Presentation

1. APPROACH TO HYPOGLYCEMIA
IN CHILDHOOD
DR. RAVIKUMAR S
DEPT OF PEDIATRICS
MGMCRI

2. Introduction
• Glucose plays a very important role in brain metabolism, not only as a
major metabolic fuel, but also as a precursor of essential proteins and
lipids in the developing brain.
• Acute Hypoglycemia is an important cause of morbidity & mortality in
acutely ill children, early recognition & treatment is critical.
• Operational Definition of Hypoglycemia:
• For neonates <40 mg/dL
• For older Infants & children < 50 mg/dL
• For SAM <54 mg/dL

3. Glucose Homeostasis

4. Pathophysiology
• Our body stores energy as carbohydrate (glycogen) and fat (triglycerides)
• During fasting, the body institutes a number of catabolic responses to
maintain the blood glucose level mediated via suppression of insulin and
release of glucagon, cortisol and growth hormone.
• These include:
a. Catabolism of glycogen to release free glucose (glycogenolysis)
b. Production of glucose from protein stores (gluconeogenesis)
c. Catabolism of triglycerides (lipolysis) through fatty acid beta-oxidation to
generate energy and ketones which can be glucose-sparing

5. Clinical Features
 Features of Sympathetic Overactivity :
• Anxiety
• Perspiration
• Palpitations
• Pallor
• Tremulousness
 Due to release of adrenaline
 Usually seen with rapid decline in blood glucose.

6. Clinical Features
 Neuroglycopenic Symptoms:
• Headache
• Mental confusion
• Visual disturbances
 Due to decreased cerebral glucose utilization
 Seen with slow decline in blood glucose or in prolonged
hypoglycemia.

7. Clinical Examination
General :
• Macrosomia/accelerated growth – Hyperinsulinism
• Obesity, truncal obesity with thin limbs – GSD
• Dysmorphic features : macroglossia, ear creases, overgrowth, hemi
hypertrophy – Beckwith wiedemann syndrome.
• Cherubic appearance, mid facial hypoplasia, cleft lip/palate in
GHD/hypopituitarism – GHD/hypopituitarism
• Midline defects can be associated with hypothalamic pituitary
insufficiency.

8. Clinical Examination
Skin:
• Hyperpigmentation – Primary adrenal insufficiency
• Vitiligo – Auto immune disease
CVS :
• Tachycardia/ Bradycardia – Cardiac failure, cardiomyopathy,
Administration of beta-blocker
Abdominal:
• Hepatocellular dysfunction with jaundice +/- : Galactosemia
• Hepatomegaly : GSD
Neurodevelopment/Neuromuscular:
• Neuropathy – Long chain FAO defects
• Developmental delay – Metabolic disorders.

9. Etiology
1) Endocrine Causes :
• PHHI (Persistent Hyperinsulinemic Hypoglycemia of Infancy)
• Pan-hypopituitarism, Isolated GH deficiency
• ACTH deficiency, Addison Disease
• Epinephrine Deficiency

10. Etiology
2) Metabolic Causes
a) Glycogenolysis & Gluconeogenesis Disorders :
• GSD types 1,3,6,9,0
• Fructose 1,6 diphosphatase deficiency
• Pyruvate Carboxylase Deficiency
• Galactosemia
• Hereditary Fructose deficiency
b) Fatty acid oxidation disorders:
b) Primary or Secondary Carnitine deficiency
c) Long/Medium chain acyl co-A dehydrogenase deficiency

11. Etiology
c) Amino acid & organic acid disorders:
• MSUD
• Glutaric Aciduria
• Tyrosinosis
• Methyl Melanoic Acidemia
3) Systemic Disorders:
• Severe Sepsis
• Malnutrition
• Neoplasm Secreting IGF -2
• Excessive Insulin therapy in Type1 DM

