pediatric hypoglycemia
TRANSCRIPT
CASE PRESENTATION Dr. Fahad Fayyaz Butt Pediatric Resident 2
CASE: 2y, boy Complaints: Vomiting 2days Loose stools-2days lethargic 1 day
EXAMINATION:General Condition: Lethargic and sick looking, deep rapid breathing, delayed capillary refill >3secs, severely dehydratedVital signs: HR: Tachycardic RR: TachypneicTemp : afebrile Spo2: 99% saturationB.P: Normal B.P.
SYSTEMIC EXAM: CNS: Drowsy and lethargic otherwise unremarkable CVS: S1+S2+No murmurGIT: Soft, No organomegaly, non-tenderChest: Bilateral equal air entry, no adventitious soundsENT: Normal
CBG : Hypocount: 60 mg/dl
pH: 7.03 PCO2: 6.5 HCO3: 1.6 Base Excess: -28 Glu: 60 Lactate: 13.9 Electrolytes: normal
TREATMENT GIVEN IN EMERGENCY : IV 0.9% NaCl Boluses IV D10% Bolus
Provisional Diagnosis: •Gastroenteritis and Severe Dehydration
Past medical history: No prior hospitalization or a severe presentation in ER Birth History: Term , NVD, Admitted in NICU after birth due to hypoglycemia for few hours , Birth Weight: 3.5kg (mother has no reports) Vaccination: Current Nutritional: On regular family diet, high amount of milk intake. Development: Age -appropriate Family history: one of two siblings. Consanguineous No history of miscarriage, still born or developmental delay, significant Metabolic disorder in family
SUMMARY: 2 year old boy Vomiting/loose stool and lethargy for 2 days Severe dehydration with hypoglycemia CBG with Metabolic acidosis No significant past medical/family history. Patient sometime looks sweaty at night and wakes up hungry.
Differential Diagnosis: Gastroenteritis with severe dehydration
Septic Shock Inborn Error of Metabolism
INVESTIGATIONS:Labs: Patient value
CBC
WBC 33.1 x 10^3
ABN:22.9
HGB 9.3 g/dlPLT 587 x 10^3
CRP <5 mg/L
LFTs
Albumin 4.9 g/dLALP 283U/L ALAT 181 U/LT. Bil 0.1 mg/dLTotal Protein 8.3 g/dLPT 12.5 secsAPTT 32.4 secsINR 1.39
Labs: Patient value
Urea and electrolytes
Sodium 135
Potassium 4.1
Chloride 106
HCO3 5
Urea 31
creatinine 0.3
Labs: Patient value
Blood Culture No growth
UrineRoutine WBC: 0-3
RBC: NilCulture No growth
Stool
Routine No Pus CellsNo RBCsNo Ova And Parasites
Culture No Growth
Rota &Adenovirus Negative
Ammonia 43 umol/L , 17-68
INVESTIGATIONS:
COURSE IN THE HOSPITAL: Day 1: •Admitted to ICU•IV NaHCO3 •IV D10% +0.45%NaCl •IV Ceftriaxone•Clinical Status: Markedly Improved
• After 24hours in ICU: • CBG: pH: 7.4, pCO2: 32, HCO3:
20.1• Lac:2.7 Glu: 85mg/dl
Day 2 & 3 : Shifted to ward Full Oral ,Vitally stable, had no episode of fever Discharged with instructions
Since then Child was admitted in Hospital for a total of five times in one year with Identical picture:
Chief complaints Blood gas picture : Low blood glucose and metabolic acidosis Course in hospital
2ND EPISODE: Complaints: runny nose and cough ,fever and vomiting. hypocount: 35mg/dl in ER CBG showed severe Metabolic Acidosis Critical Sample was taken
Indications for critical Sample : 1.Recurrent hypoglycemia 2.Not explained by history and
physical examination
HOW TO COLLECT THE SAMPLE:
1. gray-top tube :Glucose, lactate,
2. red tiger-top tube : Insulin, GH, cortisol,
3. Filter Paper: Acylcarnitine profile
4. dark green-top tube : FFA,
5. lavender-top tube : C-peptide from 2 mL in a lavender-top tube (0.5 mL minimum).
