EM guidemap - Hypoglycemia

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Introduction

Clinical presentation

Medical decision-making

Appendix
Introduction

Hypoglycemia is defined as a blood sugar < 50 mg/dl

- although the absolute figure used in the medical literature varies from 40 - 50mg/dl, the precise figure is not important from an emergency physician's perspective, because any patient with a blood sugar < 50 mg/dl should be presumed to have hypoglycemia until proved otherwise

(* the whole blood glucose is 10 - 15% less than the serum/plasma glucose; most pediatric experts agree that children are hypoglycemic if the blood sugar < 40 mg/dl)

- the clinical definition of hypoglycemia also implies that the patient has symptoms consistent with hypoglycemia and that the symptoms resolve within minutes following the effective treatment of the hypoglycemia (Whipple's triad)

(* some patients with long-standing diabetes may develop hypoglycemic symptoms at a higher threshold of 50 - 75 mg/dl; or by contrast, only at a lower threshold of 30 - 50mg/dl due to a state of hypoglycemic unawareness; young healthy adult females may develop an asymptomatic blood sugar level of 40 mg/dl during a prolonged fast; children with type 1 glycogen storage disease may remain asymptomatic despite long-standing hypoglycemia < 50 mg/dl)

- there are many classification systems of hypoglycemia (see appendix) that are of little use to an emergency physician, who may find it more useful to divide hypoglycemic patients into 4 broad groups:-

1) Hypoglycemia that develops in diabetic patients, who are taking insulin and/or oral hypoglycemic agents

- this is the most common group of hypoglycemic patients seen in the ED

- common causes of hypoglycemia in IDDM include:-

- although these factors play an important role in causing hypoglycemia, many diabetic patients develop hypoglycemia due to factors beyond their personal control

- various factors may affect a diabetic patient's awareness of the symptoms of hypoglycemia

- patients with long-standing type 1 diabetes develop a loss of the secretory response of glucagon in response to hypoglycemia and a lower threshold for the release of epinephrine (epinephrine is released but at lower glucose levels) => such patients have a syndrome of defective glucose counter-regulation that renders them more likely to develop hypoglycemia

- type 1 diabetic patients, who have tightly controlled diabetes, may also develop a state of hypoglycemic unawareness, which predisposes them to recurrent hypoglycemic episodes

- hypoglycemic unawareness is a state characterized by the loss of warning symptoms of hypoglycemia that previously prompted the diabetic patient to eat => it is often too late for the diabetic patient with hypoglycemic unawareness to abort the episode of impending hypoglemia by self-treatment => the risk of severe iatrogenic hypoglycemia is increased > 6x

- lower glucose concentrations are also required to elicit autonomic and symptomatic responses to hypoglycemia in patients with IDDM during intensive therapy with insulin

- the combination of the i) syndrome of defective glucose counter-regulation + ii) state of hypoglycemic unawareness + iii) elevated glycemic thresolds during intensive treatment with insulin can be conceptualized as a state of hypoglycemia-associated autonomic failure in IDDM, that results in a perpetuating cycle of recurrent hypoglycemia

- it is important to realize that scrupulous avoidance of iatrogenic hypoglycemia for a few weeks can reverse the state of hypoglycemic unawarenesss and partially restore the critical epinephrine response to hypoglycemia

2) Post-absorptive hypoglycemia in a non-diabetic patient, that appears spontaneously in the fasting state (> 4 - 12 hours after the last meal)

- this group of patients can be subdivided into two groups - ill-appearing patients and healthy-appearing patients

Ill-appearing patients may have sepsis, chronic liver or renal failure, an endocrinopathy resulting in deficiencies of cortisol or thyroid hormone, acute-on-chronic alcohol abuse superimposed on chronic liver disease +/- a state of chronic malnutrition and inanition

- it is unknown what causes hypoglycemia in septic patients

- hypoglycemia is only common in acute liver failure when the liver damage is massive and rapid, and significant hypoglycemia is rare in chronic liver disease and hepatitits

- hypoglycemia is uncommon in cortisol and growth hormone deficiency in adults, but may produce symptomatic hypoglycemia, especially after a long fast, in neonates and children < 5 years

- hypoglycemia is not common in the epinephric-deficient state, that follows a bilateral adrenalectomy, if cortisol replacement is adequate

