List of causes of hypoglycemia

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This is a list of causes of hypoglycemia. Despite its length, it is not necessarily exhaustive, as new causes are reported regularly in the medical literature. In many individual instances of hypoglycemia, more than one contributing factor may be identifiable. In this list are some factors not usually sufficient to cause hypoglycemia by themselves. Some of these causes are represented by single case reports.

Causes of transient neonatal hypoglycemia

• Prematurity
• Intrauterine growth retardation
  • Smaller of twins
• Severe infant respiratory distress syndrome
• Maternal toxemia
• Perinatal asphyxia
• Critical illness

Starvation, inadequate intake or absorption

• Fasting, e.g. preoperative
• Severe malnutrition
• Kwashiorkor
• Anorexia nervosa
• Pyloric stenosis
• Vitamin B6 (pyridoxine) deficiency
• Biotin deficiency
• Hypomagnesemia
• Diarrhea
• Renal glycosuria
• Combined intestinal monosaccharide transport defect

Major organ failure and critical illness

• Congestive heart failure
• Cyanotic congenital heart disease
• Renal failure, especially chronic
  • Dialysis
• Central nervous system disorders
  • Head trauma
  • Stroke
  • Severe encephalopathies
  • Hypothalamic tumor
• Liver disorders
  • Severe acute hepatitis due to infection or toxins
  • Chronic liver failure
  • Reye's syndrome
  • HELLP syndrome (hemolysis, elevated liver enzymes, thrombocytopenia)
• Chronic pancreatitis
• Sepsis
• Hypothermia
• Malignant hyperthermia

Extrapancreatic tumors

• Mechanisms
  • Increased utilization by large or active tumor
  • Cachexia and depletion of glycogen reserves
  • Insulin-like peptides, especially IGF-II (Doege-Potter syndrome)
  • Inhibited hepatic gluconeogenesis or glycogenolysis
  • Blunted counterregulatory hormone responses
  • Autoimmune (see below)
• Tumors associated with hypoglycemia
  • Benign and malignant mesothelioma
  • Neurofibroma
  • Fibrosarcoma
  • Rhabdomyosarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Sarcomatous dysembryoma
  • Reticulum cell sarcoma
  • Hemangiopericytoma
  • Spindle cell sarcoma
  • Pseudomyxoma peritonei (Rosenfeld syndrome)
  • Hepatoma (Nadler Wolfer Elliott syndrome)
  • Adrenal carcinoma (Anderson syndrome)
  • Non-islet pancreatic carcinoma
  • Hypernephroma
  • Adenocarcinomas of prostate, colon, bile duct, breast, stomach
  • Simple fibroma
  • Leukemia
  • Lymphomas and Hodgkin's disease
  • Multiple myeloma
  • Wilms' tumor
  • Apudoma
  • Carcinoid tumors
  • Pheochromocytoma (especially after removal)
  • Melanoma
  • Teratoma
  • Neuroblastoma
  • Paraganglioma

