pediatric hypoglycemia

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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