- alcohol-induced hypoglycemia in the non-diabetic patient typically follows binge drinking, by 6 - 24 hours, if the chronic alcoholic patient also doesn't eat food, and also has depleted hepatic glycogen stores due to malnutrition

(* alcohol-induced hypoglycemia is suggested by the presence of documented hypoinsulinemic hypoglycemia, low C peptide and pro-insulin levels, elevated serum alcohol, mild metabolic acidosis and increased serum beta-hydroxybutyrate)

Healthy-appearing patients with recurrent episodes of spontaneous post-absorptive hypoglycemia usually have an abnormal state of hyperinsulinism

- the primary feature of hyperinsulinism are recurrent episodes of symptomatic hypoglycemia, which may also occur postprandially if severe, but milder cases may only present after a prolonged fast of 12 - 24 hours

- the most common causes of hyperinsulinism include insulinoma, covert insulin or sulfonylurea drug use and rarely insulin autoantibodies or tumors producing insulin-like substances

- the majority of non-beta cell tumors causing hypoglycemia are mesenchymal in origin (fibrosarcoma, mesothelioma, leiomyosarcoma, liposarcoma, hemangiopericytoma, neurofibroma and lymphosarcoma) and they are large in size, slow growing even if malignant, and often retro-peritoneal in location; hypoglycemia is rarely associated with adrenocortical tumors, carcinoid tumors, hepatomas and various hematological malignanacies

(* see the appendix for a list of causes of spontaneous post-absorptive hypoglycemia)

3) Post-prandial hypoglycemia

- patients who develop autonomic symptoms 2 - 3 hours postprandially are regarded as having reactive hypoglycemia, which is of two major types i) alimentary hypoglycemia and ii) functional hypoglycemia

- alimentary hypoglycemia is seen in some patients following upper gastro-intestinal surgery - gastrectomy, gastroenterostomy, vagotomy and pyloroplasty - and it is characterized by symptoms of hypoglycemia 2 hours postprandially + concurrent hypoglycemia confirmed on blood glucose testing

- although many patients with those types of surgery have a blood glucose nadir of < 50 mg/dl on oral glucose load testing, most of those patients do not have symptoms of hypoglycemia; also, many of those patients may not manifest hypoglycemia after a mixed meal => patients with a history of postprandial autonomic symptoms should therefore have a blood glucose checked after a spontaneous postprandial meal, and they should not undergo formal oral glucose load testing

(* also, 10% of normal people have a plasma glucose nadir < 50 mg/dl two hours after an oral glucose load)

- patients with functional hypoglycemia have postprandial autonomic symptoms without hypoglycemia + a normal oral glucose load test; the etiology is thought to be functional and not organic in origin

- children with galactosemia or hereditary fructose intolerance may develop postprandial hypoglycemia if exposed to diets containing lactose and fructose respectively

4) Pediatric hypoglycemia

- transient neonatal hypoglycemia is very common, and may not require admission or intensive investigation

- however, hypoglycemia in a neonate (or infant) that is recurrent or persistent  may signify more serious pathology

(* see the medical decision-making section for a basic approach to diagnosing the cause of hypoglycemia in infants and children)
 
Clinical presentation

- the symptoms of hypoglycemia can be divided into two basic groups - hyperadrenergic symptoms and neuroglycopenic symptoms
 

 Hyperadrenergic symptoms
  • anxiety
  • nervousness
  • tremulousness
  • irritability
  • nausea and vomiting
  • palpitations and tachycardia
  • sweating
  • pallor
  • hypersalivation
  • pupillary changes
  Neuroglycopenic symptoms
  • decreased cognitive ability
  • agitation and emotional lability
  • sensations of warmth (despite cool clammy skin)
  • blurred vision
  • slurred speech
  • lethargy
  • confusion
  • unresponsiveness
  • focal neurological deficits
  • psychotic behaviour
  • seizures

- hyperadrenergic symptoms are more common when the blood glucose drops rapidly, and they are due to autonomic nervous system stimulation (both sympathetic and cholinergic)

- it is not possible to define a blood glucose concentration below which neuroglycopenic symptoms invariably occur, and above which neuroglycopenic symptoms never occur, although symptoms usually occur when the blood glucose is less than 50 mg/dl

- poorly controlled diabetics often first experience hypoglycemic symptoms at higher glucose levels (60 - 80 mg/dl); by contrast, well controlled diabetics may only experience hypoglycemic symptoms when the blood glucose is 30 - 50 mg/dl