Hyperinsulinism

• Hypoglycemia due to endogenous insulin
  • Congenital hyperinsulinism
    • Transient neonatal hyperinsulinism
      • Due to maternal factors
        • Maternal diabetes
        • Erythroblastosis fetalis
        • Excessive intravenous glucose during labor
        • Maternal sulfonylurea
        • Sympathomimetic tocolytic agents (e.g. ritodrine)
      • Due to infant factors
        • Intrauterine growth retardation
        • Perinatal asphyxia
        • Idiopathic transient hyperinsulinism
      • Iatrogenic
        • Malposition of umbilical catheter
    • Focal congenital hyperinsulinism
      • Paternal SUR1 mutation with clonal loss of heterozygosity of 11p15
      • Paternal Kir6.2 mutation with clonal loss of heterozygosity of 11p15
    • Diffuse congenital hyperinsulinism
      • Autosomal recessive forms
        • SUR1 mutations
        • Kir6.2 mutations
      • Autosomal dominant forms
        • Glucokinase gain-of-function mutations
        • Hyperammonemic hyperinsulinism (glutamate dehydrogenase gain-of-function mutations)
        • Loss of heterozygosity of 11p15 (Beckwith-Wiedemann syndrome)
    • Donohue syndrome (leprechaunism)
  • Acquired tumors and hyperplasias of pancreatic beta cells
    • Islet cell adenoma
    • Islet cell carcinoma
    • Multiple endocrine adenomatosis syndrome
    • Pluriglandular syndrome of islet, pituitary, parathyroid hyperplasia
  • Autoimmune insulin syndrome
  • Reactive hypoglycemia (postprandial hypoglycemia syndrome)
  • Dumping syndrome
• Drug induced hyperinsulinism
  • Oral hypoglycemic agents, especially Sulfonylureas
    • Treatment of diabetes
    • Treatment of diabetes insipidus
    • Ingestion by child
  • Aspirin overdose
  • Acetaminophen overdose
  • Pentamidine
  • Quinine
  • Disopyramide
  • Bordetella pertussis vaccine or infection
• Hypoglycemia due to exogenous (injected) insulin
  • Insulin self-injected for treatment of diabetes
    • Excessive insulin dosage or accelerated absorption
    • Excessive activity
    • Inadequate food or delayed or decreased absorption
    • Alcohol
    • Drugs which contribute synergistically
    • Development of concurrent disease
    • Acquired endocrinopathies
    • Renal, cardiac or liver failure
  • Factitious & malicious insulin injection
    • Insulin self-injected surreptitiously (e.g., Munchausen syndrome)
    • Munchausen by proxy
  • Insulin tolerance test for pituitary or adrenergic response assessment
  • Treatment of hyperkalemia
  • Insulin potentiation treatment (cancer quackery)
  • Insulin-induced coma for depression or psychosis treatment (insulin shock)

Hormone deficiencies

• Cortisol
  • Addison's disease (acquired adrenal destruction)
  • ACTH deficiency
  • ACTH unresponsiveness
  • Congenital adrenal hypoplasia
  • Congenital adrenal hyperplasia
• Growth hormone
  • Isolated growth hormone deficiency
  • Laron dwarfism (GH unresponsiveness)
• Epinephrine and catecholamines
  • Adrenomedullary unresponsiveness
• Glucagon
• Combined deficiencies
  • Congenital hypopituitarism (various causes)
  • Psychosocial deprivation syndrome (hypothalamic)
  • Thyroid hormone (depresses GH and ACTH)

Metabolic Defects

• Defective glycogenolysis or glycogen accumulation
  • Glucose-6-phosphatase deficiency (glycogenosis type I, von Gierke dis)
  • Pseudoglycogenosis type I
  • Amylo-1,6-glucosidase (debrancher) deficiency (glycogenosis type III)
  • Hepatic phosphorylase deficiency (glycogenosis type VI)
  • Hepatic phosphorylase kinase deficiency (glycogenosis type IXb)
  • Glycogen synthase deficiency (glycogenosis type 0)
• Galactose-1-phosphate uridyl transferase deficiency (galactosemia)
• Defects of gluconeogenesis or substrate supply
  • Fructose-1,6-diphosphatase deficiency
  • Isovaleric acidemia
  • Hypoalaninemia^{needs reference}
  • Phosphoenolpyruvate carboxykinase deficiency
  • Pyruvate carboxylase deficiency (Leigh syndrome)
  • Fructose-1-phosphate aldolase deficiency
• Defects of mitochondrial beta-oxidation and fatty acid metabolism
  • Systemic carnitine deficiencies
    • Enzyme deficiencies
    • Carnitine palmitoyltransferase I
    • Carnitine palmitoyltransferase II
    • Carnitine acyltransferase
  • Butyryl CoA dehydrogenase
  • Hydroxymethylglutaryl CoA lyase
  • Methylcrotonyl CoA carboxylase
  • Medium chain acyl CoA dehydrogenase
  • Short chain acyl CoA dehydrogenase
  • Long chain acyl CoA dehydrogenase
  • Multiple acyl CoA dehydrogenase (glutaric aciduria type II)
  • Long-chain 3-hydroxyacyl-CoA dehydrogenase
  • Short-chain 3-hydroxyacyl CoA dehydrogenase
  • Carnitine/acylcarnitine translocase
• Enoyl CoA hydratase
• Ketothiolase
• Succinyl CoA:acetoacetate transferase
• Defects of amino acid metabolism
  • Maple syrup urine disease
  • Methylmalonic acidemia
  • [[hydroxy-methylglutaric aciduria]]
  • Tyrosinosis
  • Phenylketonuria
  • Propionic acidemia
• Miscellaneous metabolic defects
  • Defective type I glucose transporter in brain
  • Methylglutaconic aciduria
  • Sucrosuria
  • Glycerol intolerance
  • Rare variants of galactose intolerance
  • Other rare or poorly defined congenital metabolic defects

