Skip to main content

Advertisement

SpringerLink
Log in

IGF-I measurements in the diagnosis of adult growth hormone deficiency

  • Original Paper
  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Although serum insulin-like growth factor I (IGF-I) concentrations have utility as a screening test for growth hormone (GH) deficiency in children and young adults, they are less accurate for screening in adults over 40 years of age. There are two main limitations in the clinical use of IGF-I levels as a marker of GH secretion. First, IGF-I synthesis is not only regulated by GH but also by nutrient supply and by other hormones; second, low IGF-I levels in the presence of normal or increased GH secretion may reflect a peripheral resistance to GH action. Although serum IGF-I cannot be used as a stand-alone test for the diagnosis of adult GH deficiency, very low IGF-I levels in the context of documented hypothalamic or pituitary disease may be helpful in identifying patients with a high probability of GH deficiency. In the presence of two or more additional pituitary hormone deficiencies, an IGF-I level <84 μg/l (assayed by Esoterix Endocrinology, Inc. Calabasas Hills, CA, USA) indicates a 99% probability of GH deficiency. As this cut-off value has not been validated for other IGF-I assays, an IGF-I standard deviation score (SDS) of <-3 may be considered in adults over age 28; an even lower IGF-I SDS is needed for diagnosis in younger adults. In clinical practice, other causes of low serum IGF-I such as malnutrition, diabetes, hypothyroidism, liver disease, etc., should be excluded before applying these diagnostic criteria.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Clemmons DR, Underwood LE (1991) Nutritional regulation of IGF-I and IGF binding proteins. Annu Rev Nutr 11:393–412

    Article  PubMed  CAS  Google Scholar 

  2. Isley WL, Underwood LE, Clemmons DR (1983) Dietary components that regulate serum somatomedin-C concentrations in humans. J Clin Invest 71:175–182

    PubMed  CAS  Google Scholar 

  3. Juul A (2003) Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Horm IGF Res 13:113–170

    Article  PubMed  CAS  Google Scholar 

  4. Larsson SC, Wolk K, Brismar K, Wolk A (2005) Association of diet with serum insulin-like growth factor I in middle-aged and elderly men. Am J Clin Nutr 81:1163–1167

    PubMed  CAS  Google Scholar 

  5. Hartman ML, Clayton PE, Johnson ML, Celniker A, Perlman AJ, Alberti KG, Thorner MO (1993) A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans. J Clin Invest 91:2453–2462

    PubMed  CAS  Google Scholar 

  6. Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP (1981) Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest 67:1361–1369

    PubMed  CAS  Google Scholar 

  7. Zadik Z, Chalew SA, McCarter RJ Jr, Meistas M, Kowarski AA (1985) The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 60:513–516

    PubMed  CAS  Google Scholar 

  8. Clemmons DR, Van Wyk JJ (1984) Factors controlling blood concentration of somatomedin C. Clin Endocrinol Metab 13:113–143

    Article  PubMed  CAS  Google Scholar 

  9. Juul A, Main K, Blum WF, Lindholm J, Ranke MB, Skakkebæk NE (1994) The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients. Clin Endocrinol (Oxf) 41:85–93

    CAS  Google Scholar 

  10. Pasquali R, Vicennati V, Gambineri A, Pagotto U (2001) Hormones and pathophysiology of obesity. Eat Weight Disord 6(Suppl 3):9–20

    PubMed  CAS  Google Scholar 

  11. Eden Engstrom B, Burman P, Holdstock C, Ohrvall M, Sundbom M, Karlsson FA (2006) Effects of gastric bypass on the GH/IGF-I axis in severe obesity—and a comparison with GH deficiency. Eur J Endocrinol 154:53–59

    Article  PubMed  CAS  Google Scholar 

  12. Clasey JL, Weltman A, Patrie J, Weltman JY, Pezzoli S, Bouchard C, Thorner MO, Hartman ML (2001) Abdominal visceral fat and fasting insulin are important predictors of 24-hour GH release independent of age, gender, and other physiological factors. J Clin Endocrinol Metab 86:3845–3852

    Article  PubMed  CAS  Google Scholar 

  13. Rasmussen MH, Frystyk J, Andersen T, Breum L, Christiansen JS, Hilsted J (1994) The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-I (IGF-I), IGF-binding protein-3, insulin, and growth hormone. Metabolism 43:315–319

