Hypoglycemia causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Causes

Causes by Organ System

Cardiovascular	No underlying causes
Chemical / poisoning	1,1-Dichloroethene, ackee fruit food poisoning, clove, ethanol, ginsen, jamaican vomiting sickness, systemic monochloroacetate poisoning
Dermatologic	No underlying causes
Drug Side Effect	Acetohexamide, amprenavir, chloramphenicol, chlorpromazine, chlorpropamide, cidofovir, cibenzoline, dipeptidyl peptidase-4 inhibitor, empagliflozin, ethanol, ethionamide, fluorodeoxyglucose, gatifloxacin, ginseng, glibenclamide, gliclazide, glimepiride, glipizide, gliquidone, glisolamide, glisoxepide, glyburide, insulin aspart, insulin detemir, insulin glargine, insulin-like growth factor, lanreotide, levomepromazine, levobunolol hydrochloride, linagliptin, lorcaserin, mecasermin, meropenem, mitiglinide, nateglinide, nitisinone, oxcarbazepine, pazopanib, pegvisomant, penicillamine, pentamidine isethionate, perazine, pipothiazine, pramipexole, pramlintide, quinine, repaglinide, rifaximin, ritonavir, saxagliptin, saquinavir, sertraline, somatostatin, sulfamethoxazole, temafloxacin, thalidomide, tolazamide, tolbutamide, trimethoprim, vildagliptin, zonisamide
Ear Nose Throat	No underlying causes
Endocrine	Addison's disease, ACTH deficiency, adrenal cancer, adrenal cortex insufficiency, adrenal insufficiency, autoimmune adrenalitis, congenital hyperinsulinism, diabetes mellitus type 1, diabetes mellitus type 2, diabetic gastroparesis, functioning pancreatic endocrine tumor, glucocorticoid deficiency 1, growth hormone deficiency, hyperinsulinism, hyperinsulinism due to glutamodehydrogenase deficiency,hypopituitarism, hypoglycemia, hypothyroidism, hypopituitarism, islet cell adenoma, insulin, insulinoma, idiopathic growth hormone deficiency, ketotic hypoglycemia, multiple endocrine neoplasia type 1, myxedema coma, nesidioblastosis, pancreatic cancer, pituitary dwarfism II, sheehan's syndrome, timme syndrome, tyrosinemia, Wilms tumor
Environmental	No underlying causes
Gastroenterologic	Acute fatty liver of pregnancy, acute liver failure, cirrhosis, diabetic gastroparesis, diarrhea, dumping syndrome, functioning pancreatic endocrine tumor, gastric dumping syndrome, hepatic congestion, hepatic failure, idiopathic postprandial syndrome, Insulinoma, liver cancer, malabsorption, maldigestion, reactive hypoglycemia, severe hepatitis
Genetic	2-methylbutyryl-coenzyme A dehydrogenase deficiency, 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency, 3-Methylcrotonyl-CoA carboxylase deficiency, ACAD9 deficiency, adrenal hypoplasia congenital, X-linked, acetohexamide, aldolase A deficiency, alpers syndrome, Beckwith-Weidemann Syndrome carbohydrate-deficient glycoprotein syndrome type 1b, carnitine palmitoyltransferase 1 deficiency, carnitine-acylcarnitine translocase deficiency, Coenzyme Q cytochrome c reductase deficiency, cleft lip palate pituitary deficiency, debrancher deficiency, dicarboxylicaminoaciduria, dihydrolipoamide dehydrogenase deficiency, Donohue syndrome, dopamine beta hydroxylase deficiency, familial glucocorticoid deficiency, familial hyperinsulinemic hypoglycemia type 3, familial hyperinsulinemic hypoglycemia type 5, familial hyperinsulinemic hypoglycemia type 7, fructose-1,6-bisphosphatase deficiency, fructose-1-phosphate aldolase deficiency, galactose-1-phosphate uridyltransferase deficiency, glucose 6 phosphate dehydrogenase deficiency, glutaric acidemia type 2, glucokinase mutations, glycogenosis type 1a, glycogenosis type 1b, glycogenosis type 3, glycogenosis type 6, glycogenosis type 9a, glycogenosis type 9b, glycogenosis type 9c, glycogenosis type V, growth hormone deficiency, hereditary ACTH resistance, hepatocyte nuclear factor 1a, HMG-CoA lyase deficiency, hydroxymethylglutaryl-CoA lyase deficiency, hyperinsulinism-hyperammonemia syndrome, KATP channel defects, Laron dwarfism, Leucine-induced hypoglycaemia, liver glycogen synthase deficiency, malonyl-CoA decarboxylase deficiency, maple syrup urine disease, medium chain acyl-CoA dehydrogenase deficiency, methylmalonic acidemia, mitochondrial DNA depletion syndrome, hepatocerebral form, mitochondrial trifunctional protein deficiency, monocarboxylate transporter 1,navajo neurohepatopathy, nesidioblastosis, paternal uniparental disomy, Plasma membrane carnitine transporter deficiency, Propionyl-CoA carboxylase deficiency PCCA type, propionic acidemia, primary carnitine deficiency, pyruvate carboxylase deficiency, Short chain acyl-CoA dehydrogenase deficiency, triple A syndrome, tyrosinaemia type 1, uncoupling protein 2, very long-chain acyl-CoA dehydrogenase deficiency, septic shock