- patients with long-standing diabetes may develop an autonomic neuropathy, and they may only manifest neuroglycopenic symptoms, and no hyperadrenergic symptoms, in response to hypoglycemia

- symptomatology of hypoglycemia also depend on the patient's age => neonates may develop non-specific signs such as feeding difficulties, irritability, twitching, jitteriness, lethargy, hypotonia, tachypnea, hypothermia and apnea

- severe and prolonged hypoglycemia may cause permanent brain damage (mental retardation), especially in neonates and children => patient may present with mental retardation or behavioural changes from previous episodes of prolonged hypoglycemia
 
Medical decision-making in the ED

Hypoglycemia should be presumed to be present in all patients presenting to the ED with altered mental or psychiatric status, and hypoglycemia should be expeditiously excluded by rapid bedside glucose testing

- blood sampling for laboratory glucose testing should also be routinely performed to confirm the results of rapid glucose testing, but hypoglycemia therapy should never be witheld pending laboratory confirmation of bedside testing results

(* bedside testing strips may be inaccurate at the extremes of the blood sugar range; it is highly recommended that blood sampling be performed prior to the administration of glucose, and that additional tubes of blood be obtained for any necessary additional testing that may be required eg. serum insulin, serum C peptide, serum proinsulin)

Treatment of hypoglycemia in an ED setting

Glucose should immediately be administered to patients with hypoglycemia and altered mental status

- the glucose should preferably be given orally if the patient is awake and can swallow water safely with no risk of aspiration

The dose of oral glucose should be 10 - 20g in an adult patient

- suitable oral forms include 120cc of orange juice (10 - 15g glucose) +/- few teaspoons of added sugar (5g glucose/teaspoon of granulated sugar), glucose tablets (5g glucose/tablet), honey (older children and adults), maple syrup, or 240cc of milk

(* 5g of glucose is adequate for an infant or toddler; eating more than 20 - 30g does not increase the rate of recovery and may produce hyperglycemia in the hours following recovery from hypoglycemia; fruit juices [containing fructose] are an unsuitable form of carbohydrate; baseline glucose requirements depends on the patient's age = 5 - 6 mg/kg/min for premature infants, 3 - 5 mg/kg/min for neonates and infants, and 2 - 3 mg/kg/min for older children and adults)

- the oral glucose dose should be repeated x 3 if needed

- a meal containing complex carbohydrates should follow successful oral glucose therapy to ensure long-lasting effects on the blood glucose

- if the patient's mental status deteriorates during oral therapy, parenteral glucose therapy is indicated

The parenteral dose of glucose for an average adult = 25 - 50g of glucose as a 50% D/W solution

(* 0.25 - 0.5mg/kg of glucose for pediatric patients - diluted to a 25% solution for children (1 - 2ml/kg), and diluted to a 10% solution for infants and neonates (2.5 - 5.0ml/kg), because extravasation of hyperosmolar dextrose solutions can cause local tissue necrosis)

- a maintenance 10% D/W solution at 3 ml/kg/hour should follow the 50% D/W bolus if recurrent hypoglycemia is anticipated (eg. massive insulin or sulfonylurea overdose, sepsis, severe malnutrition, liver failure, known enzyme disorder), or if the patient cannot take oral carbohydrate following recovery from the IV loading dose of glucose => the serum glucose should be maintained above 100mg/dl

(* neonates/infants require higher maintenance doses of 4 - 5ml/kg/hour; large amounts of 10% D/W can produce water intoxication => preferably use 10% D/W pre-mixed in 0.45% N/S or 0.9% N/S if a long-term continuous glucose infusion is required; hyperinsulinemic patients may sometimes require higher maintenance rates of glucose therapy (10 - 25mg/kg/min); avoid serial pulse boluses of glucose in sulfonylurea-induced hypoglycemia, because the temporary hyperglycemia induced by pulse boluses of glucose may promote increased insulin secretion => recurrent hypoglycemia)

- failure to respond to glucose is an indication for glucagon sc, IM or IV

Glucagon dose = 1mg in adults (30 mcg/kg - children, 50 mcg/kg - neonates)

- glucagon takes 10 - 20 minutes to work, and glucagon's action is short-lived (15 - 20 minutes)

