, Volume 10, Issue 2, pp 115–119 | Cite as

Growth hormone assays: current methodologies and their limitations



Measurement of circulating growth hormone (GH) concentrations is essential in diagnosis of either GH deficiency or GH excess. The invention of immunoassays for the measurement of peptide hormones was a major breakthrough, enabling the routine analysis of GH concentrations in larger series of samples. Over the last few decades, measurement technology has evolved from less sensitive, mainly radioactive assays based on polyclonal antisera to the latest generations of highly sensitive chemiluminescence methods employing monoclonal antibodies. Unfortunately, the development of newer assays did not lead to better agreement among the results obtained by different assay methods. On the contrary, the differences tended to increase when monoclonal antibody based assays became more popular. The actual value reported for the GH concentration in a specific patient’s sample still mainly depends on the method used by the respective laboratory, limiting the applicability of international consensus guidelines in clinical practice. The heterogeneity of the analyte itself, the availability of different reference preparations for calibration and the interference from matrix components such as GH binding protein are among the reasons why standardizing GH assays is difficult. An additional challenge arose from the availability of a GH receptor antagonist for the treatment of acromegaly, which is basically a mutated form of GH and therefore interferes in many GH assays. This review provides an overview on GH assays used in clinical practice, their limitations and the potential next steps towards standardization.


