HYPOGLYCEMIA
Hypoglycemia beyond first 72 hours of life is defined as :
• Blood glucose levels lt; 45 mg/dl*
• Symptoms compatible with hypoglycemia, and
• Resolution of symptoms after glucose therapy.
*However, some children may be symptomatic even at blood glucose levels between 45-55 mg/dl.
Present chapter mainly deals with post-neonatal hypo glycemia, while neonatal hypoglycemia is discussed elsewhere (Ch 12.18).
Etiology: Maintenance of normoglycemia depends on: (a) adequate substrate (glucose) supply, (b) appropriate hormonal control, and (c) appropriate metabolic pathways. Insulin is the hypoglycemic hormone while counter-regulatory hormones, e.g. GH, cortisol, glucagon and epinephrine, increase BG levels via various metabolic pathways.
Hypoglycemia may develop due to:
• Substrate deficiency, e.g. prolonged fasting or inadequate energy stores, e.g. low birth weight or severe malnutrition.
TABLE 22.20: Causes of hypoglycemia beyond neonatal period
Persistent/recurrent hypoglycemia
• Substrate deficiency
- Ketotic hypoglycemia
• Hyperinsulinemic states
- Congenital hyperinsulinism
- Familial or sporadic (Nesidioblastosis)
- #946;-cell adenoma in older children
- Beckwith-Wiedemann syndrome
• Deficiency of counter-regulatory hormones
- Growth hormone deficiency
- Cortisol deficiency/Addison disease
- Glucagon deficiency
• Metabolic defects
- Glycogen storage disorders
- Fructose 1, 6 diphosphate deficiency
- Galactosemia
- Fatty acid oxidation defects
- Branched chain ketonuria e.g. MSUD
• Transient hypoglycemia
- Severe malnutrition
- Poisoning e.g. salicylates, alcohol, quinine
- Liver disease e.g. Reye syndrome
- Septicemia
- Iatrogenic: Insulin therapy
• Pseudohypoglycemia in polycythemia
MSUD: Maple syrup urine disease
• Hormonal imbalance, e.g.
hyperinsulinemic states or deficiency of counter-regulatory hormones• Metabolic disorders involving glycogenolysis or neoglucogenesis.
Hypoglycemia in newborns is usually transient and indicates substrate deficiency due to delayed feeding or poor energy stores, while post-neonatal hypoglycemia is usually endocrinal or metabolic in origin and tends to be recurrent or persistent (Table 22.20).
Clinical manifestations of hypoglycemia result from both-direct depression of CNS due to glucopenia and compensatory hypersecretion of epinephrine-principle counter-regulatory hormone, as follows:
• Signs of cerebral glucopenia: headache, confusion, altered sensorium or coma, seizures and ataxia.
• Signs of epinephrine excess: tachycardia, excessive perspiration, pallor, weakness, anxiety, vomiting. Clinical features of hypoglycemia in infancy are
relatively non-specific and include jitteriness, feeding difficulties, hypotonia, hypothermia and pallor.
Diagnosis of hypoglycemia per se is based on BG levels during the attack, while etiological diagnosis in unexplained, persistent or recurrent hypoglycemia requires detailed investigations for endocrinal/metabolic causes. Important investigations in these cases include:
• Serum insulin levels to exclude hyperinsulinemic states
• Growth hormone and cortisol levels for counter- regulatory hormonal defects,
• Serum lactate, free fatty acids and Ketones (#946;-hydroxy- butyrate) levels for metabolic defects, and
• Urine examination for ketones.
All samples must be collected before the treatment for valid results.
Treatment: Acute hypoglycemia is an emergency and irrespective of the cause, the treatment is same - IV Dextrose 10% 2 ml/kg as bolus, followed by continuous infusion at the rate of 6-12 mg/kg/min adjusted with frequent blood glucose monitoring.
Refractory hypoglycemia to above treatment may be treated with IV hydrocortisone (5 mg/kg/d q8hr) or PO Diazoxide or SC Octreotide. Further treatment depends on the identified cause.
Some important causes of persistent/recurrent hypoglycemia in children are as follows:
Ketotic hypoglycemia is the commonest cause of new- onset recurrent hypoglycemia beyond infancy, usually seen in 2-5 year age-group. Exact cause is unknown, probably relates to defective mobilization of alanine from muscles for neoglucogenesis.
Clinically, these cases are generally thin built with history of low birth weight and present with recurrent early morning symptomatic hypoglycemia after prolonged fasting or during intercurrent illnesses.
Diagnosis rests on exclusion of other causes for ketotic hypoglycemia. A shorter period of fasting for 12-18 hours may induce hypoglycemia with ketosis/ketonuria in these cases, as compared to gt;36 hours required in normal children.