(* glucagon only works if the patient has adequate liver glycogen stores; suspect depletion of liver glycogen stores, type 1 glycogen storage disease, or an abnormality in fatty acid oxidation if the blood glucose doesn't increase by 50% within 30 minutes of glucagon administration; glucagon should be diluted in water - and not in the manufacturer-supplied phenol diluent - if administered to children, or if multiple glucagon doses are required in adults; glucagon is theoretically contraindicated in sulfonylurea-induced hypoglycemia because it increases insulin secretion, but it is widely used in clinical practice without any problems)

- empirically administer steroids (hydrocortisone = 1 - 2 mg/kg IV every 6 hours) if the patient remains refractory to standard hypoglycemia therapy, or if adrenal deficiency is suspected

- diazoxide or octreotide (potent inhibitors of insulin release) may be indicated for hyperinsulinemic patients, especially patients with sulfonylurea-induced hypoglycemia

- octreotide is used for sulfonylurea overdoses, in order to decrease the chance of recurrent hypoglycemia; although the optimal dose and frequency of administration has not been worked out, octreotide can be administered subcutaneously at an initial dose of 50 - 125 mcg, and repeated doses (50 - 100 mcg) can be given subcutaneously at 6 - 12 hourly intervals

- diazoxide is given IV at 3 - 5mg/kg for neonates, and 1 - 3 mg/kg for infants, every 8 hours; diazoxide should be slowly over 30 minutes to prevent iatrogenic hypotension

Determining the cause of spontaneous hypoglycemia in non-diabetic adults

- the cause may be readily apparent in ill-appearing adult patients eg. sepsis, renal failure, acute liver failure, CHF, endocrine hormone deficiencies, alcohol abuse in malnourished patients

(* see the appendix for a more comprehensive list of causes of spontaneous hypoglycemia in ill-appearing patients)

- the most common cause of spontaneous hypoglycemia in healthy-appearing adult patients is due to the effect of drugs (eg. ethanol, salicylates) or disorders causing hyperinsulinism

- disorders causing hyperinsulinism include:-

- generally, a number of simultaneous criteria are used to diagnose insulinoma - further in-hospital diagnostic testing for insulinoma may be required; diagnostic tests include a prolonged fasting (72 hours) test and serial glucose/insulin measurements; C-peptide suppression test, plasma beta-hydroxybutyrate level at the end of a prolonged fast, and the serum glucose response to glucagon at the end of a prolonged fast

- hypoglycemia due to insulin antibodies is very rare, but should be suspected in patients with auto-immune diseases or plasma cell dyscrasias, or following exposure to a sulfhydryl-containing medication (methimazole, tiopronin, glutathione, captopril, D-penicillinamine) or procainamide or hydralazine; the insulin level is very high (> 100 muU/ml) and the C-peptide level is incompletely suppressed

- factitious hypoglycemia due to surreptitious insulin use is suggested by high insulin levels but low C-peptide levels

- factitious hypoglycemia due to surreptitious sulfonylurea use should always be excluded prior to diagnosing an insulinoma, by checking the plasma/urine for the presence of sulfonylureas

(* see the appendix for a table differentiating hyperinsulinism due to insulinoma from factitious hyperinsulinsim)

- non-islet cell tumors causing hypoglycemia are often large (> 25g) and clinically apparent; testing for insulin-like peptides (insulin-like growth factor II factor) to detect the presence of occult tumors may sometimes be required

Determining the cause of spontaneous hypoglycemia in infants and children

- transient hypoglycemia is common in neonates, and is suggested by easily correctable hypoglycemia in the newborn

- transient hyperinsulinemic neonatal hypoglycemia is seen in neonates of diabetic or pre-eclamptic mothers, premature infants, small-for-gestational age infants, infants with fetal distress or peri-natal asphyxia or erythroblastosis fetalis, fetal-alcohol syndrome infants, hypothermic infants, infants of mothers taking hypoglycemia-inducing drugs, and infants with congenital heart disease

- hyperinsulinemic infants commonly present with increased appetite and demand for feedings, jitteriness, wilting spells, and seizures; hypoglycemia develops 4 - 8 hours after feedings and high doses of glucose (10 - 15 mg/kg/min) may be required to maintain a blood glucose > 100mg/dl; acidosis and ketosis are usually absent and elevated levels of serum proinsulin and C-peptide are present

