Discordance between mass spectrometry and immunometric IGF-1 assay in pituitary disease: a prospective study
- 104 Downloads
Measuring IGF-1, a biomarker for GH activity, is critical to evaluating disordered hypothalamic-pituitary GH axis. Inconsistent IGF-1 measurements among different immunoassays are well documented. We switched from Immulite 2000 immunoassay to narrow-mass-extraction, high-resolution liquid chromatography mass-spectrometry (LC-MS) compliant with recent consensus recommendations on assay standardization. Comparability of these two assays in patients with pituitary disease in a clinical practice setting is not known. We sought to compare IGF-1 levels on Immulite 2000 and LC-MS in samples from naïve and treated patients with secretory and non-secretory pituitary masses.
We prospectively collected serum samples from 101 patients treated at the Cedars-Sinai Pituitary Center between February 2012 and March 2014. We intentionally recruited more patients with acromegaly or GH deficiency to ensure a clinically representative cohort. Samples were classified as in or out of the respective reference ranges. Bland–Altman analysis was used to assess agreement between assays.
Twenty-four percent of samples were classified differently as below, in, or above range. Agreement between the assays was poor overall, with a significant bias for immunoassay reporting higher values than LC-MS. This pattern was also observed in patients with acromegaly and those with ≥ 2 pituitary hormone deficiencies.
IGF-1 results may differ after switching from an older immunoassay to a consensus-compliant assay such as LC-MS. Clinicians should consider the potential impact of assay switching before altering treatment due to discrepant results, particularly in patients monitored over time, such as those with acromegaly and GH deficiency.
KeywordsInsulin-like growth factor Pituitary disease Mass spectrometry Immunoassay
The authors thank Dr. Michael P. Caulfield (Quest Diagnostics) for edits and manuscript discussion and Ms. Shira Berman (Cedars-Sinai Medical Center) for manuscript preparation.
Compliance with ethical standards
Conflict of interest
Vivien Bonert declares that she has no conflict of interest. John Carmichael declares that he has no conflict of interest. Zengru Wu is an employee of Quest Diagnostics, Inc. James Mirocha declares that he has no conflict of interest. Daniel Perez declares that he has no conflict of interest. Nigel Clarke is an employee of Quest Diagnostics, Inc. Richard Reitz is an employee of Quest Diagnostics, Inc. Michael McPhaul is an employee of Quest Diagnostics, Inc. Adam Mamelak declares that he has no conflict of interest.
- 5.Brabant G, von zur Muhlen A, Wuster C, Ranke MB, Kratzsch J, Kiess W, Ketelslegers JM, Wilhelmsen L, Hulthen L, Saller B, Mattsson A, Wilde J, Schemer R, Kann P (2003) Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res 60(2):53–60PubMedGoogle Scholar
- 10.Bidlingmaier M, Friedrich N, Emeny RT, Spranger J, Wolthers OD, Roswall J, Korner A, Obermayer-Pietsch B, Hubener C, Dahlgren J, Frystyk J, Pfeiffer AF, Doering A, Bielohuby M, Wallaschofski H, Arafat AM (2014) Reference intervals for insulin-like growth factor-1 (IGF-I) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations. J Clin Endocrinol Metab 99(5):1712–1721. https://doi.org/10.1210/jc.2013-3059 CrossRefPubMedGoogle Scholar
- 11.Chanson P, Arnoux A, Mavromati M, Brailly-Tabard S, Massart C, Young J, Piketty ML, Souberbielle JC, Investigators V (2016) Reference values for IGF-I serum concentrations: comparison of six immunoassays. J Clin Endocrinol Metab 101(9):3450–3458. https://doi.org/10.1210/jc.2016-1257 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Burns C, Rigsby P, Moore M, Rafferty B (2009) The first international standard for insulin-like growth factor-1 (IGF-1) for immunoassay: preparation and calibration in an international collaborative study. Growth Horm IGF Res 19(5):457–462. https://doi.org/10.1016/j.ghir.2009.02.002 CrossRefPubMedGoogle Scholar