6. Send next voided urine for quantitative determination of organic acids, reducing substances and ketones
CRITICAL SAMPLE IN LH Blood
FFAInsulin
C-peptideGrowth Hormone
CortisolLactate
Acylcarnitine on filter paper
Urine
Urinary Ketones
Urinary Organic acids
Urinary Reducing Substances
HYPOGLYCEMIA • Definition• Clinical Features• Pathophysiology• Differential diagnosis• History and PE• LH approach• Management
DEFINITION OF HYPOGLYCEMIA : Laboratory Serum: less than 50mg/dl
Whipple’s triad
Hypoglycemia
Insulin
Hepatic Glucose output
Glucose
Glucagon Epinephrine
LipolysisFFA and glycerol
Ketones
Growth Hormone
Insulin Sensitivit
yGlucose
utilization
Cortisol
Protein Breakdo
wngluconeogenesis
Excessive Utilization of
Glucose:
Hyperinsulinism
Defect in Ketogenesis
Defect in Ketolysis
Fatty acid Oxidation Defects
Under Production of
Glucose:
Glycogen storage disease
Gluconeogenesis defect
Hormonal Defects: Cortisol
or growth hormone
deficiency
HYPERINSULINISM
Insulin
GlucagonGluconeogene
sisGlycogenesisLipogenesis
Hypoglycemia
PathogenesisFFA Low
Insulin HighC-peptide HighGrowth Hormone
High
Cortisol HighLactate NormalAcylCarnitine
Low
Urinary Ketones
Low
Urinary Organic Acids
Absent
CORTISOL DEFICIENCY
Cortisol
Reduced protein
BreakdownGluconeogene
sis
Hypoglycemia
PathogenesisFFA Raised
Insulin Low C-peptide lowGrowth Hormone
High
Cortisol Low Lactate NormalAcylcarnitine
Normal
Urinary Ketones
Raised
Urinary Organic Acids
Absent
GROWTH HORMONE DEFICIENCY
Growth Hormone
Insulin sensitivity Peripheral glucose Uptake
Hypoglycemia
Pathogenesis FFA Raised
Insulin Low C-peptide lowGrowth Hormone
LowCortisol HighLactate NormalAcylcarnitine
Normal
Urinary Ketones
Raised
Urinary Organic Acids
Absent
GLUCONEOGENESIS DEFECTS
1. Glu. 6 Phosphatase2. Fru. 1.6 Diphoshaphatase3. PEP Cabroxykinase
Gluconeogenesis Hypoglycemia
Pathogenesis FFA Raised
Insulin LowC-peptide LowGrowth Hormone
High
Cortisol HighLactate HighAcylcarnitine
Normal
Urinary Ketones
High
Urinary Organic Acids
Absent
LactateAlanine
Glycerol 3 P
GLYCOGENOLYSIS DEFECT
0, Gly. Synthase3, Debranching Enzy.6, Liver Phophorylase Enzy.9, Phosphorylase kinase
Glucose Release Hypoglycemia
PathogenesisFFA Raised
Insulin Low C-peptide lowGrowth Hormone
High
Cortisol HighLactate Normal to
HighAcylcarnitine
NormalUrinary Ketones
high
Urinary Organic Acids
Absent
Ketone production
FATTY ACID OXIDATION DEFECTS
Acyl CoA Dehydrogena
se
Beta oxidation of
FAHypoglyce
mia
Pathogenesis
FFA HighInsulin Low C-peptide lowGrowth Hormone
High
Cortisol HighLactate Normal to
HighTotal carnitines and acylcarnitines
Total AcylcarnitineUrinary
KetonesLow
Urinary Organic Acids
Dicarboxylic acids
Ketone production
KETOGENESIS DEFECTS
HMG CoA Lyase
HMG CoA synthase
Ketone production
Hypoglycemia
Pathogenesis
FFA HighInsulin Low C-peptide lowGrowth Hormone
High
Cortisol HighLactate Normal to
Highacylcarnitines Acylcarnit
ineUrinary Ketones
Low
Urinary Organic Acids
Dicarboxylic acids
KETOLYSIS DEFECTS
SCOT def.Beta
Ketothiolase deficiency
Ketone utilization
Hypoglycemia
PathogenesisFFA HighInsulin Low C-peptide lowGrowth Hormone
High
Cortisol HighLactate Normalacylcarnitines -
Urinary Ketones
High Urinary Organic Acids
-
Excessive Utilization of
Glucose:
Hyperinsulinism
Defect in Ketogenesis
Defect in Ketolysis
Fatty acid Oxidation Defects
Under Production of
Glucose:
Glycogen storage disease
Gluconeogenesis defect
Hormonal Defects: Cortisol
or growth hormone
deficiency
HISTORY:
History Of presenting
Illness
Age: • Neonate to 2 years of life: MC age of Presentation
• Toddlers or older children: Toxin intake
Trigger: • Period Fasting
Specific Foods • Milk products• fruit juices
Past Medical History • Prior ER visit or
Hospitalizations: labelled as seizure disorders or other disorders.
