiate IV dextrose-
containing fluids if intake is inadequate.
For patients with an underlying hypoglycemic disorder or with an unknown cause of
hypoglycemia: Administer an intravenous infusion of dextrose 10%:

For infants, start with initial glucose infusion rate (GIR) of 5 to 6 mg/kg/minute
For older children, start with GIR of 2 to 3 mg/kg/minute
Calculation to convert target GIR to infusion rate:
Rate of dextrose infusion (mL/hr) = GIR (mg/kg/minute) × 6 × weight (kg) ÷
dextrose percentage of fluid (eg, 5 for 5% dextrose [D5W] or 10 for D10W)
Titrate infusion to maintain plasma glucose in a safe and appropriate range (70 to
120 mg/dL [3.89 to 8.33 mmol/L]).
Patients who have ingested a long-acting hypoglycemia agent such as a sulfonylurea
may require prolonged treatment until the effect wears off. Selected patients may
also warrant treatment with octreotide. (Refer to UpToDate topic on sulfonylurea
poisoning.)
Measure a rapid plasma glucose 15 to 30 minutes after the initial IV glucose bolus and
then monitor every 30 to 60 minutes until stable (minimum of four hours) to ensure that
plasma glucose concentration is maintained in the normal range (>70 to 100 mg/dL
[>3.89 to 5.55 mmol/L])
Obtain pediatric endocrinology consultation for patients with persistent hypoglycemia
and for hypoglycemia of unknown cause
Obtain medical toxicology consultation for patients with ingestion of oral hypoglycemic
agents by calling a regional poison control center. §
Admit the following patients:
Cannot maintain normoglycemia with oral intake
Hypoglycemia of unknown cause
Ingestion of long-acting hypoglycemic agents
Recurrent hypoglycemia during the period of observation
IV: intravenous; IM: intramuscular; SQ: subcutaneous; D10W: 10% dextrose in water; D25W:
25% dextrose in water; D50W: 50% dextrose in water; GIR: glucose infusion rate.
* These findings may also occur in infants with sepsis, congenital heart disease, respiratory
distress syndrome, intraventricular hemorrhage, other metabolic disorders, and in children
and adolescents with a variety of underlying conditions.
¶ Specific laboratory studies to obtain in children include blood samples for glucose, insulin, C-
peptide, beta-hydroxybutyrate, lactate (free flowing blood must be obtained without a
tourniquet), plasma acylcarnitines, free fatty acids, growth hormone, and cortisol.
Δ Higher doses of glucose (eg, 0.5 to 1 g/kg [5 to 10 mL/kg of 10% dextrose in water or 2 to 4
mL/kg of 25% dextrose in water]) is recommended by the Pediatric Advanced Life Support
course and may be needed to correct hypoglycemia caused by excess insulin administration or
sulfonylurea ingestion. (For more detail, refer to UpToDate topic on sulfonylurea agent
poisoning.)
◊ Glucagon will reverse hypoglycemia caused by excess endogenous or exogenous insulin
and will not be effective in patients with inadequate glycogen stores (prolonged fasting),
ketotic hypoglycemia, or are unable to mobilize glycogen (glycogen storage diseases). Of note,
children may exhaust their glycogen stores in as little as 12 hours. Other conditions in which
glycogen cannot be effectively mobilized include ethanol intoxication in children, adrenal
insufficiency, and certain inborn errors of metabolism (eg, a disorder of glycogen synthesis
and glycogen storage diseases).
§ To access a regional poison control center in the United States, call 1-800-222-1222. Contact
information for poison centers around the world is available at the following website:
https://www.liquidglassnanotech.com/poison-emergency-center-contact-numbers/.
Causes of hypoglycemia in infants and children
MIM
Disorder Typical age group
#
Insulin-mediated
Hyperinsulinism
Congenital Neonatal, infancy
K ATP hyperinsulinism 256450,