Management includes treatment of acute episode with dextrose infusion as well as prevention of recurrence by avoidance of fasting, frequent high-protein, high- carbohydrate meals and treatment of intercurrent illnesses. Most cases resolve spontaneously by 8-9 years of age.
Bedtime administration of corn starch helps to prevent early morning hypoglycaemia, particularly during illnesses.
Hyperinsulinemic states denote failure of the suppression of insulin secretion despite hypoglycemia.
• Transient hyperinsulinemia is common in neonates of diabetic mother due to fetal islet cell hyperplasia in response to high maternal blood glucose, which recovers spontaneously.
• Persistent hyperinsulinemia may be due to: (a) familial/sporadic congenital hyperinsulinism (nesidioblastosis) since infancy, (b) islet cell adenoma in older children, and (c) Beckwith-Wiedemann syndrome.
Neonates and infants with CHI are more prone to brain injury as hyperinsulinism not only causes hypoglycemic damage but also suppresses production of ketones - the alternative fuel to the brain.
Clinically, hyperinsulinemic babies tend to have larger body size with voracious appetite and recurrent episodes of severe hypoglycemia within 1-3 hours of feeding.
Diagnosis may be confirmed by serum insulin levels (gt;5-10 #956;U#8725;ml) during an episode of hypoglycemia, along with characteristic absence of ketosis or ketonuria (d/d counter-regulatory hormonal defects).
Treatment, after acute hypoglycemic control with dextrose infusions, includes PO Diazoxide (10-25 mg#8725; kg/d q6hr) or SC Octreotide (5 #956;g#8725;kg#8725;dose q6hr) to suppress insulin secretion. However, most cases of nesidioblastosis or islet cell adenoma need surgery with subtotal pancreatectomy or tumor removal respectively.
Deficiency of counter-regulatory hormones, e.g. GH or cortisol deficiency, present with signs of primary disease as well as ketosis/ketonuria (d/d hyperinsulinemia) during hypoglycemic episodes and elevated free fatty acids.
Metabolic disorders with hypoglycemia include disorders of glycogenolysis (GSD type Ia) or neoglucogenesis (rare fructose 1-6 diphosphatase deficiency), fatty acid oxidation defects (medium chain fatty acid aceyl-CoA dehydrogenase deficiency) and others, e.g. galactosemia. Hypoglycemia in all of them is associated with ketosis/ketonuria, except fatty acid oxidation defects.
Reactive hypoglycemia denotes hypoglycemia after 2-3 hours of meals, specially seen in children who later develop IDDM or after gastric surgery (dumping syndrome) due to rapid gastric emptying leading to rapid rise in BG levels and consequent increase in insulin secretion.
BIBLIOGRAPHY
1. Vyas V et al. Growth hormone deficiency in children: From suspecting to diagnosing. Indian Pediatr. 2017;54:955.
2. Ayyavoo A et al. Hypothyroidism standard treatment guidelines. Indian Academy of Pediatrics. 2022.
3. Desai MP et al. Newborn screening guidelines for congenital hypothyroidism in India: Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology-Part I: Screening and confirmation of diagnosis. Indian J Pediatr. 2018;85(6):440.
4. Sudhanshu S et al. Newborn screening guidelines for congenital hypothyroidism in India: Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology— Part II: Imaging, treatment and follow-up.
Indian J Pediatr. 2018;85(6):448.5. Indian Academy of Pediatrics: Hyperthyroidism. Standard Treatment Guidelines. 2022.
6. Rose SR et al. Section on endocrinology executive committee; Council on genetics executive committee. Congenital hypothyroidism: Screening and Management. Pediatrics. 2023;151:e2022060419.
7. Dabas A et al. Management of infants with congenital adrenal hyperplasia. Indian Pediatr. 2020;57:159.
8. Vais P et al. Newborn screening and diagnosis of infants with congenital adrenal hyperplasia. Indian Pediatr. 2020;57:49.
9. Indian Academy of Pediatrics: Puberty (Delay/Precocious). Standard Treatment Guidelines. 2022.
10. Bhattacharyya S et al. Diabetes mellitus standard treatment guidelines. Indian Academy of Pediatrics. 2022.
11. Indian Academy of Pediatrics (2021), guidelines for parents: care of a child with diabetes mellitus. [online] Available from: https: / / iapindia.org/pdf/guidlines-for-Care-of-a-child-with- Diabetes-Mellitus. pdf [Last accessed February, 2023].
12. Mayer-Davis EJ et al. ISPAD clinical practice consensus guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2018;19(S27):7.