Abstract
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are the most important laboratory parameters used in the diagnosis of GH-related disorders in childhood and puberty. Problems of the immunoassays (IAs) for measuring GH and IGF-I, including lack of standardization, harmonization, and comparability, should be well understood and considered in the clinical assessment and interpretation. Application of liquid chromatography coupled to mass spectrometry (LC–MS) could overcome the limitations of IAs, but is still far from wide clinical use. One approach in diagnosing and management of GH deficiency relies solely on the measurement of IGF-I. The second, more traditional approach comprises a two-step testing of GH concentrations after pharmacologic stimulation. Abnormal concentration of steroids in children and adolescents is of great clinical importance for diagnosing a variety of disturbances, but modern IAs despite of their high capacity, speed, and automation do not meet the requirements for sensitivity and specificity and have unacceptable performance. LC–MS provides the highest possible reliability for steroid analysis and already becomes the preferred routine technique in many laboratories. Further significant advantages of LC–MS include relatively high throughput and the ability to perform panel steroid profiling with simultaneous measurement of precursors, active hormones, and metabolites in a single sample, thus amplifying enormously the informative value of laboratory results, with ultimate improvement of patient care.
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References
Winter WE, Bazydlo LAL, Harris NS. Quick guide to endocrinology. Washington, DC: AACC Press; 2013.
Winter WE, Jialal I, Vance ML, et al. Pituitary function and pathophysiology. In: Burtis CA, Ashwood ER, Bruns DE, editors. Tietz textbook of clinical chemistry and molecular diagnostics. St. Louis: Elsevier Saunders; 2012. p. 1803–45.
Boulo S, Hanisch K, Bidlingmaier M, et al. Gaps in the traceability chain of human growth hormone measurements. Clin Chem. 2013;59:1074–82.
Murray PG, Dattani MT, Clayton PE. Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence. Arch Dis Child. 2014. doi:10.1136/archdischild-2014-307228.
Van Helden J, Hermsen D, Von Ahsen N, et al. Performance evaluation of a fully automated immunoassay for the detection of human growth hormone on the Elecsys immunoassay system. Clin Lab. 2014;60:1641–51.
Wieringa GE, Sturgeon CM, Trainer PJ. The harmonisation of growth hormone measurements: taking the next steps. Clin Chim Acta. 2014;432:68–71.
Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem. 2011;57:555–9.
Gomez-Gomez C, Iglesias EM, Barallat J, et al. Lack of transferability between two automated immunoassays for serum IGF-I measurement. Clin Lab. 2014;60:1859–64.
Junnila RK, Strasburger CJ, Bidlingmaier M. Pitfalls of insulin-like growth factor-I and growth hormone assays. Endocrinol Metab Clin North Am. 2015;44:21–34.
Cox HD, Lopes F, Woldemariam GA, et al. Interlaboratory agreement of insulin-like growth factor 1. Concentrations measured by mass spectrometry. Clin Chem. 2014;60:541–8.
Such-Sanmartín G, Bache N, Bosch J, et al. Detection and differentiation of 22kDa and 20kDa growth hormone proteoforms in human plasma by LC-MS/MS. Biochim Biophys Acta. 1854;2015:284–90.
Oran PE, Trenchevska O, Nedelkov D, et al. Parallel workflow for high-throughput (>1,000 samples/day) quantitative analysis of human insulin-like growth factor 1 using mass spectrometric immunoassay. PLoS One. 2014;9:e92801.
Arsene CG, Henrion A, Diekmann N, et al. Quantification of growth hormone in serum by isotope dilution mass spectrometry. Anal Biochem. 2010;401:228–35.
Barton C, Kay RG, Gentzer W, et al. Development of high-throughput chemical extraction techniques and quantitative HPLC-MS/MS (SRM) assays for clinically relevant plasma proteins. J Proteome Res. 2010;9:333–40.
Wagner IV, Paetzold C, Gausche R, et al. Clinical evidence-based cutoff limits for GH stimulation tests in children with a backup of results with reference to mass spectrometry. Eur J Endocrinol. 2014;171:389–97.
Bidlingmaier M, Friedrich N, Emeny RT, et al. 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. 2014;99:1712–21.
Soldin S, Soldin OP. Steroid hormone analysis by tandem mass spectrometry. Clin Chem. 2009;55:1061–6.
Konforte D, Shea JL, Kyriakopoulou L, et al. Complex biological pattern of fertility hormones in children and adolescents: a study of healthy children from the CALIPER cohort and establishment of pediatric reference intervals. Clin Chem. 2013;59:1215–27.