- persistent hyperinsulinism in infants can be due to familial and non-familial hyperinsulinism, beta-cell adenoma (insulinoma), beta cell hyperplasia and factitious hyperinsulinism (sulfonylurea use)

- other causes of newborn hypoglycemia include endocrine deficiency and congenital inborn errors of metabolism

Severe, recurrent, or persistent hypoglycemia in neonates or infants should suggest serious pathology and a diagnostic evaluation must be initiated

- many diseases cause hypoglycemia in neonates/infants, and diagnostic elucidation often requires a specialist consultation and further diagnostic testing => an emergency physician should at least obtain sufficient blood sample tubes at the time of ED presentation to allow for further diagnostic testing prn

- blood sampling at the time of presentation of spontaneous hypoglycemia is critical, and "didja" tubes should always be obtained

- "didja" tubes refers to critical blood sampling tubes that should have been taken at the time of ED presentation, so that nobody can later ask whether those "didja" tubes were taken

- critical blood sampling tubes include:-

(* see an algorithm based on the critical blood sample, that may help to determine the cause of post-absorptive hypoglycemia in infants)

- idiopathic ketotic hypoglycemia is the most common cause of hypoglycemia in childhood; other common causes of childhood hypoglycemia include drug-induced hypoglycemia (salicylates, alcohol), large non-pancreatic tumors, fulminant liver disease, and factitious hypoglycemia (insulin and sulfonylurea)

(* see the table of causes of pediatric hypoglycemia based on age)

- clinical clues may sometimes be helpful in suggesting a particular etiology when the cause of pediatric hypoglycemia is not apparent
 

Clinical clue table in pediatric hypoglycemia
Clinical disorder Clinical clues
Hyperinsulinemia - transient  
Small for gestation age and asphyxiated infants
  • self-evident
Infants of diabetic mothers
  • diabetic mother
  • large for gestational age, macrosomic, polycythemic and ruddy, plethoric appearance
  • multiple congenital abnormalities
Erythroblastosis fetalis
  • self-evident
Beckwith-Wiedemann syndrome
  • anterior abdominal wall defects, gigantism, macroglossia, microcephaly, visceromegaly, distinctive lateral earlobe fissures, hemihypertrophy
Some other causes of transient hyperinsulinemic hypoglycemia in newborns - congenital heart disease, hypothermia, infection, premature infant, hypoglycemia-inducing drug use by the mother, maternal pre-eclampsia,  fetal alcohol syndrome, fetal distress of any cause  
Hyperinsulinemia - Persistent  
Genetic defects of beta-cell regulation
  •  rare
  • suspected when there is an absent history of maternal diabetes or macrosomia, and the neonate is also not small-for-dates or premature
  • plasma insulin > 10 muU/ml
Hyperinsulinism/hyperammonia syndrome
  • rare
  • presents later in infancy
Beta-cell adenoma (insulinoma)
  • rare and usually sporadic
  • MEA syndrome not common
Drug-induced (surreptitious use of insulin or OHA)
  • clinical suspicion of Muchausen by proxy (intentional use)
  • parents diabetics (accidental use)
  • exogenous insulin administration suspected if insulin levels are very high and C-peptide levels absent
  • exogenous sulfonylurea causes elevated serum C-peptide and elevated insulin levels
Some other causes  
Non-beta cell tumors
  • tumors usually large and palpable, and usually of mesenchymal origin eg. Wilms tumor, hepatoblastoma
Drug-induced
  • salicylates, alcohol, pentamidine, propanolol, disopyramide, quinine
Fatty acid oxidation defects (long chain acyl CoA dehydrogenase deficiency, medium chain acyl CoA dehydrogenase deficiency)
  • hypoketotic hypoglycemia follows an intercurrent illness or short fast
  • plasma free fatty acids levels are markedly elevated during episodes
  • growth failure and mental retardation
  • hepatomegaly or cardiomyopathy or myopathy in long chain FAO defects
  • may also present with unexplained metabolic acidosis or recurrent myoglobinuria
  • may mimic Reye's syndrome and cause sudden death
Carnitine deficiency
  • cardiomyopathy and progressive heart failure, sudden death
  • progressive proximal muscle weakness, hypotonia
  • recurrent Reye-like episodes
  • recurrent hypoketotic hypoglycemic encephalopathic episodes
Glycogen storage disease (glycogen storage disease type I, glycogen storage disease type 0, GSD types III, VI)
  • type 1A have marked hepatomegaly, eruptive xanthomas and lipaemia retinalis, pancreatitis, delay in growth and development
  • hyperuricemia and nephrocalcinosis 
  • increased serum lipids and lacticacidosis
  • hypoglycemia does not respond to glucagon
Galactosemia
  • postprandial hypoglycemia, provoked by lactose in diet
  • lethargy, hypotonia, jaundice
  • vomiting, diarrhea, E Coli sepsis
  • liver disease
  • cataracts
  • poor growth, learning problems
  • non-glucose reducing substance in urine
Hereditary fructose intolerance
  • asymptomatic until fruit or juices added to diet => postprandial hypoglycemia
  • recurrent vomiting, failure to thrive, hepatomegaly
  • glucosuria, proteinuria, aminoaciduria (Fanconi syndrome)
  • acidosis and tachypnea
Cortisol deficiency
  • neonatal adrenal insufficiency most commonly due to congenital adrenal hyperplasia (ambiguous genitalia, hyponatremia, hyperkalemia, buccal and skin hyperpigmentation)
Growth hormone deficiency
  • neonatal hypopituatrism suggested by microcephalus, microphallus, hepatitis or septo-optic dysplasia
  • short stature and failure of growth in older children
Idiopathic ketotic hypoglycemia

