Overview

Definition:
-Hypoglycemia is a condition characterized by abnormally low blood glucose levels, typically below 70 mg/dL (3.9 mmol/L) in infants and children
-Persistent or severe hypoglycemia can lead to neurological damage due to the brain's reliance on glucose for energy.
Epidemiology:
-Hypoglycemia is common in neonates (up to 50% in high-risk infants), and less frequent in older children
-The incidence varies based on risk factors
-Inborn errors of metabolism and hormonal deficiencies are key causes of recurrent hypoglycemia.
Clinical Significance:
-Timely and accurate evaluation of pediatric hypoglycemia is crucial to identify underlying causes, prevent irreversible neurological sequelae, and guide appropriate management
-Failure to diagnose can result in developmental delays, seizures, coma, and death
-DNB and NEET SS examinations frequently test this topic.

Clinical Presentation

Symptoms:
-Neonatal hypoglycemia: Jitteriness
-Lethargy
-Poor feeding
-Irritability
-Tachypnea
-Hypotonia
-Cyanosis
-Seizures
-Older children: Shakiness
-Sweating
-Palpitations
-Tremors
-Hunger
-Confusion
-Drowsiness
-Weakness
-Blurred vision
-Headaches
-Behavioral changes
-Seizures
-Coma.
Signs:
-Pallor
-Diaphoresis (sweating)
-Tachycardia
-Hypotonia
-Irritability or lethargy
-Poor feeding
-Failure to thrive
-In recurrent cases: Microcephaly
-Developmental delay
-Hepatomegaly or splenomegaly (depending on cause).
Diagnostic Criteria:
-Whipple's triad: 1
-Symptoms consistent with hypoglycemia
-2
-Low plasma glucose level concurrent with symptoms
-3
-Relief of symptoms upon administration of glucose
-Laboratory confirmation of low glucose with presence of signs and symptoms is essential.

Diagnostic Approach

History Taking:
-Detailed birth history (gestational age, maternal diabetes)
-Feeding history (type, frequency, volume)
-Age at onset of symptoms
-Frequency and severity of hypoglycemic episodes
-Family history of metabolic disorders or sudden infant death
-Medications or unusual food intake
-Previous hospitalizations.
Physical Examination:
-General appearance (well-nourished, dysmorphic features, signs of dehydration)
-Vital signs
-Neurological examination (alertness, tone, reflexes)
-Abdominal examination (hepatomegaly, organomegaly)
-Skin examination (nevus sebaceous of Jadassohn syndrome).
Investigations:
-Initial: Blood glucose (finger prick, followed by venous glucose)
-Plasma glucose, insulin, C-peptide, cortisol, growth hormone, IGF-1, IGFBP-3, free fatty acids, ketones, lactate, ammonia, acylcarnitine profile, urine organic acids
-In suspected specific syndromes: Genetic testing
-Imaging: Liver ultrasound (for hepatomegaly), brain MRI (if seizures or neurological deficits)
-For persistent unexplained hypoglycemia: Ketogenic amino acid analysis and urine/serum for organic acids.
Differential Diagnosis:
-Hyperinsulinism (congenital hyperinsulinism, nesidioblastosis, post-Bariatric surgery, drug-induced)
-Hormonal deficiencies (cortisol deficiency, growth hormone deficiency, glucagon deficiency, epinephrine deficiency)
-Ketotic hypoglycemia
-Non-ketotic hypoglycemia
-Inborn errors of metabolism (galactosemia, glycogen storage diseases, fatty acid oxidation defects, fructose-1,6-bisphosphatase deficiency)
-Sepsis
-Hypothermia
-Macrosomia
-Small for gestational age infants
-Pancreatic tumors (rare)
-Liver disease.