    Article  PubMed  CAS  Google Scholar 

  14. Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebæk NE, Hilsted J (1995) Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab 80:1407–1415

    Article  PubMed  CAS  Google Scholar 

  15. Frystyk J, Vestbo E, Skjærbæk C, Mogensen CE, Ørskov H (1995) Free insulin-like growth factors in human obesity. Metabolism 44(10 Suppl 4):37–44

    Article  PubMed  CAS  Google Scholar 

  16. Frystyk J, Ledet T, Moller N, Flyvbjerg A, Ørskov H (2002) Cardiovascular disease and insulin-like growth factor I. Circulation 106:893–895

    Article  PubMed  Google Scholar 

  17. Clauson PG, Brismar K, Hall K, Linnarsson R, Grill V (1998) Insulin-like growth factor-I and insulin-like growth factor binding protein-1 in a representative population of type 2 diabetic patients in Sweden. Scand J Clin Lab Invest 58:353–360

    Article  PubMed  CAS  Google Scholar 

  18. Kratzsch J, Blum WF, Schenker E, Keller E (1995) Regulation of growth hormone (GH), insulin-like growth factor (IGF)I, IGF binding proteins-1, -2, -3 and GH binding protein during progression of liver cirrhosis. Exp Clin Endocrinol Diabetes 103:285–291

    PubMed  CAS  Google Scholar 

  19. Buzzelli G, Dattolo P, Pinzani M, Brocchi A, Romano S, Gentilini P (1993) Circulating growth hormone and insulin-like growth factor-I in nonalcoholic liver cirrhosis with or without superimposed hepatocarcinoma: evidence of an altered circadian rhythm. Am J Gastroenterol 88:1744–1748

    PubMed  CAS  Google Scholar 

  20. Iglesias P, Díez JJ, Fernández-Reyes MJ, Méndez J, Bajo MA, Aguilera A, Selgas R (2004) Growth hormone, IGF-I and its binding proteins (IGFBP-1 and -3) in adult uraemic patients undergoing peritoneal dialysis and haemodialysis. Clin Endocrinol (Oxf) 60:741–749

    Article  CAS  Google Scholar 

  21. Jørgensen JOL, Vahl N, Hansen TB, Skjærbæk C, Fisker S, Ørskov H, Hagen C, Christiansen JS (1998) Determinants of serum insulin-like growth factor I in growth hormone deficient adults as compared to healthy subjects. Clin Endocrinol (Oxf) 48:479–486

    Article  Google Scholar 

  22. Fisker S, Jørgensen JOL, Vahl N, Ørskov H, Christiansen JS (1999) Impact of gender and androgen status on IGF-I levels in normal and GH-deficient adults. Eur J Endocrinol 141:601–608

    Article  PubMed  CAS  Google Scholar 

  23. Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA (1997) Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 82:550–555

    Article  PubMed  CAS  Google Scholar 

  24. Jørgensen JOL, Christensen JJ, Vestergaard E, Fisker S, Ovesen P, Christiansen JS (2005) Sex steroids and the growth hormone/insulin-like growth factor-I axis in adults. Horm Res 64(Suppl 2):37–40

    Article  PubMed  CAS  Google Scholar 

  25. Lissett CA, Shalet SM (2003) The impact of dose and route of estrogen administration on the somatotropic axis in normal women. J Clin Endocrinol Metab 88:4668–4672

    Article  PubMed  CAS  Google Scholar 

  26. Wiesli P, Zwimpfer C, Zapf J, Schmid C (2006) Pregnancy-induced changes in insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) in patients with growth hormone (GH) deficiency and excess. Acta Obstet Gynecol Scand 85:900–905

    Article  PubMed  CAS  Google Scholar 

  27. Gleeson HK, Shalet SM (2005) GH responsiveness varies during the menstrual cycle. Eur J Endocrinol 153:775–779

    Article  PubMed  CAS  Google Scholar 

  28. Iglesias P, Bayón C, Méndez J, González Gancedo P, Grande C, Díez JJ (2001) Serum insulin-like growth factor type 1, insulin-like growth factor-binding protein-1, and insulin-like growth factor-binding protein-3 concentrations in patients with thyroid dysfunction. Thyroid 11:1043–1048

    Article  PubMed  CAS  Google Scholar 

  29. Miell JP, Taylor AM, Jones J, Holly JM, Gaillard RC, Pralong FP, Ross RJ, Blum WF (1993) The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers. J Endocrinol 136:525–533