- 13.Kay R, Halsall DJ, Annamalai AK, Kandasamy N, Taylor K, Fenwick S, Webb A, Wark G, Pleasance S, Gurnell M (2013) A novel mass spectrometry-based method for determining insulin-like growth factor 1: assessment in a cohort of subjects with newly diagnosed acromegaly. Clin Endocrinol (Oxf) 78(3):424–430. https://doi.org/10.1111/cen.12085 CrossRefGoogle Scholar
- 17.Cox HD, Lopes F, Woldemariam GA, Becker JO, Parkin MC, Thomas A, Butch AW, Cowan DA, Thevis M, Bowers LD, Hoofnagle AN (2014) Interlaboratory agreement of insulin-like growth factor 1 concentrations measured by mass spectrometry. Clin Chem 60(3):541–548. https://doi.org/10.1373/clinchem.2013.208538 CrossRefPubMedGoogle Scholar
- 20.IMMULITE® (2005) 2000 IGF-I [package insert]. In: Diagnostic products corporation. IMMULITE®, Los AngelesGoogle Scholar
- 25.Granada ML, Ulied A, Casanueva FF, Pico A, Lucas T, Torres E, Sanmarti A (2008) Serum IGF-I measured by four different immunoassays in patients with adult GH deficiency or acromegaly and in a control population. Clin Endocrinol (Oxf) 68(6):942–950. https://doi.org/10.1111/j.1365-2265.2007.03120.x CrossRefGoogle Scholar
- 26.Krebs A, Wallaschofski H, Spilcke-Liss E, Kohlmann T, Brabant G, Volzke H, Nauck M (2008) Five commercially available insulin-like growth factor I (IGF-I) assays in comparison to the former Nichols Advantage IGF-I in a growth hormone treated population. Clin Chem Lab Med 46(12):1776–1783. https://doi.org/10.1515/CCLM.2008.349 CrossRefPubMedGoogle Scholar
- 27.Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A, van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KK, Casanueva FF, Melmed S (2014) Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10(4):243–248. https://doi.org/10.1038/nrendo.2014.21 CrossRefPubMedGoogle Scholar
- 28.Yuen KC, Tritos NA, Samson SL, Hoffman AR, Katznelson L (2016) American association of clinical endocrinologists and american college of endocrinology disease state clinical review: update on growth hormone stimulation testing and proposed revised cut-point for the glucagon stimulation test in the diagnosis of adult growth hormone deficiency. Endocr Pract 22(10):1235–1244. https://doi.org/10.4158/EP161407.DSCR CrossRefPubMedGoogle Scholar
- 29.Hines J, Milosevic D, Ketha H, Taylor R, Algeciras-Schimnich A, Grebe SK, Singh RJ (2015) Detection of IGF-1 protein variants by use of LC-MS with high-resolution accurate mass in routine clinical analysis. Clin Chem 61(7):990–991. https://doi.org/10.1373/clinchem.2014.234799 CrossRefPubMedGoogle Scholar
- 30.Wu Z, Sanders HR, Clarke NJ, Caulfield MP, Reitz RE, McPhaul MJ (2016) Identification of circulating IGF-1 polymorphisms by high resolution LC-MS. In: 98th Annual Meeting of the Endocrine Society, Boston, Massachusetts, April 1–4, p. Poster SAT 017Google Scholar
- 32.Varewijck AJ, Lamberts SW, van der Lely AJ, Neggers SJ, Hofland LJ, Janssen JA (2015) The introduction of the IDS-iSYS total IGF-1 assay may have far-reaching consequences for diagnosis and treatment of GH deficiency. J Clin Endocrinol Metab 100(1):309–316. https://doi.org/10.1210/jc.2014-2558 CrossRefPubMedGoogle Scholar
- 34.Yuen KC, Cook DM, Sahasranam P, Patel P, Ghods DE, Shahinian HK, Friedman TC (2008) Prevalence of GH and other anterior pituitary hormone deficiencies in adults with nonsecreting pituitary microadenomas and normal serum IGF-1 levels. Clin Endocrinol (Oxf) 69(2):292–298. https://doi.org/10.1111/j.1365-2265.2008.03201.x CrossRefGoogle Scholar