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Whipples triad. Whipples triad refers to the presence of (1) symptoms, signs, or
both, consistent with hypoglycaemia; (2) low plasma glucose concentration; and (3)
resolution of the symptoms and/or signs with administration of glucose/after
glucose concentration is raised. The endocrine society recommends that only in
those with Whipples triad. Exception would be a patient who is unable to
communicate symptoms.
Symptoms of hypoglycaemia. Symptoms of hypoglycaemia develop at a mean
plasma glucose concentration of approximately 3 mmol/L. Symptoms of
hypoglycaemia can be divided into neuroglycopenic (a result of low glucose in
brain), and neurogenic (autonomic; symptoms and signs due to sympathoadrenal
discharge triggered by hypoglycaemia). Demonstration of a glucose level > 3.9
mmol/L is strong evidence that symptoms of a patient is not due to hypoglycaemia.
Biochemical workup in non-DM patient. The endocrine society recommends:
(1) Measurement of plasma glucose, insulin, C-peptide, proinsulin, and betahydroxybutyrate:
Glucose < 3 mmol/L, in the presence of one or more of below:
Insulin >= 3 mIU/L
C-peptide >= 0.2 nmol/L
Proinsulin >= 5 pmol/L
3-hydroxybutyrate <= 2.7 mmol/L
Indicates endogeneous hyperinsulinism;
(2) Observe the plasma glucose response to 1 mg of glucagon intravenously
Glucose rise of >= 1.4 mmol/L after IV glucagon indicate mediation by
insulin or by an IGF
(3) Screen for oral hypoglycaemic agent
(4) Formally re-create the circumstance which symptomatic hypoglycaemia
occurs:
Fasting, up to 72 hours After a mixed meal (a glucose tolerance test
should not be used)
(5) In patient where hyperinsulinaemic hypoglycaemia is confirmed:
Workup after (1) negative screen for OHA, (2) no circulating insulin
antibody
(6) Workup for hyperinsulinaemic hypoglycaemia:
Locate insulinoma by: CT, MRI, USG(transabdominal, endoscopic), ASVS
Causes of hypoglycaemia. Causes can be divided into where the subject is
ill/medicated or seemingly well. Where the subject is well, the diagnosis of
endogeneous hyperinsulinism (tumor, nesidioblastosis, dumping syndrome,
autoimmune insulin syndrome, secretagogue, etc), and accidental, surreptitious or
malicious causes should be considered. In addition to the above, in the ill or
medicated, the differential diagnosis includes drugs (insulin, OHA, alcohol, others#),
> 2-fold increase of insulin over baseline, or > 5 fold increase for contemporary
assays.
Insulin assay. Sandwich, particle-enhanced chemi-luminescent assay is used for
insulin in Abbott platform.