NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
As part of the diagnostic workup of suspected insulinoma
As part of the diagnostic workup of patients with suspected PC1/3 deficiency
As part of the diagnostic workup of patients with suspected proinsulin mutations
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Collection Container/Tube: Ice-cooled, lavender top (EDTA)
Submission Container/Tube: Plastic vial
Specimen Volume: 1.5 mL
2. After draw, chill the whole blood on ice for at least 10 minutes, then spin down in a refrigerated centrifuge.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross reject
Mild OK; Gross reject
Mild OK; Gross OK
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Plasma EDTA||Frozen (preferred)||14 days|
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. 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 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.
Normal individuals will have proinsulin concentrations below the upper limit of the normal fasting reference range (20 pmol/L) when hypoglycemic (blood glucose <45-60 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 20 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.
Cautions 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, the blood glucose concentration at the time of sampling, and other test results (ie, insulin, C-peptide, beta-hydroxybutyrate, and sulfonylurea drug screen). For example, patients with chronic renal failure or type 2 diabetes mellitus can have increased proinsulin, C-peptide and insulin values, but usually without suppressed (<45 g/dL) blood glucose.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Kao PC, Taylor RL, Service FJ: Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma. J Clin Endocrinol Metab 1994;78(5):1048-1051
2. Service FJ: Hypoglycemic disorders. N Engl J Med 1995;322(17):1144-1152
3. Steiner DF: The proprotein convertases. Cur Opin Chem Biol 1998;2(1):31-39
4. 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;157(1):75-83
Method Description Describes how the test is performed and provides a method-specific reference
A polyclonal capture antibody-conjugated bead recognizing human insulin is incubated with standards, controls and patient samples, capturing insulin and proinsulin, but not free C-peptide. Following washing, a polyclonal acridinium ester-labeled antiserum that recognizes C-peptide is added, binding to captured proinsulin, but not to captured insulin. After overnight incubation, the bead is washed, and flash-chemiluminescence is triggered and measured. The chemiluminescence signal is proportional to the concentration of proinsulin in the sample. (Kao PC, Taylor RT, Service FG: Proinsulin by novel ICMA-diagnostic implication for insulinoma. 75th Annual Meeting, Endocrine Society, #740, p 235, 1993; Kao PC, Taylor RT, Service FG: Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma. J Clin Endocrinol Metab 1994;78:1048-1051)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday, Thursday; 10 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|