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23352 Proinsulin, Plasma (PINS)

Proinsulin, Plasma (PINS)
Test Code: PROINSO
Synonyms/Keywords
Proinsulin, P
Useful For
As part of the diagnostic workup of suspected insulinoma
 
As part of the diagnostic workup of patients with suspected prohormone convertases1/3 deficiency
 
As part of the diagnostic workup of patients with suspected proinsulin variations
Specimen Requirements
Fasting Required Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Yes​ ​Plasma EDTA ​Ice-cooled, EDTA Lavender Top Tube (LTT) ​0.5 mL ​0.25 mL
Collection Processing Instructions
Patient should be fasting for 8 hours. Infants under 2 years of age should fast a maximum of 6 hours. After draw, chill the whole blood on ice for at least 10 minutes, then spin down in a refrigerated centrifuge.  Send specimen in plastic vial.
Specimen Stability Information
Specimen Type Temperature Time
​Plasma EDTA ​Frozen  30 days
Rejection Criteria
Hemolysis Gross
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Mayo Clinic Laboratories Varies ​1 day
Electrochemiluminescent Assay​
Reference Lab
Test Information
Proinsulin is the precursor of insulin and C-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 of insulinoma rests primarily on demonstrating non-suppressed 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. The use of hypoglycemic drugs (eg, sulfonylurea) or insulin injections can also mimic insulinoma. Diagnostic evaluations frequently require 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 over-secretion of insulin by insulinomas causes release of increased numbers of immature secretory granules with incompletely processed proinsulin, resulting in elevated serum/plasma proinsulin concentrations. This relative over-secretion of proinsulin insulinomas tends to be most marked in the fasting state, when proinsulin normally does not account for more than 5% of insulin concentrations on a molar basis.
 
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. Mutations in the proinsulin molecule have been reported that affect PC cleavage efficiency or subsequent proinsulin metabolism. These mutations can also lead to markedly elevated proinsulin levels, but are usually not accompanied by diabetes, or any other hormonal abnormalities.
Reference Range Information
Performing Location Reference Range
​Mayo Clinic Laboratories 3.6-22 pmol/L
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, and this is the cutoff recommended by the Mayo Clinic's highly experienced hypoglycemia team to avoid missing cases. However, the lower cutoff results in a reduced specificity (approximately 40%), emphasizing the need for a combination of different tests to assure accurate biochemical diagnosis.
 
Patients with PC1/3 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, morbid obesity.
 
This assay demonstrates no cross-reactivity with insulin or C-peptide.
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​84206
Synonyms/Keywords
Proinsulin, P
Ordering Applications
Ordering Application Description
​Centricity ​Proinsulin, P (80908)
​Cerner ​Proinsulin, P (80908)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Fasting Required Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Yes​ ​Plasma EDTA ​Ice-cooled, EDTA Lavender Top Tube (LTT) ​0.5 mL ​0.25 mL
Collection Processing
Patient should be fasting for 8 hours. Infants under 2 years of age should fast a maximum of 6 hours. After draw, chill the whole blood on ice for at least 10 minutes, then spin down in a refrigerated centrifuge.  Send specimen in plastic vial.
Specimen Stability Information
Specimen Type Temperature Time
​Plasma EDTA ​Frozen  30 days
Rejection Criteria
Hemolysis Gross
Useful For
As part of the diagnostic workup of suspected insulinoma
 
As part of the diagnostic workup of patients with suspected prohormone convertases1/3 deficiency
 
As part of the diagnostic workup of patients with suspected proinsulin variations
Reference Range Information
Performing Location Reference Range
​Mayo Clinic Laboratories 3.6-22 pmol/L
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, and this is the cutoff recommended by the Mayo Clinic's highly experienced hypoglycemia team to avoid missing cases. However, the lower cutoff results in a reduced specificity (approximately 40%), emphasizing the need for a combination of different tests to assure accurate biochemical diagnosis.
 
Patients with PC1/3 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, morbid obesity.
 
This assay demonstrates no cross-reactivity with insulin or C-peptide.
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Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
​Mayo Clinic Laboratories Varies ​1 day
Electrochemiluminescent Assay​
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​84206
For most current information refer to the Marshfield Laboratory online reference manual.