Birth History
• Antenatal Preeclampsia , GDM
• Natal LGA• Postnatal Hypoxic injury
at birth
Family history • Unexplained deaths in family• Affected members in family
Developmental Milestones • Appropriate for age
PHYSICAL EXAM:General Examination:
Dysmorphic features: Mid facial defects
Growth Charts :
Failure to thriveShort statureUnderweightNeonate: Macrosomia
Vital Signs RR: Deep rapid breathing Temperature: Hypothermia or fever
Systemic Examination:
GIT: Hepatomegaly Umbilical hernia or omhpalocele
Skin : HyperpigmentationEye: CataractGenitalia Ambiguous genitalia
APPROACH
Hypoglycemia Urine
KetonesNon-
glucose Reducing substance
s
Galactosemia
H. Fructose IntoleranceTyrosinemi
a
Approach Continued…
Ketones
Positive
Negative
Hyperinsulinemia
+ Low FFA + High Insulin And C-peptide
FA Oxidation Defects
+High FFA+Undetectable Insulin & C-Peptide
Approach Continued…
Ketones Positive
Serum Lactate
High
Normal
1. Growth Hormone2. Adrenal Insufficiency3. Idiopathic Ketotic Hypoglycemia
Approach Continued…
High Serum Lactate
HepatomegalyGlycogen storage
disease GSD1Gluconeogenesis
defects
No HepatomegalyOrganic
AcidopathyKetolysis Defect
Approach Continued…
TREATMENT
Glucose <50mg/dl
Conscious
Oral trial
Recheck
Drowsy
IV access
IV D10%
Commence IV infusion
<50mg/dl: adjust
infusion
>50mg/dl: Introduce oral
feeds
No IV access
IM Glucagon
Target: 60-140mg/dl
HYPOGLYCEMIA • Definition• Clinical Features• Pathophysiology• Differential diagnosis• History and PE• Critical sample • LH approach• Management
CRITICAL SAMPLE OF THE PATIENT
Blood Patient values Normal rangeFFA - -
Insulin 3.2 4.0-16C-peptide 1.8 1.8-4.7Growth
Hormone 5.2 0-3
Cortisol 1681 69-328Lactate 11.4 0.5-2.2
Acylcarnitine on filter paper
Increased Level of all Acylcarnitine
CRITICAL SAMPLE IN LH Urine Patient Values
Urinary Ketones 3+
Urinary Organic acids Lactic Acids
Urinary Reducing Substances
+Glucose (taken after glucose infusion)
Urinary Amino Acids All in normal range except borderline increased levels
of Alanine, Valine , Phenylalanine and Leucine
OTHER TESTS Tests Values Normal RangeTSH 1.37 0.80-6.26T3 4.7 3.96-8.14T4 13.8 10.45-22.35
CPK levels 123 0-228Total and Free
Carnitines70.439.4
35.0-84.024.0-63.0
2 year old boy
Vomiting/loose stool and lethargy for 2 daysAdmitted 5 times with Severe dehydration & hypoglycemiaNo significant past medical/family history.Patient sometime looks sweaty at night and wakes up hungry.
Labs:
1. CBG: Metabolic acidosis with hypoglycemia2. Critical Sample: Lactic acidosis , rest of profile normal3. Urinary tests done: Ketone 3+4. Other tests: CPK: Normal , TFTs: Normal
Case : Ketotic Hypoglycemia for evaluation
Glucose
Acidosis Lactic acid Ketones Hepatomegaly
Others tests
Patient Low Present Present Present Absent Normal, mild deranged LFTs
Hyperinsulinism
Low Absent Absent Absent Absent Insulin and C-peptide
FA Oxidation defects
Low Absent Absent Absent Present Acylcarnitine profileElevated dicarboxylic acids
Hormone deficiency
Low Present Absent Present Absent Hormone levelsP.E.
Gluconeogenesis
Low Present Present Present Present HyperuricemiaHyperlipidemia
Glycogen storage Disease
Low Present +/- Present Present Present Deranged LFTs
Ketogenesis defects
Low Present Absent Absent Present Elevated acetoacetate levels
Ketolysis Defects
Low Present +/- Present Present Absent Elevated dicarboxylic acids
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