Hematologic	Hemolytic disease of the newborn
Iatrogenic	Gastrojejunostomy, gastric dumping syndrome, postgastrectomy syndrome, pyloroplasty, Reye syndrome
Infectious Disease	Acute meningitis, malaria, neonatal bacterial meningitis, Reye's syndrome, sepsis, visceral leishmaniasis
Musculoskeletal / Ortho	No underlying causes
Neurologic	Acute meningitis, autonomic dystonia, autonomic neuropathy, elevated vagal tone, Reye's syndrome
Nutritional / Metabolic	Acetohexamide, ACAD9 deficiency, binge drinking, coenzyme Q cytochrome c reductase deficiency, deficiency in enzymes of fat oxidation, diabetes mellitus, diabetic gastroparesis, dicarboxylic aminoaciduria, fructose intolerance, galactosemia, glycogen debranching deficiency, glucose-6-phosphatase deficiency, hypoketonemic hypoglycemia, Ketotic hypoglycemia of infancy, Mcquarrie type infantile idiopathic hypoglycemia, organic acidemia, pyruvate carboxylase deficiency, phosphoenolpyruvate carboxykinase (PEPCK) deficiency, Urea cycle disorder, Glucagon deficiency, fructose-1, 6-diphosphatase deficiency, Fructose intolerance, Fructose-1,6-bisphosphatase deficiency, hereditary, galactosemia,fructose-1-phosphate aldolase deficiency, glucose 6 phosphate dehydrogenase deficiency, glutaric acidemia type 2, glycogenosis type 1a, glycogenosis type 1b, glycogenosis type 3, glycogenosis type 6, glycogenosis type 9a, glycogenosis type 9b, glycogenosis type 9c, glycogenosis type V, HMG-CoA lyase deficiency, HMG CoA synthetase deficiency,hydroxymethylglutaryl-CoA lyase deficiency, inborn urea cycle disorder, leucinosis, long chain hydroxyacyl-CoA dehydrogenase deficiency, malabsorption, malonic aciduria,malonyl-CoA decarboxylase deficiency, maple syrup urine disease, medium chain acyl-CoA dehydrogenase deficiency, Methylmalonic acidemia, Nesidioblastosis, organic acidemia, propionic acidemia, propionyl-CoA carboxylase deficiency PCCA type, reactive hypoglycemia, short chain acyl-CoA dehydrogenase deficiency, tyrosinaemia type 1, very long-chain acyl-CoA dehydrogenase deficiency
Obstetric/Gynecologic	Diabetic mother, Gestational diabetes, Intrauterine growth retardation, Pregnancy, Premature labour and/or delivery, Sheehan syndrome, Acute fatty liver of pregnancy,Hemolytic disease of the newborn
Oncologic	Adrenal cancer, breast cancer, Doege-potter syndrome, IGF producing tumors, tumors, pancreatic cancer, insulinoma, liver cancer, mesothelioma, metastatic insulinoma fasting
Opthalmologic	No underlying causes
Overdose / Toxicity	Acetohexamide, amprenavir, chloramphenicol, chlorpromazine, chlorpropamide, cibenzoline, clove, ethanol, ethionamide, fluorodeoxyglucose, gatifloxacin, ginseng, glibenclamide, gliclazide, glimepiride, glipizide, gliquidone, glisolamide, glisoxepide, insulin, insulin like growth factor , lanreotide, levomepromazine, mitiglinide, nateglinide, pazopanib, pentamidine, perazine, pipothiazine, pramlintide, quinine, repaglinide, ritonavir, saquinavir, somatostatin, sulfamethoxazole, temafloxacin, tolazamide, tolbutamide, trimethoprim
Psychiatric	Anorexia nervosa, Bullimia nervosa, Munchausen syndrome, factitious hypoglycemia
Pulmonary	Mesothelioma
Renal / Electrolyte	Benign glucosuria, renal Failure, renal hypoglycemia, uremia
Rheum / Immune / Allergy	Autoimmune adrenalitis, hemolytic disease of the newborn, immunopathologic hypoglycemia, insulin receptor antibodies
Sexual	No underlying causes
Trauma	Burns
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Alcoholism, Binge drinking, Cachexia, Delayed separation blood sample, Drip arm sample, Fasting , Heavy exercise, Hypothermia, Idiopathic hypoglycemia, Starvation (acute), Mcquarrie type infantile idiopathic hypoglycemia, Burns, Ethanol