    Article  PubMed  CAS  Google Scholar 

  30. Wolthers OD, Juul A, Hansen M, Muller J, Pedersen S (1995) The insulin-like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide. Acta Paediatr 84:393–397

    PubMed  CAS  Google Scholar 

  31. Wajchenberg BL, Liberman B, Gianella Neto D, Morozimato MY, Semer M, Bracco LO, Salgado LR, Knoepfelmacher M, Borges MH, Pinto AC, Kater CE, Lengyel AM (1996) Growth hormone axis in Cushing’s syndrome. Horm Res 45:99–107

    PubMed  CAS  Google Scholar 

  32. Magiakou MA, Mastorakos G, Gomez MT, Rose SR, Chrousos GP (1994) Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing’s disease before and after surgical cure. J Clin Endocrinol Metab 78:131–137

    Article  PubMed  CAS  Google Scholar 

  33. Dahn MS, Lange MP, Jacobs LA (1988) Insulinlike growth factor 1 production is inhibited in human sepsis. Arch Surg 123:1409–1414

    PubMed  CAS  Google Scholar 

  34. Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, Hinds CJ (1999) Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 341:785–792

    Article  PubMed  CAS  Google Scholar 

  35. Karamifar H, Karimi M, Amirhakimi G, Sharbatialaei M, De Sanctis V (2004) Reduced insulin growth factor I concentrations in iron-overloaded beta thalassaemic patients with normal growth hormone secretion and liver function. Pediatr Endocrinol Rev 2(Suppl 2):256–258

    PubMed  Google Scholar 

  36. Hwa V, Haeusler G, Pratt KL, Little BM, Frisch H, Koller D, Rosenfeld RG (2006) Total absence of functional acid labile subunit, resulting in severe insulin-like growth factor deficiency and moderate growth failure. J Clin Endocrinol Metab 91:1826–1831

    Article  PubMed  CAS  Google Scholar 

  37. Blum WF (2000) Insulin-like growth factors (IGF) and IGF-binding proteins: their use for diagnosis of growth hormone deficiency. In: Juul A, Jørgensen JOL (eds) Growth hormone in adults. Cambridge University Press, Cambridge, pp 54–86

    Google Scholar 

  38. Gharib H, Cook DM, Saenger PH, Bengtsson B-Ǻ, Feld S, Nippoldt TB, Rodbard HW, Seibel JA, Vance ML, Zimmerman D, Palumbo PJ, Bergman DA, Garber JR, Hamilton CR Jr, Petak SM, Rettinger HI, Service FJ, Shankar TP, Stoffer SS, Tourletot JB; American Association of Clinical Endocrinologists Growth Hormone Task Force (2003) American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children—2003 update. Endocr Pract 9:64–76

    PubMed  Google Scholar 

  39. Growth Hormone Research Society (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 83:379–381

    Article  Google Scholar 

  40. Zapf J, Walter H, Froesch ER (1981) Radioimmunological determination of insulin like growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia. J Clin Invest 68:1321–1330

    Article  PubMed  CAS  Google Scholar 

  41. Biller BM, Samuels MH, Zagar A, Cook DM, Arafah BM, Bonert V, Stavrou S, Kleinberg DL, Chipman JJ, Hartman ML (2002) Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 87:2067–2079

    Article  PubMed  CAS  Google Scholar 

  42. Granada ML, Murillo J, Lucas A, Salinas I, Llopis MA, Castells I, Foz M, Sanmarti A (2000) Diagnostic efficiency of serum IGF-I, IGF-binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population. Eur J Endocrinol 142:243–253

    Article  PubMed  CAS  Google Scholar 

  43. Reutens AT, Hoffman DM, Leung KC, Ho KK (1995) Evaluation and application of a highly sensitive assay for serum growth hormone (GH) in the study of adult GH deficiency. J Clin Endocrinol Metab 80:480–485

    Article  PubMed  CAS  Google Scholar 

  44. Molitch ME (2002) Diagnosis of GH deficiency in adults—how good do the criteria need to be? J Clin Endocrinol Metab 87:473–476

    Article  PubMed  CAS  Google Scholar 

  45. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML, The Endocrine Society’s Clinical Guidelines Subcommittee (2006) Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 91:1621–1634

    Article  PubMed  CAS  Google Scholar 

  46. Bonert VS, Elashoff JD, Barnett P, Melmed S (2004) Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: diagnostic caveat for adult GH deficiency. J Clin Endocrinol Metab 89:3397–3401

