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HelpEpic Test Code LAB1086 Proinsulin, Plasma
Additional Codes
MML Code: PINS
NY State Approved
YesPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Reporting Name
Proinsulin, PMethod Name
Electrochemiluminescent Assay
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Plasma EDTA | Frozen | 30 days |
Specimen Required
Patient Preparation:
1.Patient should fast for 8 hours before specimen collection.
2. Infants younger than 2 years should fast a maximum of 6 hours.
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube: Ice-cooled, lavender top (EDTA)
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL
Collection Instructions:
1. After collection, place the whole blood on ice for at least 10 minutes, then centrifuge at refrigerated temperature.
2. Aliquot plasma into a plastic vial and send frozen.
Specimen Type
Plasma EDTASpecimen Minimum Volume
0.25 mL
Reference Values
3.6-22 pmol/L
Report Available
2 to 5 daysDay(s) Performed
Tuesday, Friday
CPT Code Information
84206
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | OK |
| Gross icterus | OK |
Useful For
As part of the diagnostic workup of suspected insulinoma
As part of the diagnostic workup of patients with suspected prohormone convertase 1/3 deficiency
As part of the diagnostic workup of patients with suspected proinsulin variations
Clinical Information
Proinsulin is the precursor of insulin and C-peptide (connecting peptide). Following synthesis, proinsulin is packaged into secretory granules, where it is processed to C-peptide and insulin by prohormone convertases (PC1/3 and PC2) and carboxypeptidase E. Only 1% to 3% of proinsulin is secreted intact. However, because proinsulin has a longer half-life than insulin, circulating proinsulin concentrations are in the range of 5% to 30% of circulating insulin concentrations on a molar basis, with the higher relative proportions seen after meals and in patients with insulin resistance or early type 2 diabetes. Proinsulin can bind to the insulin receptor and exhibits 5% to 10% of the metabolic activity of insulin.
Proinsulin levels might be elevated in patients with insulin-producing islet cell tumors (insulinomas). These patients suffer from hypoglycemic attacks due to inappropriate secretion of insulin by the tumors. The biochemical diagnosis rests primarily on demonstrating nonsuppressed insulin levels in the presence of hypoglycemia (blood glucose <45 mg/dL). The diagnosis can be difficult, as tumors might be small or secrete insulin only episodically. Insulin injections or hypoglycemic drugs can also mimic insulinoma. Evaluation of these patients frequently requires a prolonged fast (72 hours) as well as supplementary tests in addition to insulin and glucose measurements, including a sulfonylurea screen and measurement of C-peptide, proinsulin, and beta-hydroxybutyrate. The inappropriate oversecretion of insulin by insulinomas causes the release of an increased numbers of secretory granules with incompletely processed insulin, resulting in elevated serum/plasma proinsulin concentrations. This oversecretion of proinsulin in insulinomas is accentuated during fasting, when proinsulin normally does not account for more than 5% of the insulin concentrations.
Proinsulin is strikingly elevated in PC1/3 deficiency. These patients have defects in the processing of multiple peptide hormones and suffer from diabetes, adrenal insufficiency, infertility, and obesity. Affected individuals typically have red hair regardless of racial background. Variants in the proinsulin molecule have been reported that affect PC cleavage efficiency or subsequent proinsulin metabolism. These variants can also lead to markedly elevated proinsulin levels but are usually not accompanied by diabetes or any other hormonal abnormalities.
Interpretation
Normal individuals will have proinsulin concentrations below the upper limit of the normal fasting reference range (22 pmol/L) when hypoglycemic (blood glucose <60 mg/dL). Conversely, most (>80%) insulinoma patients will have proinsulin concentrations above the upper limit of the reference range. The sensitivity and specificity for a diagnosis of insulinoma during hypoglycemia are approximately 75% and near 100%, respectively, at the 22 pmol/L cutoff. A higher sensitivity (>95%) can be achieved using a 5 pmol/L cutoff, which is recommended by Mayo Clinic's highly-experienced hypoglycemia team to avoid missing cases. However, the lower cutoff results in reduced specificity (approximately 40%), emphasizing the need for a combination of different tests to assure accurate biochemical diagnosis.
Patients with prohormone convertase 1/3 deficiency have low, or sometimes undetectable, insulin levels and substantially elevated proinsulin levels, exceeding the upper limit of the reference range substantially in the fasting state and rising even higher after food intake. Many other hormonal abnormalities are also present, including cortisol deficiency (because of lack of processing of pro-opiomelanocortin to adrenocorticotropic hormone and other peptides), infertility, and, often, obesity.
Cautions
To avoid misdiagnoses, all proinsulin measurements used in the diagnostic workup of patients with hypoglycemia must be interpreted in the context of coexisting illnesses, blood glucose concentration at the time of sampling, and other tests, namely, insulin, C-peptide, beta-hydroxybutyrate measurements, and a sulfonylurea drug screen.
Patients with chronic kidney failure and type 2 diabetes mellitus can have increased proinsulin, C-peptide, and insulin values but usually without suppressed (<45 mg/dL) blood glucose concentrations.