History and exam

Key diagnostic factors

common

diaphoresis

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

anxiety

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

tremor

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

hunger

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

generalised tingling

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

nausea

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

palpitations

Possible sympathoadrenal symptom of hypoglycaemia, 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 symptom; 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 hypoglycaemic 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 hypoglycaemia. Typically, only a significant component of hypoglycaemia in paediatric 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 hypoglycaemia. Typically, only a significant component of hypoglycaemia in paediatric 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 hypoglycaemia. Typically, only a significant component of hypoglycaemia in paediatric 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 hypoglycaemia. Typically, only a significant component of hypoglycaemia in paediatric cases.[26]

Risk factors

strong

middle age

True hypoglycaemia (i.e., fulfills Whipple's 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 hypoglycaemia was found to be more common in people aged over 65 years.[17]

insulinoma

Neuroendocrine tumour 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 hypoglycaemia.[31]

weak

female sex

True hypoglycaemia 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 hypoglycaemia requiring emergency medical services.[11]

bariatric surgery

Bariatric surgery causes abnormalities in stomach emptying (e.g., rapid transit of carbohydrates), which can lead to hypoglycaemia.[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 hypoglycaemia.[24]​​

fibromas

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

sarcomas

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

fibrosarcomas

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

adrenal insufficiency

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

growth hormone deficiency

Lack of a growth hormone response to low blood glucose levels may lead to failure to counteract hypoglycaemia. Typically, only a significant component of hypoglycaemia in paediatric 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 hypoglycaemia.[27]

glycogen storage diseases

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

anorexia nervosa

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

malnutrition

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

ackee fruit ingestion

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

haloperidol exposure

Known to weakly cause alpha-adrenergic blockade, thus possibly contributing to hypoglycaemia.[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 hypoglycaemia is not understood.[35]

beta-adrenergic-blocking agent exposure

Causes adrenergic blockade, which may sustain existing hypoglycaemia.[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 hypoglycaemia, sometimes requiring hospitalisation.[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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