Investigations
1st investigations to order
serum glucose
Test
Measured when symptoms present or at the end of 72-hour fast, every 6 hours or at the onset of symptoms of hypoglycaemia confirmed by finger stick blood sugar of <50 mg/dL.
After glucagon administration at the end of 72-hour fast, glucose increase >1.4 mmol/L (>25 mg/dL) is consistent with insulinoma or insulin-like growth factor-II secretion.
Result
<2.8 mmol/L (<50 mg/dL)
liver function testing
Test
Ordered as a screening test once patient presents complaining of hypoglycaemic symptoms, to rule out hepatic causes (e.g., acute hepatitis, hepatic cirrhosis, hepatorenal syndrome).
Result
normal; abnormal when liver disease is the cause
renal function testing
Test
Ordered as a screening test once patient presents complaining of hypoglycaemic symptoms, to rule out renal causes (e.g., congestive heart failure, chronic renal failure, hepatorenal syndrome).
Result
normal; abnormal when renal disease is the cause
serum insulin
Test
Measured when glucose <3.3 mmol/L (<60 mg/dL) or at the end of 72-hour fast. Should be undetectable.
Elevated value is consistent with factitious hypoglycaemia or insulinoma.
Inappropriate elevation of C-peptide, proinsulin, and insulin suggest either insulinoma or sulfonylurea use.[34]
Result
>21 picomol/L (>3 microunits/mL)
serum C-peptide
Test
Measured when glucose level <3.3 mmol/L (<60 mg/dL) or at the end of 72-hour fast.
Elevated if insulin is endogenous. Inappropriate elevation of C-peptide, proinsulin, and insulin suggest either insulinoma or sulfonylurea use.[34]
Result
>200 picomol/L
serum beta-hydroxybutyrate
Test
Measured at the time of hypoglycaemic symptoms or at the end of 72-hour fast.
Excessive insulin or insulin-like growth factor-II inhibits ketogenesis and lowers beta-hydroxybutyrate.
Therefore, low beta-hydroxybutyrate would support diagnosis of mesenchymal tumour.
Result
<2.7 mmol/L
serum sulfonylurea
Test
Presence indicates iatrogenic hypoglycaemia. Test assays chlorpropamide, tolazamide, tolbutamide, glipizide, glyburide, acetohexamide, glimepiride, or gliclazide.
In the UK sulfonylurea screening is usually done on urine rather than serum, and both are valid options.
Result
positive
thyroid-stimulating hormone levels
Test
To rule out thyroid function disorders.
Result
normal; abnormal if thyroid dysfunction
serum cortisol
Test
Low level would indicate adrenal glands (primary) or hypopituitarism as source of adrenal insufficiency. To be confirmed by an adrenocorticotropic hormone stimulation test.
Result
may be below normal
Investigations to consider
48- to 72-hour fast under observation
Test
Indicated in adults if presence of hypoglycaemic symptoms but blood glucose >2.8 mmol/L (>50 mg/dL).
Blood glucose levels are checked every 6 hours. Once the blood sugar concentration by a finger stick is <3.3 mmol/L (<60 mg/dL), blood glucose levels should be checked every hour, along with serum proinsulin, C-peptide, and insulin levels.
The test ends upon any of the following occurrences: onset of sympathoadrenal or neuroglycopenic symptoms, blood glucose levels <2.8 mmol/L (<50 mg/dL), or conclusion of full 72 hours of fasting under observation.
Result
hypoglycaemia or sympathoadrenal or neuroglycopenic symptoms
oral glucose tolerance test
Test
It should be performed to rule out diabetes mellitus, as late reactive hypoglycaemia occurring within 3-5 hours after a meal can occur in some patients with prediabetes or impaired glucose tolerance, and during pregnancy.
Result
normal or low; 2-hour plasma glucose ≥11.1 mmol/L( ≥200 mg/dL) if diabetes mellitus
serum insulin-like growth factor (IGF)-II
Test
Used to confirm IGF-II hypersecretion if suspicion is raised by results of 72-hour fasting test. Patient need not be fasting.[41]
Result
>157 nanomol/L (1200 ng/mL)
serum adrenocorticotropic hormone
Test
Low level would suggest secondary or tertiary cause for adrenal insufficiency.
Result
below normal range
serum human growth factor (HGH)
Test
Low level suggests pituitary disorder.
Result
below normal
insulin suppression test
Test
Indicated in adults if presence of hypoglycaemic symptoms but blood glucose >2.8 mmol/L (>50 mg/dL).
Insulin 0.4 to 0.6 unit/kg is administered intravenously after an overnight fast. Blood sugar is assessed with a finger stick every 5 minutes. The blood glucose concentration should decline to <3.3 mmol/L (<60 mg/dL) within 15 to 25 minutes. At this time and in 5-minute intervals for 3 additional times, blood is drawn for serum glucose, C-peptide, cortisol, and HGH levels.
The patient is given 50 mL of 50% dextrose intravenously to aid in recovery at the end of the test.
Result
blood sugar decline
serum proinsulin
Test
Measured when glucose level <3.3 mmol/L (<60 mg/dL) or at the end of 72-hour fast.
Elevated if insulin is endogenous, especially with insulinoma. Inappropriate elevation of C-peptide, proinsulin, and insulin suggest either insulinoma or sulfonylurea use.[34]
Result
>5.0 picomol/L
CT scan abdomen and pelvis with and without intravenous contrast
Test
Order after non-factitious hypoglycaemia has been diagnosed. Imaging is sought to look for small islet cell tumours that could be responsible for an insulinoma or large tumours that may be producing IGF-II.[42]
Result
islet cell tumour
transabdominal ultrasound
Test
Order after non-factitious hypoglycaemia has been diagnosed and no tumours identified on CT scan. The ultrasound may be useful for detecting small islet cell tumours not seen on CT scan.
Result
islet cell tumour
endoscopic ultrasound
Test
This test should be ordered when both the CT scan and transabdominal ultrasound failed to identify the site of an insulinoma.[43]
Result
islet cell tumour
nuclear imaging with octreotide scan
Test
Corroborative test to identify a neuroendocrine tumour.
Result
positive
Use of this content is subject to our disclaimer