Test Catalog

Test Id : PINS

Proinsulin, Plasma

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Method Name
A short description of the method used to perform the test

Electrochemiluminescent Assay

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.


Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Proinsulin, P

Specimen Type
Describes the specimen type validated for testing

Plasma EDTA

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation:

1.Patient should be fasting for 8 hours.

2. Infants younger than 2 years of age should fast a maximum of 6 hours.

Supplies: Sarstedt 5 mL Aliquot Tube (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 plastic vial and send frozen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.25 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Plasma EDTA Frozen 30 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 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. 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.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

3.6-22 pmol/L

Provides information to assist in interpretation of the test results

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 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, obesity.

Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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 II diabetes mellitus can have increased proinsulin, C-peptide, and insulin values, but usually without suppressed (<45 mg/dL) blood glucose.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Murtha TD, Lupsa BC, Majumdar S, et al: A systematic review of proinsulin-secreting pancreatic neuroendocrine tumors. J Gastrointest Surg. 2017 Aug;21(8):1335-1341

2. Placzkowski KA, Vella A, Thompson GB, et al: Secular trends in the presentation and management of functioning insulinoma at the Mayo Clinic, 1987-2007. J Clin Endocrinol Metab. 2009 Apr;94(4):1069-1073

3. Vezzosi D, Bennet A., Fauvel J, Caron P: Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycemia related to endogenous hyperinsulinism. Eur J Endocrinol. 2007 Jul;157(1):75-83

4. Service FJ: Hypoglycemic disorders. N Engl J Med. 1995 Apr;322(17):1144-1152

5. Steiner DF: The proprotein convertases. Curr Opin Chem Biol. 1998 Feb;2(1):31-39

Method Description
Describes how the test is performed and provides a method-specific reference

Sequential 2-site electrochemiluminescent immunoassay performed on the MesoScale Discovery instrument. The assay uses a monoclonal biotinylated anti-insulin capture antibody and an anti-C-peptide detection antibody labeled with SULFO-TAG. The signal is directly proportional to the amount of proinsulin in the sample. Assay calibration is traceable to the WHO 1st International Standard for human proinsulin, NIBSC code: 09/296. This assay demonstrates no cross-reactivity with insulin or C-peptide.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information


Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Tuesday, Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test


Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.


LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PINS Proinsulin, P 27882-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
80908 Proinsulin, P 27882-0

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports