This document discusses hypoglycemia in infants and children. It begins by defining hypoglycemia and outlining the typical physiological response to fasting in infants and children. It then discusses the key hormones involved in regulating blood glucose levels, including insulin and counterregulatory hormones. The remainder of the document outlines various causes of hypoglycemia in neonates and children, including defects in glycogen storage and release, gluconeogenesis, and inadequate counterregulatory hormone responses. It emphasizes that hypoglycemia occurs when endogenous glucose production cannot meet energy demands during fasting periods.

1. ADMISSIONS ROUND
24/7/18
DR. BN RAVINDRA
JUNIOR RESIDENT

2. Objectives
Definition and clinical significance of hypoglycemias.
Approach to a child with recurrent hypoglycemias.
Brief overview of persistent hyperinsulinemic hypoglycemia and treatment
modalities.
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3. DEMOGRAPHIC DETAILS:
S, 6mon, First born, Mch, R/o Nayagaon, Chandigarh
DOA: 11/7/18
Chief complaints: Abnormal body movements with uprolling of eyeballs with bluish
discolouration of lips
H/o Presenting illness:
Abnormal body movements with uprolling of eyeballs with bluish discolouration of lips for few
minutes at 10:30 AM f/b LOC for 5 min.
h/o Lethargy the previous day in the morning f/b vomiting of ingested milk at 11:00 PM
Time of last meal was approximately 8 hours before the onset of seizure
h/o LM+ 5-6 ep/day 5 days before
No h/o fever

4. Antenatal h/o:
Booked and supervised with regular antenatal checkups in sector-22 hospital
Antenatal USG- told to be normal
No h/o IUGR/Polyhydramnios
No h/o high BP and high blood sugar records
Received Tab. Udiliv for IHCP for 2 weeks before delivery
Birth h/o:
36+6 wk, AGA (2.63 kg), NVD (PGI), CIAB
Baby was roomed in with mother and BF was initiated within 2 HOL
No h/o hospital admission postnatally
No documented hypoglycemias during early neonatal period.

5. Family h/o:
No h/o similar complaint in other family members
No h/o seizures in the family
H/o of HTN and type 2 DM in the maternal grandfather+
Diet h/o:
EBF from birth to 40 days of life f/b formula feeding + BF for 2 months f/b
cows milk+BF (undiluted bottle feeding ) till now.
Weaning started at 6th month with dal water and fruits (watermelon and
mangoes, litchi etc.,)

6. Immunisation h/o:
Received vaccination according to NIS till date.
No optional vaccinations received

7. Vitals:
RR: 24/min
HR: 96/min
Temp.: 98.8 F
BP: 86/54 mm of Hg
CP/PP: ++/++
CFT: 2 sec
Spo2: 97% (Room air)
Anthropometry:
Weight: 7.29 kg (3rd-50th centile)
Length: 64.5 cm (3rd-50th centile)
HC: 45 cm (50th – 97th centile)
Examination:

8. General examination:
No Dysmorphism
No midline defects/chubby appearance
No hyperpigmentation/ambiguous genitalia
No hemihypertrophy/protruding tongue
No pallor/icterus/clubbing/cyanosis/LNP/edema

9. Systemic examination:
CNS: HMF: Good state to state variability
Cranial nerves: Normal
Motor: Axial and appendicular tone- Normal
DTR’s: Normal
Chest: NVBS+, No added sounds
CVS: S1S2+, No murmur
P/A: Soft, BS+, No hepatosplenomegaly

10. Child received in emergency GMSH – 16 – was lethargic and
admission RBS was low
Subsequently started on GIR – 6mg/kg/min
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11. Data base:
Late PT/AGA/Boy/ developmentally normal/previously well
Born to a primigravida mother with h/o IHCP in 3rd trimester
Presented with symptomatic hypoglycemia i/f/o seizures at 6
months of life following a GI illness with normal systemic
examination
Provisional diagnosis:- First episode hypoglycemia -
?secondary to prolonged fasting.