    Article  PubMed  CAS  Google Scholar 

  47. Klibanski A, Clemmons DR, Christiansen J, Underwood L (1999) Growth hormone replacement therapy for growth hormone deficiency in adults: the changing role of growth hormone therapy. Endocr Pract 5:88–96

    Google Scholar 

  48. Poehlman ET, Copeland KC (1990) Influence of physical activity on insulin-like growth factor-I in healthy younger and older men. J Clin Endocrinol Metab 71:1468–1473

    Article  PubMed  CAS  Google Scholar 

  49. Corpas E, Harman SM, Piñyero MA, Roberson R, Blackman MR (1992) Growth hormone (GH)-releasing hormone-(1–29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab 75:530–535

    Article  PubMed  CAS  Google Scholar 

  50. Rosenfeld RG, Wilson DM, Lee PD, Hintz RL (1986) Insulin-like growth factors I and II in evaluation of growth retardation. J Pediatr 109:428–433

    Article  PubMed  CAS  Google Scholar 

  51. Span JPT, Pieters GFFM, Sweep CGJ, Swinkels LMJW, Smals AGH (1999) Plasma IGF-I is a useful marker of growth hormone deficiency in adults. J Endocrinol Invest 22:446–450

    PubMed  CAS  Google Scholar 

  52. Lissett CA, Jonsson P, Monson JP, Shalet SM; KIMS International Board (2003) Determinants of IGF-I status in a large cohort of growth hormone-deficient (GHD) subjects: the role of timing of onset of GHD. Clin Endocrinol (Oxf) 59:773–778

    Article  CAS  Google Scholar 

  53. Janssen YJ, Frolich M, Roelfsema F (1997) A low starting dose of genotropin in growth hormone-deficient adults. J Clin Endocrinol Metab 82:129–135

    Article  PubMed  CAS  Google Scholar 

  54. Attanasio AF, Howell S, Bates PC, Frewer P, Chipman J, Blum WF, Shalet SM (2002) Body composition, IGF-I and IGFBP-3 concentrations as outcome measures in severely GH-deficient (GHD) patients after childhood GH treatment: a comparison with adult onset GHD patients. J Clin Endocrinol Metab 87:3368–3372

    Article  PubMed  CAS  Google Scholar 

  55. Clayton PE, Cuneo RC, Juul A, Monson JP, Shalet SM, Tauber M (2005) Consensus statement on the management of the GH-treated adolescent in the transition to adult care. Eur J Endocrinol 152:165–170

    Article  PubMed  CAS  Google Scholar 

  56. Baum HB, Biller BM, Katznelson L, Oppenheim DS, Clemmons DR, Cannistraro KB, Schoenfeld DA, Best SA, Klibanski A (1996) Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency compared with that in normal men—a clinical research center study. J Clin Endocrinol Metab 81:84–92

    Article  PubMed  CAS  Google Scholar 

  57. Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ, HypoCCS Advisory Board, US HypoCCS Study Group (2002) Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab 87:477–485

    Article  PubMed  CAS  Google Scholar 

  58. Thissen JP, Ketelslegers JM, Maiter D (1996) Use of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in the diagnosis of acromegaly and growth hormone deficiency in adults. Growth Regul 6:222–229

    PubMed  CAS  Google Scholar 

  59. Toogood AA, Beardwell CG, Shalet SM (1994) The severity of growth hormone deficiency in adults with pituitary disease is related to the degree of hypopituitarism. Clin Endocrinol (Oxf) 41:511–516

    CAS  Google Scholar 

  60. Sassolas G, Chazot FB, Jaquet P, Bachelot I, Chanson P, Rudelli CC, Tauber JP, Allannic H, Bringer J, Roudaut N, Rohmer V, Roger P, Latapie JL, Reville P, Leutenegger M (1999) GH deficiency in adults: an epidemiological approach. Eur J Endocrinol 141:595–600

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. US Medical Division, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 5015, Indianapolis, IN, 46285, USA

    Anita Y. M. Kwan & Mark L. Hartman

Authors
  1. Anita Y. M. Kwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark L. Hartman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark L. Hartman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kwan, A.Y.M., Hartman, M.L. IGF-I measurements in the diagnosis of adult growth hormone deficiency. Pituitary 10, 151–157 (2007). https://doi.org/10.1007/s11102-007-0028-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-007-0028-8

Keywords

Search

Navigation