(most common cause of childhood hypoglycemia)
  • between 18 months - 5 years, resolves by 9 years
  • provoked by fast or intercurrent illness limiting food intake
  • ketonuria often precedes hypoglycemia
  • insulin levels are appropriately low, excluding hyperinsulinism
Hepatic or renal failure
  • typical signs of failure
Jamaican vomiting sickness
  • consumption of unripe akee fruit by malnourished infant
Reye's syndrome
  • intractable vomiting, hypernea and altered LOC following recent influenza or varicella infection
Amino acid or organic acid metabolic defect
  • failure to thrive, delay in growth and development, hepatomegaly, recurrent vomiting
  • hyperchloremic acidosis, organic aciduria, hyperammonemia during hypoglycemic episode

Patient disposition to hospital or home

- an emergency physician should consider a number of factors when deciding whether to admit the patient to hospital, or send the patient home

Criteria for hospital admission - diabetic patients, who are taking short-acting insulin preparations, do not necessarily require admission, unless massive amounts of those insulin preparations were administered

- all sulfonylurea drugs can produce recurrent hypoglycemia, and routine admission is warranted whenever sulfonylurea drugs are the suspected/known cause of the hypoglycemia
 
Appendix

 

Causes of hypoglycemia in the non-diabetic patient
 Post-absorptive

 Drugs

  •  insulin
  • sulfonylureas
  • alcohol
  • pentamidine
  • quinine
  • salicylates
  • sulfonamides
 Critical illnesses
  • liver failure
  • renal failure
  • congestive heart failure
  • sepsis
  • inanition
 Hormonal deficiencies
  • cortisol or growth hormone, or both (panhypopituatrism)
  • glucagon
  • adrenaline
 Non-beta cell tumors

 Endogenous hyperinsulinism

  • pancreatic insulinoma
  • pancreatic beta cell disorder
  • beta cell secretagogues (eg. sulfonylureas)
 Autoimmune hypoglycemia
  • insulin antibodies
  • insulin receptor antibodies
 Hypoglycemias of infancy and childhood

 Postprandial (reactive) hypoglycemia

 Congenital deficiencies of enzymes of carbohydrate metabolism

  • hereditary fructose intolerance
  • galactosemia
 Alimentary hypoglycemia

 
Classification of hypoglycemia based on the appearance of the patient
 Patient appears healthy

 No coexistent disease

 Drugs

  • ethanol
  • salicylates
  • quinine
  • haloperidol
 Insulinoma

 Islet cell hyperplasia

 Non-insulinoma pancreatogenous hyperinsulinism

 Persistent hyperinsulinemic hypoglycemia of infancy

 Factitious hypoglycemia from insulin or sulfonylurea

 Severe exercise

 Ketotic hypoglycemia of childhood

 Compensated coexistent disease

 Drugs

  • dispensing error
  • disopyramide
  • beta blocker
  • sulfhydryl or thiol drugs with autoimmune insulin syndrome
  • unripe akee fruit containing hypoglycan (+ malnutrition)
 Patient appears ill

