History and exam

Key diagnostic factors

common

diaphoresis

Possible sympathoadrenal symptom of hypoglycemia, although constellation of several symptoms is more specific than any one symptom alone.[15]

anxiety

Possible sympathoadrenal symptom of hypoglycemia, although constellation of several symptoms is more specific than any one symptom alone.[15]

tremor

Possible sympathoadrenal symptom of hypoglycemia, although constellation of several symptoms is more specific than any one symptom alone.[15]

hunger

Possible sympathoadrenal symptom of hypoglycemia, although constellation of several symptoms is more specific than any one symptom alone.[15]

generalized tingling

Possible sympathoadrenal symptom of hypoglycemia, although constellation of several symptoms is more specific than any one symptom alone.[15]

nausea

Possible sympathoadrenal symptom of hypoglycemia, although constellation of several symptoms is more specific than any one symptom alone.[15]

palpitations

Possible sympathoadrenal symptom of hypoglycemia, although constellation of several symptoms is more specific than any one symptom alone.[15]

confusion

Possible neuroglycopenic symptom; the constellation of several symptoms is more specific than any one symptom alone.

irritability

Possible neuroglycopenic symptoms, the constellation of several symptoms is more specific than any one symptom alone.

blurred vision

Possible neuroglycopenic symptom; the constellation of several symptoms is more specific than any one symptom alone.

drowsiness

Possible neuroglycopenic symptom; the constellation of several symptoms is more specific than any one symptom alone.

Other diagnostic factors

uncommon

unexplained weight gain

When present with hypoglycemic symptoms, may suggest insulinoma.[7]

unexplained weight loss

May suggest adrenal insufficiency.

Lack of a cortisol response to low serum glucose levels may lead to failure to counteract hypoglycemia. Typically, only a significant component of hypoglycemia in pediatric cases.[26]

hyperpigmentation

Typically, in folds and scars and includes areas not exposed to sun.

May suggest adrenal insufficiency.

Lack of a cortisol response to low serum glucose levels may lead to failure to counteract hypoglycemia. Typically, only a significant component of hypoglycemia in pediatric cases.[26]

hypotension

Frank hypotension or orthostatic hypotension.

May suggest adrenal insufficiency.

Lack of a cortisol response to low serum glucose levels may lead to failure to counteract hypoglycemia. Typically, only a significant component of hypoglycemia in pediatric cases.[26]

short stature

Possible growth hormone deficiency; may also be asymptomatic.

Lack of a growth hormone response to low serum glucose levels may lead to failure to counteract hypoglycemia. Typically, only a significant component of hypoglycemia in pediatric cases.[26]

Risk factors

strong

middle age

True hypoglycemia (i.e., fulfills Whipple triad) in people without diabetes mellitus more commonly affects those who are middle-aged.[16]​​ In one retrospective cohort of inpatients outside of critical care, non-diabetic hypoglycemia was found to be more common in people ages over 65 years.[17]

insulinoma

Neuroendocrine tumor that secretes insulin in an unregulated fashion.[7]

exogenous insulin

Incorrect dosage of insulin, intentional overdose of insulin, or correct dosage of insulin but decreased food intake may cause hypoglycemia.[31]

weak

female sex

True hypoglycemia in people without diabetes mellitus has a slight female predominance.​[16][18]

ethanol consumption

Heavy alcohol consumption decreases hepatic production of glucose.[19] In one study, alcohol-use disorder was the most common cause of non-diabetic hypoglycemia requiring emergency medical services.[11]

bariatric surgery

Bariatric surgery causes abnormalities in stomach emptying (e.g., rapid transit of carbohydrates), which can lead to hypoglycemia.[20][21]​ Nesidioblastosis/islet hypertrophy has been reported after bariatric surgery.[8]

liver failure

Hepatic failure may result in depleted glycogen stores and impaired gluconeogenesis.[22]

renal failure

Renal failure may impair gluconeogenesis.[23]

intense exercise

Exercise induces glucose uptake independent of insulin receptors and if intense enough can lead to hypoglycemia.[24]​​

fibromas

Large tumors of mesenchymal origin can secrete insulin-like growth factor-II, an insulin-like compound, in an unregulated fashion and result in hypoglycemia.

sarcomas

Large tumors of mesenchymal origin can secrete insulin-like growth factor-II, an insulin-like compound, in an unregulated fashion and result in hypoglycemia.

fibrosarcomas

Large tumors of mesenchymal origin can secrete insulin-like growth factor-II, an insulin-like compound, in an unregulated fashion and result in hypoglycemia.

adrenal insufficiency

Lack of a cortisol response to low blood glucose levels may lead to failure to counteract hypoglycemia. Typically, only a significant component of hypoglycemia in pediatric cases.[25]

growth hormone deficiency

Lack of a growth hormone response to low blood glucose levels may lead to failure to counteract hypoglycemia. Typically, only a significant component of hypoglycemia in pediatric cases.[26]

hypopituitarism

Failure of the hypothalamic-pituitary axis may lead to deficient growth hormone and adrenocorticotropic hormone secretion.[25]

sepsis

End-organ damage and a heightened metabolic demand may predispose to hypoglycemia.[27]

glycogen storage diseases

Lack of stored glycogen hinders production of glucose to counteract hypoglycemia.[28]

anorexia nervosa

Chronic malnourishment results in paucity of glycogen stores needed to counteract hypoglycemia.[29][30]

malnutrition

Chronic malnourishment results in paucity of glycogen stores needed to counteract hypoglycemia.[30]

ackee fruit ingestion

Ingestion of unripened ackee fruit in a malnourished individual can cause hypoglycemia due to the effects of hypoglycin toxins on gluconeogenesis.[9]

haloperidol exposure

Known to weakly cause alpha-adrenergic blockade, thus possibly contributing to hypoglycemia.[32]

quinine exposure

Quinine or fluoroquinolone may cause excess secretion of insulin. Mechanism is poorly understood.[33]

fluoroquinolone exposure

Quinine or fluoroquinolone may cause excess secretion of insulin. Mechanism is poorly understood.[33]

sulfonylurea exposure

Directly stimulates secretion of insulin regardless of blood glucose levels.[34]

disopyramide exposure

Mechanism causing hypoglycemia is not understood.[35]

beta-adrenergic-blocking agent exposure

Causes adrenergic blockade, which may sustain existing hypoglycemia.[35]

salicylate exposure

Overdose of salicylates may cause an increase in the insulin response.[4]

tramadol exposure

Tramadol therapy is associated with an increased risk of hypoglycemia, sometimes requiring hospitalization.[14][36]

proton pump inhibitor exposure

Proton pump inhibitors (e.g., pantoprazole) have been found to have a glucose-lowering effect; however, further research is required.[3]

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