Diagnostic Considerations
It is unusual for nondiabetic individuals who are not receiving glucose-lowering medications to have hypoglycemia. [13] It is recommended that the Whipple triad criteria be used to confirm and diagnose hypoglycemia before performing further diagnostic investigations. The Whipple triad includes the following [13] :
-
Low levels of plasma glucose
-
The presence of signs/symptoms associated with low plasma glucose
-
Symptomatic improvement of such signs/symptoms with rising plasma glucose levels
In healthy-appearing patients who have hypoglycemia, the differential diagnosis should include conditions that lead to endogenous hyperinsulinism (eg, insulinoma, accidental/factitious causes). [13] In ill-appearing patients with hypoglycemia, consider whether the cause could be medications, a critical illness, organ failure, hormone deficiencies, or non-islet cell tumors.
Patients with hyperinsulinism usually have elevated levels of insulin for their glucose concentration, meaning even if they do not have hypoglycemia, their insulin level is inappropriately high for their glucose levels (ie, plasma insulin level >2 µIU/mL when blood glucose level is < 60 mg/dL). In contrast, patients with the following disorders have an appropriate concentration of insulin for the simultaneous glucose concentration:
-
Adrenal insufficiency
-
Disorders of branched-chain amino acids
-
Enzymatic block in the Cori and alanine cycles
-
Fatty acid release/oxidation (ketone synthesis) disorders
-
Mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase deficiency
-
Ketone use disorders
-
Mitochondrial succinyl–coenzyme A transferase deficiency
-
Mitochondrial acetyl–coenzyme A acyltransferase deficiency
-
Fructosemia
-
Galactosemia
-
Glycerokinase deficiency
-
Glycogen-storage disease type Ia and type Ib (von Gierke disease, glucose-6-phosphatase deficiency)
-
Glycogen-storage disease type III (Cori disease; amylo-1, 6-glucosidase deficiency)
-
Glycogen-storage disease type VI (Hers disease, phosphorylase deficiency)
-
Growth hormone deficiency
Differential Diagnoses
-
Hyperinsulinism. Mechanisms of insulin secretion.