12. Investigations:
CBC 11/7/18
Hb 10.2
TLC 8000
DLC 30/52/08/10
Platelet count 3.34

13. SERFT 11/7/18
B.Urea 26
S. creatinine 0.2
Na+ 140
K+ 5.2
14/7/18 - Urine routine exam.: Normal

14. During hospital admission – baby sensorium improved rapidly
following IV fluid administration
Maximum GIR required was 6mg/kg/min
IV fluids were tapered on day 2 of hospital admission
Immediately after tapering of IVF – baby had recurrence of
hypoglycemia
Critical sampling was done during hypoglycemia.
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15. Urine ketones: Negative
Urine for non glucose reducing substances +ve
ABG 13/7/18
pH 7.45
Pco2 33.7
Po2 91.0
Hco3- 22.9
Lactate 0.90

16. Parameters Patient Normal range
S. Cortisol 75 mmol/L 50-230 mmol/L
S. Insulin 24 µU/ml 0-25 µU/ml
S. Calcium 10.5 mg/dl 9.0-11.0 mg/dl

17. Hypoglycaemias
Whole blood sugar <55mg/dl (10-15% higher for serum/plasma)
Importance : Acute complications / long term Neurologic sequelae
Single isolated episodes are unlikely to have significant sequelae
Recurrent / persistent hypoglycemia – likely to cause significant CNS
sequelae.
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18. 18
Hypoglycaemias – The physiology

19. Symptoms of Hypoglycemia
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Neurogenic – Due to activation of
autonomic nervous system
Neuroglycopenic – decreased supply
of metabolic fuel to brain
Usually seen at blood sugar < 60mg/dL Usually seen at blood sugar <45 mg/dL
Sympathetic Parasympathetic Due to biochemical injury resulting
from lack of metabolic fuel
Palpitation
Tremor
Pallor
Nervousness
Arousal
Hypothermia
Sweating
Hunger
Lethargy
Weak cry/high pitched cry
Irritabililty
Poor feeding
Seizures
Apnea
Floppiness

20. 20
Cinical clues in the diagnosis of hypoglycemia
Hepatomegaly, vomiting, intractable diarrhea Congenital disorders of glycosylation
Macroglossia, omphalocele,
hemihypertrophy,microcephaly
Beck-with wide man syndrome
(Hyperinsulinism)
Midline defects, poor growth Microphallus,
hepatitis with cholestatic jaundice
Hypopitutarism
Early morning seizures (Fasting), doll facies,
hepatomegaly, Poor growth, acidosis,
hyperuricemia, elevated beta- hydroxy
butyrate and lactate
Glycogen storage diseases (eg: GSD-1)
Hepatomegaly, galactose intolerance and
tubular dysfunction
Fanconi bickel syndrome
Hypotonia, seizures, acrid odour Acyl co-A dehydrogenase deficiency
h/o Fruit juices consumption Hereditary fructose intolerance

21. 21

22. 22
Critical Samples to be sent
 Lab RBS
 S. Insulin/C-peptide
 S. Cortisol/ACTH/17OHP
 GH levels
 TFT
 Blood gas
 Urine for Ketones/Reducing substance
 Blood Ketone
 Blood FFA/βHB
 Ammonia/Lactate
 TMS/GCMS

23. 23

24. Hyperinsulinism
 M/C cause of persistent/refractory hypoglycemia in early infancy
 Onset – early neonatal period to late infancy
 Insulin concentration inappropriately elevated
 Need for higher rates of glucose infusion
 Hypoglycemia occurring without any relation or within 4-8hrs of fasting
 Insulin levels - > 2mU/ml
 Elevated C-peptide
 Insulin:Glucose ratio > 0.3-0.5
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25. Diagnosis of hyperinsulinemia
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Critical criteria Normal Hyperinsulinism
Plasma insulin < 2 uU/ml 2-30+ uU/ml
Plasma β–
hydroxybutyrate
> 2 mmol/L < 2 mmol/L
Plasma free fatty
acids
>1.5 mmol/L < 1.5 mmol/L
Glycemic response to
glucagon
<30 mg/dl >40mg/dl
Critical sample – taken when RBS <50mg/dL

26. Types of Hyperinsulinemia
Transient
Infant of Diabetic mother
SGA babies
Discordant twin
Perinatal asphyxia
Infant of toxemic mother
Persistent
1. Monogenic Forms
KATP hyperinsulinism (Focal/Diffuse)
GDH Hyperinsulinism
SCHAD Hyperinsulinism
GCK Hyperinsulinism
HNF4α Hyperinsulinism
UCP2 Hyperinsulinism
2. Syndromic forms
Beckwith Widemann Syndrome
Usher Syndrome
Costello Syndrome
Perlman Syndrome
Sotos syndrome
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27. 27
Persistent/Refractory Hypoglycemia
Critical Sample –
Hyperinsulinemic
Hypoglycemia
Start Diazoxide
Good response 
Taper off GIR
Transient HHI
Start feeds &
gradually increase the
interval
Poor response
Try to taper Diazoxide