Bertholf RL, Jialal I, Winter WE. The adrenal cortex. In: Burtis CA, Ashwood ER, Bruns DE, editors. Tietz textbook of clinical chemistry and molecular diagnostics. St. Louis: Elsevier Saunders; 2012. p. 1847–904.
Isbell TS, Jungheim E, Gronowski AM. Reproductive endocrinology and related disorders. In: Burtis CA, Ashwood ER, Bruns DE, editors. Tietz textbook of clinical chemistry and molecular diagnostics. St. Louis: Elsevier Saunders; 2012. p. 1945–90.
Turpeinen U, Hämäläinen E, Haanpää M, et al. Determination of salivary testosterone and androstenedione by liquid chromatography-tandem mass spectrometry. Clin Chim Acta. 2012;413:594–9.
Fritz KS, McKean AJS, Nelson JC, et al. Analog-based free testosterone test results linked to total testosterone concentrations, not free testosterone concentrations. Clin Chem. 2008;54:512–6.
Gröschl M. Current status of salivary hormone analysis. Clin Chem. 2008;54:1759–69.
Taylor A, Keevil B, Huhtaniemi IT. Mass spectrometry and immunoassay; how to measure steroid hormones today and tomorrow. Eur J Endocrinol. 2015;173:D1–12. European Society of Endocrinology, Manuscript EJE-15-0338.
Benton SC, Nuttal M, Nardo L, et al. Measured dehydroepiandrosterone sulfate positively influences testosterone measurement in unextracted female serum: comparison of 2 immunoassays with testosterone measured by LC-MS. Clin Chem. 2011;57:1174–83.
Huang X, Spink DC, Schneider E, et al. Measurement of unconjugated estriol in serum by liquid chromatography–tandem mass spectrometry and assessment of the accuracy of chemiluminescent immunoassays. Clin Chem. 2014;60:260–8.
Stanczyk FZ, Lee JS, Santen RJ. Standardization of steroid hormone assays: why, how, and when. Cancer Epidemiol Biomarkers Prev. 2007;16:1713–9.
Handelsman DJ, Newman JD, Jimenez M, et al. Performance of direct estradiol immunoassays with human male serum samples. Clin Chem. 2014;60:510–7.
Krone N, Hughes BA, Lavery GG. Gas chromatography/mass spectrometry (GC/MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/MS/MS). J Steroid Biochem Mol Biol. 2010;121:496–504.
Handelsman DJ, Wartofsky L. Requirement for mass spectrometry sex steroid assays in the Journal of Clinical Endocrinology and Metabolism. J Clin Endocrinol Metab. 2013;98:3971–3.
Kushnir MM, Rockwood AL, Roberts WL, et al. Liquid chromatography tandem mass spectrometry for analysis of steroids in clinical laboratories. Clin Biochem. 2011;44:77–88.
Ketha H, Kaur S, Grebe S, Sihgh RJ. Clinical applications of LC-MS sex steroid assays: evolution of methodologies in 21st century. Curr Opin Endocrinol Diabetes Obes. 2014;21:217–26.
Botelho JK, Shaklady C, Cooper HC, et al. Isotope-dilution liquid chromatography–tandem mass spectrometry candidate reference method for total testosterone in human serum. Clin Chem. 2013;59:372–80.
Rosner W. Another reference measurement procedure for total testosterone—what’s the fuss? Clin Chem. 2013;59:338–9.
Koal T, Schmiederer D, Pham-Tuan H, et al. Standardized LC-MS/MS based steroid hormone profile-analysis. J Steroid Biochem Mol Biol. 2012;129:129–38.
Shiraishi S, Lee PWN, Leund A, et al. Simultaneous measurement of serum testosterone and dihydrotestosterone by liquid chromatography–tandem mass spectrometry. Clin Chem. 2008;54:1855–63.
Kyriakopoulou L, Yazdanpanah M, Colantonio DA, et al. A sensitive and rapid mass spectrometric method for the simultaneous measurement of eight steroid hormones and CALIPER pediatric reference intervals. Clin Biochem. 2013;46:642–51.
Kushnir MM, Blamires T, Rockwood LA, et al. Liquid chromatography–tandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clin Chem. 2010;56:1138–47.
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Svinarov, D.A. (2016). Growth Hormone and Steroid Assays’ Problems in Childhood and Puberty. In: Kumanov, P., Agarwal, A. (eds) Puberty. Springer, Cham. https://doi.org/10.1007/978-3-319-32122-6_17
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DOI: https://doi.org/10.1007/978-3-319-32122-6_17
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