Evaluation Of Hyperinsulinism Vs Hormonal Deficiencies

Hyperinsulinism Evaluation:
-During a hypoglycemic episode, measure plasma glucose, insulin, and C-peptide
-High insulin levels with suppressed C-peptide in the presence of hypoglycemia strongly suggest inappropriate insulin secretion
-Look for elevated proinsulin
-Oral glucose tolerance test can be provocative in ambiguous cases
-Genetic testing for CHI genes (KCNJ11, ABCC8, GCK, HNF4A, etc.) is key.
Hormonal Deficiency Evaluation:
-Evaluate for cortisol deficiency (low serum cortisol, low ACTH, low response to ACTH stimulation test)
-Assess growth hormone deficiency (low GH, low IGF-1, low IGFBP-3)
-Measure glucagon (low in glucagon deficiency)
-Evaluate for epinephrine deficiency (less common, assessed by catecholamine levels during stress/hypoglycemia)
-Consider thyroid function tests if hypothyroidism is suspected.
Distinguishing Features:
-Hyperinsulinism typically presents with high insulin levels, low ketones, and sometimes elevated C-peptide, while hormonal deficiencies often show low counter-regulatory hormones (cortisol, GH, epinephrine, glucagon) and preserved insulin secretion
-Presence of ketonuria supports utilization of fat reserves, often seen in conditions other than hyperinsulinism.
Etiology Of Hormonal Deficiency: Hormonal deficiencies can be congenital (e.g., panhypopituitarism, congenital adrenal hyperplasia leading to cortisol deficiency) or acquired (e.g., pituitary tumors, hypothalamic lesions, sepsis affecting hormone production).

Management

Initial Management:
-Prompt intravenous glucose administration is critical
-For neonates: 10% dextrose infusion at 6-8 mg/kg/min
-For older children: 10-25% dextrose
-Continuous glucose monitoring is essential
-Identify and treat precipitating factors (e.g., infection, poor feeding).
Medical Management:
-For hyperinsulinism: Frequent small feeds, uncooked cornstarch (to provide sustained glucose release), diazoxide (inhibits insulin release), octreotide (somatostatin analogue, reduces insulin secretion)
-Glucagon therapy for persistent severe hypoglycemia
-For hormonal deficiencies: Hormone replacement therapy (hydrocortisone for cortisol deficiency, recombinant GH for GH deficiency, glucagon therapy for glucagon deficiency).
Surgical Management: Subtotal or near-total pancreatectomy may be considered for severe, medically refractory congenital hyperinsulinism unresponsive to diazoxide and octreotide.
Supportive Care:
-Close monitoring of blood glucose levels, vital signs, and neurological status
-Nutritional support with adequate caloric intake
-Education of parents/caregivers on recognition and management of hypoglycemia
-Regular follow-up with pediatric endocrinology.

Complications

Early Complications:
-Seizures
-Neurological damage (cerebral edema, brain injury)
-Coma
-Cardiac dysfunction
-Death
-Lactic acidosis.
Late Complications:
-Developmental delay
-Intellectual disability
-Seizure disorders
-Learning disabilities
-Behavioral problems
-Growth retardation.
Prevention Strategies:
-Early recognition of symptoms
-Prompt and adequate glucose administration
-Identification and treatment of underlying etiology
-Consistent monitoring and follow-up
-Parental education.

Key Points

Exam Focus:
-Differentiate between hyperinsulinemic and hormonal causes of hypoglycemia based on lab values (insulin, C-peptide, cortisol, GH)
-Understand Whipple's triad
-Recognize the importance of prompt glucose administration
-Recall management strategies for specific etiologies.
Clinical Pearls:
-Always obtain glucose, insulin, and C-peptide simultaneously during a symptomatic hypoglycemic episode
-Consider ketotic vs non-ketotic hypoglycemia
-In neonates, always rule out sepsis and inborn errors of metabolism
-Cornstarch is a lifesaver for chronic ketotic hypoglycemia.
Common Mistakes:
-Delaying glucose administration
-Inadequate volume or concentration of dextrose
-Failure to investigate underlying etiology for recurrent hypoglycemia
-Misinterpreting lab values (e.g., confusing insulin level with insulin resistance)
-Not considering rare causes like pancreatic tumors.