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PRLPM<br />

84462<br />

Clinical Information: Proinsulin is the precursor of insulin and C-peptide. Following synthesis,<br />

proinsulin is packaged into secretory granules, where it is processed to C-peptide and insulin by<br />

prohormone convertases (PC1/3 and PC2) and carboxypeptidase E. Only 1% to 3% of proinsulin is<br />

secreted intact. However, because proinsulin has a longer half-life than insulin, circulating proinsulin<br />

concentrations are in the range of 5% to 30% of circulating insulin concentrations on a molar basis, with<br />

the higher relative proportions seen after meals and in patients with insulin resistance or early type 2<br />

diabetes. Proinsulin can bind to the insulin receptor and exhibits 5% to 10% of the metabolic activity of<br />

insulin. Proinsulin levels might be elevated in patients with insulin-producing islet cell tumors<br />

(insulinomas). These patients suffer from hypoglycemic attacks due to inappropriate secretion of insulin<br />

by the tumors. The biochemical diagnosis of insulinoma rests primarily on demonstrating non-suppressed<br />

insulin levels in the presence of hypoglycemia (blood glucose 95%) can<br />

be achieved using a 5 pmol/L cutoff, and this is the cutoff recommended by the <strong>Mayo</strong> Clinic's highly<br />

experienced hypoglycemia team to avoid missing cases. However, the lower cutoff results in a reduced<br />

specificity (approximately 40%), emphasizing the need for a combination of different tests to assure<br />

accurate biochemical diagnosis. Patients with PC1/3 deficiency have low, or sometimes undetectable,<br />

insulin levels and substantially elevated proinsulin levels, exceeding the upper limit of the reference range<br />

substantially in the fasting state and rising even higher after food intake. Many other hormonal<br />

abnormalities are also present, including cortisol deficiency (because of lack of processing of<br />

pro-opiomelanocortin to adrenocorticotropic hormone and other peptides), infertility and, often, morbid<br />

obesity. This assay demonstrates no cross-reactivity with insulin or C-peptide.<br />

Reference Values:<br />

3-20 pmol/L<br />

Clinical References: 1. Kao PC, Taylor RL, Service FJ: Proinsulin by immunochemiluminometric<br />

assay for the diagnosis of insulinoma. J Clin Endocrinol Metab 1994;78(5):1048-1051 2. Service FJ:<br />

Hypoglycemic disorders. N Engl J Med 1995;322(17):1144-1152 3. Steiner DF: The proprotein<br />

convertases. Cur Opin Chem Biol 1998;2(1):31-39 4. Vezzosi D, Bennet A., Fauvel J, Caron P: Insulin,<br />

C-peptide and proinsulin for the biochemical diagnosis of hypoglycemia related to endogenous<br />

hyperinsulinism. Eur J Endocrinol 2007;157(1):75-83<br />

Prolactin, Pituitary Macroadenoma, Serum<br />

Clinical Information: Prolactin is secreted by the anterior pituitary gland. The major chemical<br />

Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or <strong>Mayo</strong><strong>Medical</strong><strong>Laboratories</strong>.com Page 1478

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