Immunoassay Polyclonal Monoclonal Antibody Isoform Binding protein 


  1. 1.
    Gemzell CA, Heijkenskjold F, Strom L (1955) A method for demonstrating growth hormone activity in human plasma. J Clin Endocrinol Metab 15:537–546PubMedGoogle Scholar
  2. 2.
    Segaloff A, Komrad EL, Flores A, Segaloff A, Hardesty M (1955) The growth hormone content of human plasma. Endocrinology 57:527–530PubMedGoogle Scholar
  3. 3.
    Yalow RS, Berson SA (1959) Assay of plasma insulin in human subjects by immunological methods. Nature 184(Suppl 21):1648–1649PubMedCrossRefGoogle Scholar
  4. 4.
    Ehrlich RM, Randle PJ (1961) Immunoassay of growth hormone in human serum. Lancet 2:230–233PubMedCrossRefGoogle Scholar
  5. 5.
    Schalch DS, Parker ML (1964) A sensitive double antibody immunoassay for human growth hormone in plasma. Nature 203:1141–1142PubMedCrossRefGoogle Scholar
  6. 6.
    Morris HG, Arai Y, Hlad CJ Jr, Tompkins R, Elrick H (1964) Rapid quantitative immunologic assay for human growth hormone. J Clin Endocrinol Metab 24:417–424PubMedGoogle Scholar
  7. 7.
    Orskov H, Thomsen HG, Yde H (1968) Wick chromatography for rapid and reliable immunoassay of insulin, glucagon and growth hormone. Nature 219:193–195PubMedCrossRefGoogle Scholar
  8. 8.
    van Weemen BK (2005) The rise of EIA/ELISA. Clin Chem 2226Google Scholar
  9. 9.
    Wu AH (2006) A selected history and future of immunoassay development and applications in clinical chemistry. Clin Chim Acta 369:119–124PubMedCrossRefGoogle Scholar
  10. 10.
    Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedCrossRefGoogle Scholar
  11. 11.
    Dattani MT, Hindmarsh PC, Brook CG, Robinson IC, Weir T, Marshall NJ (1993) Enhancement of growth hormone bioactivity by zinc in the eluted stain assay system. Endocrinology 133:2803–2808PubMedCrossRefGoogle Scholar
  12. 12.
    Lesniak MA, Gorden P, Roth J, Gavin JR III (1974) Binding of 125I-human growth hormone to specific receptors in human cultured lymphocytes. Characterization of the interaction and a sensitive radioreceptor assay. J Biol Chem 249:1661–1667PubMedGoogle Scholar
  13. 13.
    Chapman IM, Hartman ML, Straume M, Johnson ML, Veldhuis JD, Thorner MO (1994) Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower postglucose nadir GH concentrations in men than women. J Clin Endocrinol Metab 78:1312–1319PubMedCrossRefGoogle Scholar
  14. 14.
    Popii V, Baumann G (2004) Laboratory measurement of growth hormone. Clin Chim Acta 350:1–16PubMedCrossRefGoogle Scholar
  15. 15.
    Strasburger CJ, Bidlingmaier M (2005) How robust are laboratory measures of growth hormone status? Horm Res 64(Suppl 2):1–5PubMedCrossRefGoogle Scholar
  16. 16.
    Bidlingmaier F, Geilenkeuser WJ, Kruse R, Rohle G (1991) Our experience with quality control in current growth hormone assays. Horm Res 36(Suppl 1):1–4PubMedGoogle Scholar
  17. 17.
    Seth J, Ellis A, Al-Sadie R (1999) Serum growth hormone measurements in clinical practice: an audit of performance from the UK National External Quality Assessment scheme. Horm Res 51:13–19PubMedCrossRefGoogle Scholar
  18. 18.
    Morsky P, Tiikkainen U, Ruokonen A, Markkanen H (2005) Problematic determination of serum growth hormone: experience from external quality assurance surveys 1998–2003. Scand J Clin Lab Invest 65:377–386PubMedCrossRefGoogle Scholar
  19. 19.
    Tanaka T, Tachibana K, Shimatsu A, Katsumata N, Tsushima T, Hizuka N, Fujieda K, Yokoya S, Irie M (2005) A nationwide attempt to standardize growth hormone assays. Horm Res 64(Suppl 2):6–11PubMedCrossRefGoogle Scholar
  20. 20.
    Celniker AC, Chen AB, Wert RM Jr, Sherman BM (1989) Variability in the quantitation of circulating growth hormone using commercial immunoassays. J Clin Endocrinol Metab 68:469–476PubMedGoogle Scholar
  21. 21.
    Granada ML, Sanmarti A, Lucas A, Salinas I, Carrascosa A, Foz M, Audi L (1990) Assay-dependent results of immunoassayable spontaneous 24-hour growth hormone secretion in short children. Acta Paediatr Scand Suppl 370:63–70; discussion 71PubMedGoogle Scholar
  22. 22.
    Markkanen H, Pekkarinen T, Valimaki MJ, Alfthan H, Kauppinen-Makelin R, Sane T, Stenman UH (2006) Effect of sex and assay method on serum concentrations of growth hormone in patients with acromegaly and in healthy controls. Clin Chem 52:468–473PubMedCrossRefGoogle Scholar
  23. 23.
    Hauffa BP, Lehmann N, Bettendorf M, Mehls O, Dorr HG, Partsch CJ, Schwarz HP, Stahnke N, Steinkamp H, Said E, Sander S, Ranke MB (2004) Central reassessment of GH concentrations measured at local treatment centers in children with impaired growth: consequences for patient management. Eur J Endocrinol 150:291–297PubMedCrossRefGoogle Scholar
  24. 24.
    Juul A, Bernasconi S, Clayton PE, Kiess W, DeMuinck-Keizer Schrama S (2002) European audit of current practice in diagnosis and treatment of childhood growth hormone deficiency. Horm Res 58:233–241PubMedCrossRefGoogle Scholar
  25. 25.
    Wieringa GE, Barth JH, Trainer PJ (2004) Growth hormone assay standardization: a biased view? Clin Endocrinol (Oxf) 60:538–539CrossRefGoogle Scholar
  26. 26.
    Trainer PJ, Barth J, Sturgeon C, Wieringa G (2006) Consensus statement on the standardisation of GH assays. Eur J Endocrinol 155:1–2PubMedCrossRefGoogle Scholar
  27. 27.
    Sheppard MC (2007) Growth hormone assay standardization: an important clinical advance. Clin Endocrinol (Oxf) 66:157–161CrossRefGoogle Scholar
  28. 28.
    Ekins R (1991) Immunoassay standardization. Scand J Clin Lab Invest Suppl 205:33–46PubMedGoogle Scholar
  29. 29.
    Baumann G (1991) Growth hormone heterogeneity: genes, isohormones, variants, and binding proteins. Endocr Rev 12:424–449PubMedCrossRefGoogle Scholar