Causes in Alphabetical Order

1,1-Dichloroethene 2-methylbutyryl-coenzyme A dehydrogenase deficiency 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency ACAD9 deficiency Acetohexamide Ackee fruit Acute fatty liver of pregnancy Acute liver failure Acute meningitis Addison's disease Adrenal cancer Adrenal cortex insufficiency Adrenal insufficiency Alcoholism Alpers Syndrome Amprenavir Anorexia nervosa Autoimmune adrenalitis Autonomic dystonia Autonomic neuropathy Beginning stages of diabetes Benign glucosuria Binge drinking Bullimia nervosa Burns Cachexia Carbohydrate-deficient glycoprotein syndrome type 1b Carnitine palmitoyltransferase 1 deficiency Carnitine-acylcarnitine translocase deficiency Chloramphenicol Chlorpromazine Chlorpropamide Cidofovir Cibenzoline Cirrhosis Cleft lip palate pituitary deficiency Clove Coenzyme Q cytochrome c reductase deficiency Deficiency in enzymes of fat oxidation Delayed separation blood sample Diabetic gastroparesis Diabetic mother Diarrhea Dicarboxylicaminoaciduria Dihydrolipoamide dehydrogenase deficiency Doege-Potter syndrome Donohue syndrome Dopamine beta-hydroxylase deficiency Drip arm sample Dumping syndrome Elevated vagal tone Ethanol Ethionamide Familial glucocorticoid deficiency Familial hyperinsulinemic hypoglycemia type 3 Familial hyperinsulinemic hypoglycemia type 5 Familial hyperinsulinemic hypoglycemia type 7 Fasting Fluorodeoxyglucose Fructose intolerance Fructose-1, 6-diphosphatase deficiency Fructose-1-phosphate aldolase deficiency Functioning pancreatic endocrine tumor Galactose-1-phosphate uridyltransferase deficiency Galactosemia Gastric dumping syndrome Gastrojejunostomy Gatifloxacin Gestational diabetes Ginseng Glibenclamide Gliclazide Glimepiride Glipizide Gliquidone Glisolamide Glisoxepide Glucagon deficiency Glucose 6 phosphate dehydrogenase deficiency Glutaric acidemia type 2 Glycogen debranching deficiency Glycogenosis type 1a Glycogenosis type 1b Glycogenosis type 3 Glycogenosis type 6 Glycogenosis type 9a Glycogenosis type 9b Glycogenosis type 9c Glycogenosis type V Growth hormone deficiency (congenital) Heavy exercise Hemolytic disease of the newborn

Hepatic congestion Hepatic failure Hereditary ACTH resistance HMG-CoA lyase deficiency Hydroxymethylglutaryl-CoA lyase deficiency Hyperinsulinism-hyperammonemia syndrome Hypoketonemic hypoglycemia Hypopituitarism Hypothermia Hypothyroidism Idiopathic hypoglycemia Idiopathic postprandial syndrome IGF producing tumors Immunopathologic hypoglycemia Insulin Insulin like growth factor Insulin lispro Insulin receptor antibodies Insulinoma Intrauterine growth retardation Jamaican vomiting sickness Janumet (sitagliptin and metformin) Ketotic hypoglycemia of infancy Lanreotide Laron dwarfism Leucine-induced hypoglycaemia Levomepromazine Liver cancer Liver glycogen synthase deficiency Long chain hydroxyacyl-CoA dehydrogenase deficiency Malabsorption Malaria (malignant tertian) Maldigestion Malonyl-CoA decarboxylase deficiency Maple syrup urine disease Mcquarrie type infantile idiopathic hypoglycemia Medium chain acyl-CoA dehydrogenase deficiency Mesothelioma Methylmalonic acidemia Mitiglinide Mitochondrial DNA depletion syndrome, hepatocerebral form Mitochondrial trifunctional protein deficiency Multiple endocrine neoplasia Munchausen syndrome Myxedema coma Nateglinide Navajo neurohepatopathy Nephroblastomatosis-fetal ascites-macrosomia-wilms tumor Nesidioblastosis Organic acidemia Pazopanib Pentamidine Perazine Phosphoenolpyruvate carboxykinase (PEPCK) deficiency Pipothiazine Plasma membrane carnitine transporter deficiency Postgastrectomy syndrome Pramlintide Pregnancy Premature labour and/or delivery Propionyl-CoA carboxylase deficiency PCCA type Pyloroplasty Quinine Reactive hypoglycemia Renal Failure Renal hypoglycemia Repaglinide Reye syndrome Ritonavir Saquinavir Sepsis Septic shock Severe hepatitis Sheehan syndrome Short chain acyl-CoA dehydrogenase deficiency Short stature-pituitary and cerebellar defects-small sella turcica Somatostatin Starvation (acute) Sulfamethoxazole Systemic monochloroacetate poisoning Temafloxacin Timme syndrome Tolazamide Tolbutamide Trimethoprim Triple A syndrome Tumors Tyrosinaemia type 1 Urea cycle disorder Uremia Very long-chain acyl-CoA dehydrogenase deficiency Visceral leishmaniasis Wiedemann-Beckwith syndrome X-linked congenital adrenal hypoplasia

