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	<55	≥200	≥3	≥5	≤2.7	>25	-	-
Nesidioblastosis
Post gastric bypass hypoglycemia (PGPH)
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	-	-
‡ 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 :

Disease	Clinical Manifestation					Investigations
	Symptoms				Signs
	Palpitations	Fever	Sweating	Headache
Hypoglycemia	+	-	+	+	Tachycardia Blurred vision Pallor Tremors Seizures/ Coma	Plasma glucose <70 mg/dL S. Insulin S. Proinsulin S. C-Peptide
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