 Drugs

  • pentamidine and pneumocystis pneumonia
  • sulfamethoxazole and trimethoprim and renal failure
  • propoxyphene and renal failure
  • quinine and cerebral malaria
  • topical salicylates and renal failure
 Predisposing illness
  • small for gestational age
  • Beckwith-Wiedemann syndrome
  • erythroblastosis fetalis
  • infant of diabetic mother
  • glycogen storage disease
  • defects in amino acid and fatty acid metabolism
  • Reye's syndrome
  • cyanotic congenital heart disease
  • hypopituatrism
  • isolated adrenocorticotropic hormone deficiency
  • Addison's disease
  • hereditary fructose intolerance
  • carnitine deficiency
  • defective type 1 glucose transporter in the brain
  • acquired liver disease
  • large non-beta cell tumor
  • sepsis
  • renal failure
  • congestive heart failure
  • starvation

 
Causes of pediatric hypoglycemia based on age
 Peri-natal
  • small for gestational age
  • premature infant
  • neonatal asphyxia or fetal distress
  • hypothermia
  • fetal-alcohol syndrome
  • mother taking hypoglycemia-inducing drugs
  • diabetic or pre-eclamptic mother
  • congenital heart disease
  • Beckwith-Wiedemann syndrome
  • erythroblastosis fetalis
  • infection
  • adrenal hemorrhage and adrenal insufficiency
 Infancy
  • starvation
  • idiopathic ketotic hypoglycemia
  • hypopituatrism
  • hypoadrenalism
  • hypothyroidism
  • growth hormone deficiency
  • inborn error of metabolism
  • amino acid metabolic abnormality
  • islet cell adenoma
  • islet cell hyperplasia
  • functional beta cell secretory defect
  • factitious insulin use or sulfonylurea use
  • Beckwith-Wiedemann syndrome
  • infection
  • hypothermia
  • congenital heart disease
 Childhood
  • idiopathic ketotic hypoglycemia
  • drug-induced (salicylate, alcohol)
  • islet cell adenoma
  • islet cell hyperplasia
  • factitious insulin or sulfonylurea use
  • Beckwith-Wiedemann syndrome
  • infection
  • hypothermia
  • large non-beta cell tumors
  • fulminant hepatic disease

 
Drugs associated with hypoglycemia
  • insulin, oral hypoglycemic agents
  • antibiotics - sulfonamides, isoniazid, pentamidine, trimethoprim, quinine, ketoconazole
  • analgesics - phenylbutazone, salicylates, propoxyphene, stanazol
  • cytoxic agents - methotrexate, 6 mercaptopurine
  • anticoagulants - bishydroxycoumarin
  • psychotropic drugs - ethanol, methanol, lithium haloperidol, tricyclic antidepressants, chlorpromazine, fluoxetine, 
  • insecticides - vapor rodenticide, carbamates, organophosphates
  • cardiac drugs - disopyramide, propanolol, thiazide diuretics, clofibrate, ACE inhibitors 

 
Differentiating insulinoma from factitious hyperinsulism
Cause Insulin level Pro-insulin level C-peptide level Other features
Insulinoma ++ ++ ++
  • during a prolonged fasting test, the glucose:insulin ratio decreases, and C-peptide levels are non-suppressed
  • no urine/plasma sulfonylurea detectable
Factitious hypoglycemia due to exogenous insulin ++++ - +/-
  •  serum insulin levels are usually very high
  • C-peptide levels are very low or undetectable
Factitious hypoglycemia due to sulfonylurea abuse ++ +/- ++
  • plasma/urine positive for sulfonylurea

Algorithm of causes of hypoglycemia in adults

Algorithm based on the critical blood sample in pediatric hypoglycemia

Disclaimer: My EM guidemaps reflect my personal approach to problem-solving/managing clinical cases in an ED setting and they should not be regarded as the standard of care. They merely represent the personal opinions of the author and they should only be used in clinical practice if the reader-user has substantial reason to believe that the clinical advice contained in the guidemaps is valid and accurate. The guidemaps are not meant to be "authoritative" and the reader-user should consult standard medical textbooks and expert opinion articles/guidelines for more authoritative advice. The reader-user should particularly confirm all drug doses, their indications and contra-indications, prior to their use.