12. PHHI
• It can be due to either diffuse or focal beta cell hyperplasia, of which the
focal type has better prognosis.
• Mutation in the genes that prevent K-ATP channel from being open, results
in increased insulin secretion.
• Hyperinsulinemic hyperplasia is also seen in 50% Beckwith-wiedemann
syndrome
• In children >5 yrs it is usually due to islet cell adenomas which is associated
with hyperparathyroidism & pituitary tumours as a part of MEN 1

13. Ketotic Hypoglycemia
• It is the most common form of childhood hypoglycemia.
• Often presents with episodes of hypoglycemia in early morning in children
between 1 and half to 5 years of age.
• Usually undergoes spontaneous remission by the age of 8-9 years.
• Ketotic Hypoglycemia is due to defect in protein catabolism, oxidative
deamination of amino acids, transamination, alanine synthesis or alanine
efflux from muscle.
• These children have marked reduced plasma alanine concentration after
an overnight fast.

14. Investigation
• First step – To determine underlying etiology
• Critical Sample :
• Must be taken at the time of Clinically manifested hypoglycemia, before
giving glucose.
• Which includes simultaneous measurement of
– Glucose
– ABG/Lactate
– Serum Insulin, Cortisol, FFA, GH
– Urine Ketones

15. Algorithmic Approach
Recurrent/Persistent
Hypoglycemia
Urine NGRS Positive
Galactosemia
Hereditary Fructose
intolerance
CRITICAL SAMPLE
Acidosis
Present
Acidosis
Absent
High Lactate
Urine Ketone +/-
Ketone Present
Lactate +/-
GSD Type 1
Organic Acidemias
IEM
GH or Cortisol
Deficiency
No Ketone and
Normal/↓ FFA
No Ketone but
↑ FFA
PHHI
FAO Defects

16. Management
Treatment of Acute Hypoglycemic Episode in Older Children:
• After taking Critical sample, Immediately administer 10% Dextrose
2 to 5ml/kg IV bolus stat or 25% Dextrose 2ml/kg IV bolus stat (Only
in central line).
• To recheck CBG after correction.
• If BSL still low, then to start Glucose Infusion Rate accordingly.
• Central venous access should be established when the strength of
dextrose solution is more than 12.5%
• Attempts should be made to gradually taper GIR and start on oral
feeds.

17. Management
Treatment of Hyperinsulinemia
Medical:
 Diazoxide 5-15mg/kg/day in 2 div doses for atleast 5 days
• Adverse effects include Edema, Electroltye imbalance, Hirsutism, Hypotension
on prolong use.
• Addition of Thiazide helps in reducing the edema & electrolyte disturbance.
 Somatostatin analogs like Octreotide is used as a second line therapy
• Administered 5-25 mcg/kg/day in 2 div doses S.C
• Adverse effects include poor growth, Localized Pain at the Inj site, Hepatic
dysfunction

18. Management
• Long term medical therapy without surgical intervention maybe tried if
blood glucose is maintained in the normal range.
Surgical:
• In children who are refractory to medical management, subtotal or focal
Pancreatectomy may be necessary.
• Total Pancreatectomy is not advocated due to risks of surgery, permanent
Diabetes mellitus & Exocrine pancreatic insufficiency.

19. Management
Treatment of Ketotic Hypoglycemia:
• Frequent feedings with high protein and carbohydrate diet.
• During intercurrent illness, urine ketones should be monitored.
• If the oral intake is poor, IVF must be started.
• In children with FAO defect : Carnitine Supplements
• In Phosphoenol pyruvate carboxykinase deficiency, avoidance of periods
of fasting & frequent feedings rich in carbohydrate is helpful (glycogen
synthesis & breakdown are intact)
• In GSD , frequent feeds including nocturnal feeds is recommended.
• Use of corn starch helps in maintaining blood glucose for longer periods &
decreasing the episodes of hypoglycaemia.

20. Prognosis
• Prolonged/Recurrent and severe symptomatic hypoglycaemia
is associated with longterm neurologic sequel and intellectual
disability, visual defects, motor defecits manifesting as
spasticity or ataxia, seizure disorder.
• Hence early detection and prompt management is essential

21. Thank you