eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Hyperinsulinemia: Differential Diagnoses & Workup
Updated: Jul 9, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Beckwith-Wiedemann Syndrome
Infant of Diabetic Mother
Panhypopituitarism
Other Problems to Be Considered
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 µU/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
Workup
Laboratory Studies
All patients suspected of having hyperinsulinism should have blood obtained for measurement of concentrations of glucose, insulin, growth hormone, cortisol, free fatty acids, and beta-hydroxybutyrate. ABG measurement and assessment of lactate, pyruvate, and alanine levels are also helpful. These studies should be performed while the patient is hypoglycemic. Because most patients in a metabolic crisis present to a general practitioner rather than to a pediatric endocrinologist, the undiagnosed patient is bemused when the practitioner obtains serum during the crisis. The practitioner should obtain 5-10 mL of whole blood in a plain red-top tube (without heparin) and instruct the laboratory to centrifuge the specimen to separate the serum for storage at -20°C within an hour of collection. This precious frozen serum from the time of the critical event can then be analyzed appropriately after consultation with the subspecialist.
A plasma insulin level higher than 2 µU/mL and a serum glucose concentration less than 60 mg/dL is diagnostic of hyperinsulinism. Infants with hyperinsulinism require unusually high rates of glucose infusion (>12 mg/kg/min compared with the physiologic rate of 6-8 mg/kg/min) to maintain glucose levels higher than 60 mg/dL. A glucose-to-insulin ratio below 3 and low concentrations of free fatty acids and ketones during hypoglycemia are highly suggestive of hyperinsulinism.
Low levels of beta-hydroxybutyrate (<1 µmol/L) in conjunction with low levels of free fatty acids (<1 µmol/L) during hypoglycemia may indicate hyperinsulinism.
Finding low levels (<120 ng/mL) of insulin-like growth factor binding protein-1 (IGFBP-1) may be useful. Insulin suppresses secretion of IGFBP-1, which normally is elevated in the fasting or hypoglycemic child, unless hyperinsulinism is present and suppresses hepatic IGFBP-1 release.
C-peptide levels should be elevated proportionately elevated with insulin levels. A low C-peptide level with a high insulin level may indicate surreptitious insulin administration.
If ingestion of oral hypoglycemic medications is suspected, a drug screen may be beneficial.
Imaging Studies
Imaging studies (eg, pancreatic ultrasonography, CT scan, MRI) are generally not very useful. However, pancreatic angiography and pancreatic venous sampling have successfully been used in selective cases to identify and localize focal causes of hyperinsulinism. Also, spiral CT scanning has been used for the localization of islet cell adenomas in adults.
Other Tests
A normal blood glucose level is above 60 mg/dL at every age. In the normal child, glycogen stores are depleted by fasting in order to maintain euglycemia. Thus, glycogen is normally depleted before the onset of hypoglycemia. Such a child responds to exogenous dextrose but not to exogenous glucagon.
A glycemic response is defined as when the circulating glucose level rises (>30 mg/dL above the basal level) immediately after administration of 1 mg of glucagon (intramuscular or intravenous). Such a glycemic response to glucagon in the face of hypoglycemia (blood glucose level <60 mg/dL) indicates inappropriately conserved glycogen stores. A glycemic response to glucagon is usually observed in hypoglycemic patients with hyperinsulinism.
L-leucine stimulates the secretion of insulin. Leucine-sensitive hypoglycemia is no longer considered to be a separate diagnostic entity. Determination of insulin concentration in response to leucine administration has been used as a test for hyperinsulinemia. This research test has no diagnostic value and can result in severe hypoglycemia.
Because pancreatic adenomas are often very small and have the same density as the normal pancreas, radiographic studies such as ultrasound, CT scan, and MRI are often of limited value. Pancreatic arteriography is invasive but has been useful in delineating an adenoma, even in infants and young children. Transhepatic pancreatic selective venous sampling also has been used to elucidate the extent of pancreatic involvement. Open pancreatic ultrasonography at the time of surgery may be helpful in locating a pancreatic insulin-secreting adenoma. More recently, positron emission tomography (PET) scanning has been effective in identifying such lesions.2,10
Procedures
Perioperative pancreatic catheterization may provide vital information for determining the extent of surgery.
Histologic Findings
Histologic examination of pancreatic tissue samples (frozen section) may also provide vital information for determining the extent of surgery. Histologic examination may reveal focal islet cell disease (potentially cured by partial pancreatectomy) or diffuse disease (which indicates the need for near-total pancreatectomy).
More on Hyperinsulinemia |
| Overview: Hyperinsulinemia |
 Differential Diagnoses & Workup: Hyperinsulinemia |
| Treatment & Medication: Hyperinsulinemia |
| Follow-up: Hyperinsulinemia |
| Multimedia: Hyperinsulinemia |
| References |
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References
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Further Reading
Keywords
hyperinsulinemia, beta-cell hyperplasia, hyperinsulinemic hypoglycemia, nesidioblastosis, neonatal hyperglycemia, primary hyperinsulinemia, hypoglycemia in children, hypoglycemia in infants, hyperinsulinism, growth hormone deficiency, hypocortisolemia, maternal diabetes, birth asphyxia, macrosomia, Beckwith-Wiedemann syndrome, omphalocele, macroglossia, visceromegaly, drug-induced hyperinsulinism, maternal toxemia, erythroblastosis fetalis, Munchausen syndrome by proxy, nesidioblastosis, islet adenomatosis, beta-cell adenoma, persistent hyperinsulinemic hypoglycemia of infancy, PHHI, leucine-sensitive hypoglycemia, islet cell dysmaturation syndrome