Drugs and toxic substances

• Insulin, antidiabetic agents (see above)
• Drugs associated with hypoglycemia alone
  • Ethanol
  • Beta blockers, e.g. propranolol
  • Salicylates
  • Acetaminophen
  • Acetazolamide
  • Aluminium hydroxide
  • Chloroquine
  • Chlorpromazine
  • Cimetidine, ranitidine
  • Diphenhydramine, other antihistamines
  • Propoxyphene
  • Disopyramide
  • Doxepin
  • Golytely (in distal intestinal obstruction syndrome of cystic fibrosis)
  • Imipramine
  • Indometacin
  • Isoxsuprine
  • Insulin-like growth factor 1
  • Lidocaine
  • Lithium
  • Pentamidine
  • Propranolol, nadolol, labetalol, metoprolol
  • Orphenadrine
  • Oxytetracycline
  • Quinine, quinidine
  • Perhexiline
  • Ritodrine
  • Haloperidol
  • Chelating agents (BAL and EDTA)
  • THAM
  • Colchicine
  • Para amino benzoic acid, para-amino salicylic acid
  • Cholestyramine added during glucocorticoid therapy (reduces absorption)
• Drugs which lower glucose in diabetics
  • Enalapril and captopril
  • Coumarin
  • Phenylbutazone
  • Antihistamines
  • Sulfa antibiotics, including SMX/TMP (especially in renal failure)
  • Monoamine oxidase inhibitors
  • Medicines not available in U.S.
    • Azapropazone, buformin, carbutamide, cibenzoline, cycloheptolamide, glibornuride, gliclazide, mebanazine, metahexamide, perhexiline, sulphadimidine, sulphaphenazole, Nigerian cow urine medicine
• Environmental toxins
  • Amanita phalloides toxin
  • Abractylis gummifera (Mediterranean plant)
  • Hypoglycin from unripe Ackee fruit (Jamaican vomiting illness)
  • Parathion
  • Vacor rat poison

Idiopathic and miscellaneous

• Ketotic hypoglycemia
  • Identifiable hormone and enzyme deficiencies
• Idiopathic
  • Idiopathic hypoglycemias, etiologies undetermined
  • Autoimmune
  • Antibodies to insulin
  • Antibodies to insulin receptor
  • Stimulating antibodies to islet cells
  • Thyrotoxicosis (extremely rare)
  • Infection
    • Mumps
    • Varicella
    • Pertussis
    • Measles
    • Malaria
• Extreme exercise
• Artifactual
  • In vitro glucose consumption after blood drawing
  • Leukemic WBC's may consume glucose in vitro
  • Polycythemia of infancy (RBCs consume glucose in vitro)
  • Inaccuracies of blood drop strips
  • Inherent variation inaccuracy at low end
  • Inadequate drop
  • Excessive wiping
  • Short time interval

Reactive, functional, postprandial, etc.

• Prediabetes (both categories controversial & may not be valid)
  • Juvenile diabetes (rare, anecdotal reports)
  • Adult onset diabetes (in early stages)
• After intravenous glucose load
• Abrupt discontinuation of parenteral nutrition or i.v. glucose
• After exchange transfusion with ACD preserved blood in neonate
• Alimentary (rapid jejunal emptying with exaggerated insulin response)
• Post fundoplication for gastroesophageal reflux
• Post gastrectomy dumping syndrome
• Short bowel syndrome
• Idiopathic gastrointestinal motility disturbance
• Alternate day growth hormone therapy
• Idiopathic reactive or postprandial hypoglycemia (hypoglycemia documented at time of symptoms: rare)
• Idiopathic postprandial syndrome (hypoglycemia never documented: common)