Glucose levels are maintained after a meal by release from glycogen stores in liver (glycogenolysis), driven by Glucagon. When glycogen stores are low, then glucose can be produced from fat stores by fatty acid oxidation (via ketones) and from protein by gluconeogenesis. The switching over is moderated by cortisol, and growth hormone (reduces insulin resistance) also important. Insulin is the only hormone that lowers blood sugar levels.
Cortisol increases gluconeogenesis, adrenaline increases lipolysis. Hypoglycaemia makes you grumpy, sweaty, pale. You can feel sick with it, and it can give you palpitations. It can cause a wide range of acute, transient neurological symptoms including tremor, confusion, ataxia, weakness, visual disturbance. If severe, it causes seizures, which causes release of glucose from muscles. Some cases of sudden unexpected death are thought to be due to inborn errors of metabolism causing hypoglycaemia.
Recurrent severe episodes in infancy can lead to permanent neurodisability.
There is debate about what level of blood sugar is abnormal, or whether it is only symptomatic low blood sugar that is important. What the level in the blood is, is not the same as levels in the brain, of course. Less than 2.6mmol/l is uncontroversial (note that near patient tests are not very accurate at low levels, which they are not really designed for, so lab confirmation is always required). Generally <3.3 used in practice, but clinical signs important.
Usual cause is acute viral illness with reduced oral intake and vomiting. But this can also be a trigger that reveals an underlying metabolic disorder…
- Neonate? If big liver, remember Galactosaemia and Fructosaemia (reducing sugars in urine). Else Beckwith Wiedemann Syndrome.
- High glucose requirement (see below)? =Hyperinsulinism
- High ammonia? If encephalopathic, metabolic. Else Hyperammonaemia hyperinsulinaemia – second most common congenital cause of hyperinsulinism. Gain of function mutations in the mitochondrial enzyme glutamate dehydrogenase (GDH). Can treat with diazoxide.
- Signs of adrenal insufficiency? Abdominal/back pain, low Na, high K/Ca! Hyperpigmentation.
- Signs of hypopituitarism? Growth failure, midline defects, micropenis.
- Encephalopathy (esp vomiting)? Consider organic aciduria
- Odour? Consider Maple syrup urine disease etc
- Ketones should be present. If not then Fatty acid oxidation disorder eg MCAD.
- Hepatomegaly? Glycogen storage disorders, also galactosaemia, acute liver failure eg Reyes syndrome (this may also be the mechanism in respiratory chain disorders).
- With sepsis and shock consider galactosaemia – usually big liver too
- Overdose? Propranolol, alcohol, salicylates in particular.
- Consanguinity?
- Time of last meal? Endocrine problems can cause symptoms at any time, as can hyperinsulinism. Glycogen storage/synthase problems cause early hypoglycaemia (ie within 3-8 hours).
Investigations
Get 1 ml lactate & 6 ml lithium heparin, bloodspots on neonatal screening card during hypo, and first urine (freeze).
Glucose requirement (mg/kg/minute) can be calculated from the following formula:
- from IV fluids = Infusion rate (ml/hr) x % of glucose infusion x 0.1677/weight.
- from oral feed: glucose content of standard infant formula is 7.2g/ 100ml, and of LBW formula is 8.6g/ 100ml.
Normal is 4-6 mg/kg/min, over 8 is suspicious of hyperinsulinism.
- Insulin and C-peptide. Insulin should be undetectable, C-peptide 0.3-1.12 if hypoglycaemic with appropriate insulin response. Else hyperinsulinism (exogenous, or congenital)
- Blood Glucose – below 2.6 considered true hypoglycaemia. Note that BM sticks are not really designed for low sugars, and are not reliable.
- Lactate – should be normal, otherwise high (with ketones) suggests glycogen storage disorder (with notable exception of Glycogen synthase defect)
- TFTs – hypopituitarism
- Cortisol – hypoadrenalism (cortisol should be high as part of stress response – else consider hypoadrenalism (Addison’s). Infants under 6 months should go over 800, older should be over 500. If low cortisol but GH >15 unlikely to be pituitary problem.
- LFTs – beware primary liver problem
- U&Es, Calcium – Low sodium, high potassium/Ca seen in hypoadrenalism
- Ammonia – for organic acidaemias etc, or primary liver problem
- Amino acids – for Maple Syrup Urine Disease etc
- Carnitine, hydroxybutyrate – for Fatty Acid Oxidation (FAO) disorders
- Acylcarnitines (blood spot) – for FAO disorders
- Free Fatty acids – for FAO disorders, esp FFA/3OH-butyrate ratio (ketones are made from FFA so should be higher or not much lower, else block)
- Blood gas – ?Acidosis
- Urine for reducing sugars (Galactosaemia etc),
- Urine/blood for organic acids
Prognosis
Mostly ketotic hypoglycaemia, due to starvation/vomiting. Adequate history? Beware encephalopathy, raised ammonia, hepatomegaly.
75 LGA newborns with hypoglycaemia followed up to age 4 – no late effects. [Archives of Disease in Childhood 2005;90]