601820
GLUD1 hyperinsulinism 606762
GCK hyperinsulinism 602485
Perinatal stress-induced Neonatal

hyperinsulinism
Syndromic hyperinsulinism
Beckwith-Wiedemann syndrome 130650 Neonatal, infancy
Kabuki syndrome 147920 Neonatal, infancy
Insulinoma
Associated with MEN1 131100 Adolescence
Factitious hypoglycemia Any age
Congenital disorders of glycosylation
Phosphomannomutase 2 deficiency 212065 Infancy, childhood
Phosphoglucomutase 1 deficiency 614921 Any age
Mannosephosphate isomerase 602579 Infancy

deficiency
Fatty acid oxidation disorders
Medium-chain acyl-CoA dehydrogenase 201450 Infancy
20+ other disorders All ages
Ketotic hypoglycemia
Disorders of glycogen metabolism
Glycogen storage disease type 0 240600 Early childhood
Glycogen storage disease type III 232400 Infancy
Glycogen storage disease type VI 232700 Early childhood
Glycogen storage disease type IX 306000 Early childhood
Hormone deficiencies
Growth hormone deficiency Infancy, early childhood
Cortisol deficiency Childhood
Ketone utilization defects 245050, Early childhood

203750,
616095
Idiopathic ketotic hypoglycemia Early childhood
Disorders of gluconeogenesis
Glycogen storage type I* 232200 Infancy
Fructose-1,6-bisphosphatase deficiency 229700 Infancy, early childhood
Pyruvate carboxylase deficiency 266150 Infancy
PEPCK deficiency 261650 Infancy
Galactosemia 230400; Infancy

others
Hereditary fructose intolerance 229600 Infancy, childhood
Other causes
Ingestions Early childhood, all ages
Oral hypoglycemic
Ethanol Adolescence
Salicylates
Beta blockers
Pentamidine
6-mercaptopurine
Ackee/lychee fruit
Liver failure All ages
Sepsis Infancy, childhood
MIM: Mendelian Inheritance in Man database; K ATP : ATP-sensitive potassium channel; GLUD1:
glutamate dehydrogenase 1 gene; GCK: glucokinase gene; MEN1: multiple endocrine
neoplasia type 1; PEPCK: phosphoenolpyruvate carboxykinase.
* Also, disorders of glycogen metabolism.
Contributor Disclosures
Diva D De Leon-Crutchlow, MD, MSCE Patent Holder: Exendin-9-39 [Hyperinsulinism].
Grant/Research/Clinical Trial Support: Zealand Pharma [Hyperinsulinism]; Crinetics Pharmaceuticals
[Hyperinsulinism]; Tiburio [Hyperinsulinism]; Hanmi Pharmaceuticals [Hyperinsulinism]; Rezolute
[Hyperinsulinism]; Ultragenyx [Glycogen storage disease]. Consultant/Advisory Boards: Hanmi
[Hyperinsulinism]; Poxel [Hyperinsulinism]; Crinetics [Hyperinsulinism]; Poxel
Pharma[Hyperinsulinism]; Heptares Therapeutics [Hyperinsulinism]; Eiger Pharma [Hyperinsulinism];
Ultragenyx [Glycogen storage disease]. All of the relevant financial relationships listed have been
mitigated. Katherine Lord, MD No relevant financial relationship(s) with ineligible companies to
disclose. Joseph I Wolfsdorf, MD, BCh No relevant financial relationship(s) with ineligible companies to
disclose. Alison G Hoppin, MD No relevant financial relationship(s) with ineligible companies to
disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

Approach To Hypoglycemia in Infants and Children - UpToDate

Uploaded by

Copyright:

Available Formats

Approach To Hypoglycemia in Infants and Children - UpToDate

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Approach To Hypoglycemia in Infants and Children - UpToDate

Uploaded by

Copyright:

Available Formats

Approach to hypoglycemia in infants and children - UpToDate 24/04/22 12.