28. Management of persistent/Refractory
Hypoglycemia
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29. Follow up
 Frequent feeding
 Frequent RBS monitoring
 Management of hypoglycemia explained to mother
OFC & neurological monitoring
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30. THANKS

31. Hypoglycemia in older infants and children is analogous to that of adults, in whom glucose homeostasis is maintained by glycogenolysis in the immediate postfeeding period
and by gluconeogenesis several hours after meals. The liver of a 10 kg child contains 20-25 g of glycogen, which is sufficient to meet normal glucose requirements of4-6
mg/kg/min for only 6-12 hr. Beyond this period, hepatic gluconeogenesis must be activated. Both glycogenolysis and gluconeogenesis depend on the metabolic pathway
summarized in Figure 87-1. Defects in glycogenolysis or gluconeogenesis may not be manifested in infants until the frequent feeding at 3-4 hr intervals ceases and infants
sleep through the night, a situation usually present by 3-6 mo of age. The source of gluconeogenic precursors is derived primarily from muscle protein. The muscle bulk of
infants and small children is substantially smaller relative to body mass than that of adults, whereas glucose requirements/unit of body mass are greater in children, so the
ability to compensate for glucose deprivation by gluconeogenesis is more limited in infants and young children, as is the ability to withstand fasting for prolonged periods.
The ability of muscle to generate alanine, the principal gluconeogenic amino acid, may also be limited. Thus, in normal young children, the blood glucose level falls after 24 hr
of fasting, insulin concentrations fall appropriately to levels of <5-10 µU/ mL, lipolysis and ketogenesis are activated, and ketones may appear in the urine. The switch from
glycogen synthesis during and immediately after meals to glycogen breakdown and later gluconeogenesis is governed by hormones, of which insulin is of central
importance. Plasma insulin concentrations increase to peak levels of 5-10–fold greater than their baseline of approximately 5-10 µU/mL after meals, which serve to lower
the blood glucose concentration through the activation of glycogen synthesis, enhancement of peripheral glucose uptake, and inhibition of glucose production. In addition,
lipogenesis is stimulated, whereas lipolysis and ketogenesis are curtailed. During fasting, plasma insulin concentrations fall to ≤5-10 µU/mL, and together with the rise of
counterregulatory hormones, this fall in insulin results in activation of gluconeogenic pathways (see Fig. 87-1). Fasting glucose concentrations are maintained through the
activation of glycogenolysis and gluconeogenesis, inhibition of glycogen synthesis, and activation of lipolysis and ketogenesis. It should be emphasized that a plasma insulin
concentration of >5 µU/mL, in association with a blood glucose concentration of ≤50-55 mg/dL (2.8-3.0 mM), is abnormal, indicating a state of excessive insulin action, here
termed hyperinsulinism, because of failure of the mechanisms that normally result in suppression of insulin secretion during fasting or hypoglycemia. The hypoglycemic
effects of insulin are opposed by the actions of several hormones whose concentration in plasma increases as blood glucose falls. These counterregulatory hormones—
glucagon, growth hormone, cortisol, and epinephrine—act in concert by increasing blood glucose concentrations via activating glycogenolytic enzymes (glucagon,
epinephrine); inducing gluconeogenic enzymes (glucagon, cortisol); inhibiting glucose uptake by muscle (epinephrine, growth hormone, cortisol); mobilizing amino acids
from muscle for gluconeogenesis (cortisol); activating lipolysis and thereby providing glycerol for gluconeogenesis and fatty acids for ketogenesis (epinephrine, cortisol,
growth hormone, glucagon); and inhibiting insulin release and promoting growth hormone and glucagon secretion (epinephrine). Congenital or acquired deficiency of any
one of these hormones is uncommon but will result in hypoglycemia, which occurs when endogenous glucose production cannot be mobilized to meet energy needs in the
postabsorptive state, that is, 8-12 hr after meals or
during fasting. Concurrent deficiency of several hormones (hypopituitarism) may result in hypoglycemia that is more severe or appears earlier during fasting than that seen
with isolated hormone deficiencies. Most of the causes of hypoglycemia in neonates, infants and children reflect inappropriate adaptation to fasting as a result of excess
insulin action, or inadequate counter-regulatory hormone response primarilyof cortisol and growth hormone, or enzymatic defects in the mechanisms for glycogen storage
and release, or defects in gluconeogenesis.
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