Insulinoma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2]

Overview

Insulinoma must be differentiated from other diseases that cause features of hypoglycemia like altered mental status/confusion, profuse sweating and visual disturbances (blurring/diplopia). These are classified on the basis of laboratory findings into exogenous insulin, oral hypoglycemic agents (e.g. sulphonylureas), nesidioblastosis, insulin autoimmune hypoglycemia.

Differentiating insulinoma from other Diseases

• Insulinoma must be differentiated from other diseases that cause features of hypoglycemia. These are classified on the basis of laboratory findings.

Differentials for Hypoglycemia on the basis of Laboratory findings:

Diagnoses	Laboratory Findings differentiating among causes of Hypoglycemia
	S.Glucose (mg/dL)	C Peptide (pmol/L)	S.Insulin (μU/mL)	S.Proinsulin (pmol/L)	S. Beta hydroxybutyrate	Glucose increase after glucagon(mg/dL)	Oral Hypoglycemic agent	Antibodies to Insulin
Normal/Fasting	<55	<200	<3	<5	>2.7	<25	-	-
Exogenous Insulin	<55	<200	>>3	<5	≤2.7	>25	-	-
Insulinoma/Nesidioblastosis/PGPH†	<55	≥200	≥3	≥5	≤2.7	>25	-	-
Insulin autoimmune hypoglycemia	<55	>>200‡	>>3	>>5‡	≤2.7	>25	-	+
Oral hypoglycemic agent	<55	≥200	≥3	≥5	≤2.7	>25	+	-
IGF¤	<55	<200	<3	<5	≤2.7	>25	-	-

† PGPH= Post Gastric Bypass Hypoglycemia,
‡ Free C-peptide and proinsulin concentrations are low
¤ IGF= Insulin Growth Factor, Increased pro-IGF-2, free IGF-2, IGF-2/IGF-1 ratio

Differentiating hypoglycemia from other diseases that cause autonomic hyperactivity symptoms (tachycardia, hypertension):

Disease	Clinical Manifestation					Investigations
	Symptoms				Signs
	Tachycardia	Fever	Sweating	Headache
Anxiety disorders	+	-	+	+	Patient looks irritable Rapid pulse and may be irregular	Normal investigations
Pheochromocytoma	+	+	+	+	Tachycardia Strong rapid pulse High pulse pressure	Plasma fractionated metanephrines, 24-hour urinary fractionated metanephrines, catecholamines. Computed tomography: Radiological evaluation should follow lab tests to locate site of the tumour.
Arrhythmia	+	-	-	-	Irregular pulse	ECG changes according to the cause
Hyperthyroidism	+	+	+	+	Hyperactive deep tendon reflexes Thyromegaly Exophthalmus	Level of thyroid-stimulating hormone (TSH) Levels of T4 and/or T3 in the blood Antibodies such as anti-TSH-receptor antibodies in Graves' disease