  30. 30.
    Baumann G (1999) Growth hormone heterogeneity in human pituitary and plasma. Horm Res 51:2–6PubMedCrossRefGoogle Scholar
  31. 31.
    Baumann G, Stolar MW, Buchanan TA (1986) The metabolic clearance, distribution, and degradation of dimeric and monomeric growth hormone (GH): implications for the pattern of circulating GH forms. Endocrinology 119:1497–1501PubMedGoogle Scholar
  32. 32.
    Chatelain P, Bouillat B, Cohen R, Sassolas G, Souberbielle JC, Ruitton A, Joly MO, Job JC (1990) Assay of growth hormone levels in human plasma using commercial kits: analysis of some factors influencing the results. Acta Paediatr Scand Suppl 370:56–61; discussion 62PubMedGoogle Scholar
  33. 33.
    Reiter EO, Morris AH, MacGillivray MH, Weber D (1988) Variable estimates of serum growth hormone concentrations by different radioassay systems. J Clin Endocrinol Metab 66:68–71PubMedGoogle Scholar
  34. 34.
    Hayakawa M, Shimazaki Y, Tsushima T, Kato Y, Takano K, Chihara K, Shimatsu A, Irie M (2004) Metabolic effects of 20-kilodalton human growth hormone (20K-hGH) for adults with growth hormone deficiency: results of an exploratory uncontrolled multicenter clinical trial of 20K-hGH. J Clin Endocrinol Metab 89:1562–1571PubMedCrossRefGoogle Scholar
  35. 35.
    Baumann G (2001) Growth hormone binding protein 2001. J Pediatr Endocrinol Metab 14:355–375PubMedGoogle Scholar
  36. 36.
    Amit T, Youdim MB, Hochberg Z (2000) Clinical review 112: does serum growth hormone (GH) binding protein reflect human GH receptor function? J Clin Endocrinol Metab 85:927–932PubMedCrossRefGoogle Scholar
  37. 37.
    Jan T, Shaw MA, Baumann G (1991) Effects of growth hormone-binding proteins on serum growth hormone measurements. J Clin Endocrinol Metab 72:387–391PubMedCrossRefGoogle Scholar
  38. 38.
    Ebdrup L, Fisker S, Sorensen HH, Ranke MB, Orskov H (1999) Variety in growth hormone determinations due to use of different immunoassays and to the interference of growth hormone-binding protein. Horm Res 51:20–26PubMedCrossRefGoogle Scholar
  39. 39.
    Jansson C, Boguszewski C, Rosberg S, Carlsson L, Albertsson-Wikland K (1997) Growth hormone (GH) assays: influence of standard preparations, GH isoforms, assay characteristics, and GH-binding protein. Clin Chem 43:950–956PubMedGoogle Scholar
  40. 40.
    Hansen TK, Fisker S, Hansen B, Sorensen HH, Christiansen JS, Jorgensen JO, Orskov H (2002) Impact of GHBP interference on estimates of GH and GH pharmacokinetics. Clin Endocrinol (Oxf) 57:779–786CrossRefGoogle Scholar
  41. 41.
    Tsushima T, Katoh Y, Miyachi Y, Chihara K, Teramoto A, Irie M, Hashimoto Y (1999) Serum concentration of 20K human growth hormone (20K hGH) measured by a specific enzyme-linked immunosorbent assay. Study Group of 20K hGH. J-Clin-Endocrinol-Metab 84:317–322 issn: 0021-972xPubMedCrossRefGoogle Scholar
  42. 42.
    Wu Z, Bidlingmaier M, Dall R, Strasburger CJ (1999) Detection of doping with human growth hormone. LANCET Lancet 353:895Google Scholar
  43. 43.
    Boguszewski CL, Boguszewski MC, de Zegher F, Carlsson B, Carlsson LM (2000) Growth hormone isoforms in newborns and postpartum women. Eur J Endocrinol 142:353–358PubMedCrossRefGoogle Scholar
  44. 44.
    Strasburger CJ, Wu Z, Pflaum CD, Dressendorfer RA (1996) Immunofunctional assay of human growth hormone (hGH) in serum: a possible consensus for quantitative hGH measurement. J Clin Endocrinol Metab 81:2613–2620PubMedCrossRefGoogle Scholar
  45. 45.
    Strasburger C, Barnard G, Toldo L, Zarmi B, Zadik Z, Kowarski A, Kohen F (1989) Somatotropin as measured by a two-site time-resolved immunofluorometric assay [see comments]. Clin Chem 35:913–917PubMedGoogle Scholar
  46. 46.
    Stenman UH (2001) Immunoassay standardization: is it possible, who is responsible, who is capable? Clin Chem 47:815–820PubMedGoogle Scholar
  47. 47.
    Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML, Stephens PA (2006) Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 91:1621–1634PubMedCrossRefGoogle Scholar
  48. 48.
    Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, Ghigo E, Ho K, Jaquet P, Kleinberg D, Lamberts S, Laws E, Lombardi G, Sheppard MC, Thorner M, Vance ML, Wass JA, Giustina A (2005) Consensus statement: medical management of acromegaly. Eur J Endocrinol 153:737–740PubMedCrossRefGoogle Scholar
  49. 49.
    GH Research Society (2000) Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab 85:3990–3993CrossRefGoogle Scholar
  50. 50.
    Growth Hormone Research Society Workshop (1998) Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab 83:379–381CrossRefGoogle Scholar
  51. 51.
    Freda PU, Nuruzzaman AT, Reyes CM, Sundeen RE, Post KD (2004) Significance of “abnormal” nadir growth hormone levels after oral glucose in postoperative patients with acromegaly in remission with normal insulin-like growth factor-I levels. J Clin Endocrinol Metab 89:495–500PubMedCrossRefGoogle Scholar
  52. 52.
    Freda PU, Post KD, Powell JS, Wardlaw SL (1998) Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 83:3808–3816PubMedCrossRefGoogle Scholar
  53. 53.
    Bristow A, Berger P, Bidart JM, Birken S, Norman R, Stenman UH, Sturgeon C (2005) Establishment, value assignment, and characterization of new WHO reference reagents for six molecular forms of human chorionic gonadotropin. Clin Chem 51:177–182PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Martin Bidlingmaier
    • 1
  • Christian J. Strasburger
    • 2
  1. 1.Endocrine Research Laboratories, Medizinische Klinik—Innenstadt, Ludwig-Maximilians UniversityMunichGermany
  2. 2.Division of Clinical EndocrinologyCharité Campus MitteBerlinGermany

Personalised recommendations