Official reprint from UpToDate®

The differential of hypoglycemic disorders is broad, and it is essential to have a systematic

● (See "Causes of hypoglycemia in infants and children".)

● (See "Pathogenesis, clinical presentation, and diagnosis of congenital

GLUCOSE HOMEOSTASIS IN NORMAL INFANTS AND CHILDREN

Symptoms of hypoglycemia can be divided into neurogenic and neuroglycopenic

● Neurogenic (autonomic) symptoms are caused by the sympathetic nervous system's

● Neuroglycopenic symptoms result from insufficient supply of glucose to the brain,

● Older children and adults – Hypoglycemia in these age groups typically

• Symptoms and signs consistent with hypoglycemia

INDICATIONS FOR EVALUATION

In 2015, the Pediatric Endocrine Society, through a committee composed of pediatric

Hypoglycemia is defined as a plasma glucose concentration low enough to cause signs

period of "transitional" hypoglycemia during the first 48 to 72 hours of life. A study of

The immediate management of a child with hypoglycemia involves rapid normalization of

● Blood – When hypoglycemia is suspected based on symptoms and point-of-care

● Patient with altered consciousness – If the child is unconscious or not judged as

GIR = (dextrose percentage × rate of infusion [mL/hr]) ÷ (6 × weight [kg])

Monitoring — The plasma glucose should be monitored every 15 to 20 minutes until it is

EVALUATION FOR THE CAUSE OF HYPOGLYCEMIA

Overview of the causes of hypoglycemia

The disorders of hypoglycemia can be categorized by their metabolic and hormonal

● Age at presentation – Although there is considerable overlap, age at presentation

• Neonatal period and early infancy – Hyperinsulinism, disorders of

• Toddlers and young children – Ingestion, idiopathic ketotic hypoglycemia,

• School-aged children and adolescents – Insulinoma, factitious hypoglycemia,

- Symptoms after ingestion of milk products or fructose may indicate

- Unripe lychee or ackee fruit (a staple in Jamaican diets) causes severe

• Concurrent illness – In children with unrecognized hypoglycemic disorders, the

• Ingestion – The clinician must inquire about possible exposure to substances

meglitinides), ethanol, or beta blockers. (See "Causes of hypoglycemia in infants

● Past medical history

Results of newborn screening tests should be reviewed. Important considerations

● Family history – Family members with a history of hypoglycemia or a monogenic

● Physical examination – A thorough examination can provide important diagnostic

• Anthropometrics – The child's weight and length or height should be measured

• Hepatomegaly is common feature of the glycogen storage disorders.

• Macroglossia, abdominal wall defects, or hemihypertrophy may indicate

• Hyperventilation may be a clue to metabolic acidosis from an inborn error of

• Hyperpigmentation suggests primary adrenal insufficiency.

● Blood – The critical blood sample should be tested for:

• Comprehensive metabolic panel

Diagnostic fast — If a critical sample is not obtained during a spontaneous episode of

• Plasma glucose is <50 mg/dL (2.8 mmol/L), or

• Bedside plasma BOHB is >2.5 mmol/L, or

• The child develops symptoms of neuroglycopenia, or

● Glucagon stimulation test – The glycemic response to glucagon provides an index of

Insulin-mediated hypoglycemic disorders – The diagnosis of insulin-mediated

● Glycemic response to glucagon – A rise in glucose of more than 30 mg/dL after

● Detectable insulin level with undetectable C-peptide – This combination suggests

● Detectable insulin and C-peptide levels – This combination of findings is consistent

(See "Causes of hypoglycemia in infants and children", section on 'Insulin-mediated

● Disorders of glycogen metabolism – The hepatic glycogen storage diseases (types 0,

due to the involvement of muscle glycogen stores in this disorder, as well as

● Hormone deficiencies – After the newborn period, patients with deficiencies of

● Idiopathic ketotic hypoglycemia – This disorder is typically seen in toddlers

(See "Causes of hypoglycemia in infants and children", section on 'Ketotic