Causes

Common Causes

Hypoglycemia in Newborn Infants

Hypoglycemia is a common problem in critically ill or extremely low birthweight infants. If not due to maternal hyperglycemia, in most cases it is multifactorial, transient and easily supported. In a minority of cases hypoglycemia turns out to be due to significant hyperinsulinism, hypopituitarism or an inborn error of metabolism and presents more of a management challenge.

• Transient neonatal hypoglycemia
  • Prematurity, intrauterine growth retardation, perinatal asphyxia
  • Maternal hyperglycemia due to diabetes or iatrogenic glucose administration
  • Sepsis
  • Prolonged fasting (e.g., due to inadequate breast milk or condition interfering with feeding)
• Congenital hypopituitarism
• Congenital hyperinsulinism, several types, both transient and persistent
• Inborn errors of carbohydrate metabolism such as glycogen storage disease

Hypoglycemia in Young Children

Single episodes of hypoglycemia due to gastroenteritis or fasting, but recurrent episodes nearly always indicate either an inborn error of metabolism, congenital hypopituitarism, or congenital hyperinsulinism

• Prolonged fasting
  • Diarrheal illness in young children, especially rotavirus gastroenteritis
• Idiopathic ketotic hypoglycemia
• Isolated growth hormone deficiency, hypopituitarism
• Insulin excess
  • Hyperinsulinism due to several congenital disorders of insulin secretion
  • Insulin injected for type 1 diabetes
• Gastric dumping syndrome (after gastrointestinal surgery)
• Other congenital metabolic diseases; some of the common include
  • Maple syrup urine disease and other organic acidurias
  • Type 1 glycogen storage disease
  • Disorders of fatty acid oxidation
  • Medium chain acylCoA dehydrogenase deficiency (MCAD)
• Accidental ingestions
  • Sulfonylureas, propranolol and others
  • Ethanol (mouthwash, "leftover morning-after-the-party drinks")

Hypoglycemia in Older Children and Young Adults

By far the most common cause of severe hypoglycemia in this age range is insulin injected for type 1 diabetes. Circumstances should provide clues fairly quickly for the new diseases causing severe hypoglycemia. All of the congenital metabolic defects, congenital forms of hyperinsulinism, and congenital hypopituitarism are likely to have already been diagnosed or are unlikely to start causing new hypoglycemia at this age. Body mass is large enough to make starvation hypoglycemia and idiopathic ketotic hypoglycemia quite uncommon. Recurrent mild hypoglycemia may fit a reactive hypoglycemia pattern, but this is also the peak age for idiopathic postprandial syndrome, and recurrent "spells" in this age group can be traced to orthostatic hypotension or hyperventilation as often as demonstrable hypoglycemia.

• Insulin-induced hypoglycemia
  • Insulin injected for type 1 diabetes
  • Factitious insulin injection (Munchausen syndrome)
  • Insulin-secreting pancreatic tumor
  • Reactive hypoglycemia and idiopathic postprandial syndrome
• Addison's disease
• Sepsis

Hypoglycemia in Older Adults

The incidence of hypoglycemia due to complex drug interactions, especially involving oral hypoglycemic agents and insulin for diabetes rises with age. Though much rarer, the incidence of insulin-producing tumors also rises with advancing age. Most tumors causing hypoglycemia by mechanisms other than insulin excess occur in adults.

• Insulin-induced hypoglycemia
  • Insulin injected for diabetes
  • Factitious insulin injection (Munchausen syndrome)
  • Excessive effects of oral diabetes drugs, beta-blockers, or drug interactions, Tiagabine
  • Insulin-secreting pancreatic tumor
  • Alimentary (rapid jejunal emptying with exaggerated insulin response)
    • After gastrectomy dumping syndrome or bowel bypass surgery or resection
  • Reactive hypoglycemia and idiopathic postprandial syndrome
• Tumor hypoglycemia, Doege-Potter syndrome
• Acquired adrenal insufficiency
• Acquired hypopituitarism
• Immunopathologic hypoglycemia

References

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