Skip to main content
Log in

Diagnosis of adult GH deficiency

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Based on previous consensus statements, it has been widely accepted that the diagnosis of adult growth hormone deficiency (GHD) must be shown biochemically by provocative tests of GH secretion; in fact, the measurement of IGF-I as well as of other markers was considered unable to distinguish between normal and GHD subjects. The Insulin Tolerance Test (ITT) was indicated as that of choice and severe GHD defined by a GH peak lower than 3 μg/l. It is now recognized that, although normal IGF-I levels do not rule out severe GHD, very low IGF-I levels in patients highly suspected for GHD (i.e. patients with childhood-onset severe GHD or with multiple hypopituitarism acquired in adulthood) can be considered as definite evidence for severe GHD. However, patients suspected for adult GHD with normal IGF-I levels must be investigated by provocative tests. ITT remains a test of reference but it should be recognized that other tests are as reliable as ITT. Glucagon as classical test and, particularly, new maximal tests such as GHRH in combination with arginine or GH secretagogues (GHS) (i.e. GHRP-6) have well defined cut-off limits, are reproducible, able to distinguish between normal and GHD subjects. Overweight and obesity have confounding effect on the interpretation of the GH response to provocative tests. In adults cut-off levels of GH response below which severe GHD is demonstrated must be appropriate to lean, overweight and obese subjects to avoid false positive diagnosis in obese adults and false negative diagnosis in lean GHD patients.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Colao A (1999) The growth hormone (GH) response to the arginine plus GH-releasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency. J Clin Endocrinol Metab 84:1277–1282. doi:10.1210/jc.84.4.1277

    Article  PubMed  CAS  Google Scholar 

  2. Colao A (1999) Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 84:1919–1924. doi:10.1210/jc.84.6.1919

    Article  PubMed  CAS  Google Scholar 

  3. Colao A (2004) The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study. J Clin Endocrinol Metab 89:5998–6004. doi:10.1210/jc.2004-1042

    Article  PubMed  CAS  Google Scholar 

  4. Growth Hormone Research Society (1998) Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency. J Clin Endocrinol Metab 83:379–381. doi:10.1210/jc.83.2.379

    Article  Google Scholar 

  5. Molitch ME (2006) Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 91:1621–1634. doi:10.1210/jc.2005-2227

    Article  PubMed  CAS  Google Scholar 

  6. Aimaretti G (1998) Usefulness of IGF-I assay for the diagnosis of GH deficiency in adults. J Endocrinol Invest 21:506–511

    PubMed  CAS  Google Scholar 

  7. Ghigo E (2001) Growth hormone-releasing hormone combined with arginine or growth hormone secretagogues for the diagnosis of growth hormone deficiency in adults. Endocrine 15:29–38. doi:10.1385/ENDO:15:1:029

    Article  PubMed  CAS  Google Scholar 

  8. Gharib H (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 

  9. Aimaretti G (2003) Diagnostic reliability of a single IGF-I measurement in 237 adults with total anterior hypopituitarism and severe GH deficiency. Clin Endocrinol (Oxf) 59:56–61. doi:10.1046/j.1365-2265.2003.01794.x

    Article  CAS  Google Scholar 

  10. Hartman ML (2002) Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 87:477–485. doi:10.1210/jc.87.2.477

    Article  PubMed  CAS  Google Scholar 

  11. Attanasio AF (1997) Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. J Clin Endocrinol Metab 82:82–88. doi:10.1210/jc.82.1.82

    Article  PubMed  CAS  Google Scholar 

  12. Aimaretti G (2005) Different degrees of GH deficiency evidenced by GHRH-arginine test and IGF-I levels in adults with pituitary disease. J Endocrinol Invest 28:247–252

    PubMed  CAS  Google Scholar 

  13. Hilding A (1999) Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19–82 years, in relation to those in healthy subjects. J Clin Endocrinol Metab 84:2013–2019. doi:10.1210/jc.84.6.2013

    Article  PubMed  CAS  Google Scholar 

  14. Granada ML (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. doi:10.1530/eje.0.1420243

    Article  PubMed  CAS  Google Scholar 

  15. Boquete HR (2003) Evaluation of diagnostic accuracy of insulin-like growth factor IGF)-I and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis. J Clin Endocrinol Metab 88:4702–4708. doi:10.1210/jc.2003-030412

    Article  PubMed  CAS  Google Scholar 

  16. Ho KKY (2007) Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency II. Eur J Endocrinol 157:695–700

    Google Scholar 

  17. Jones SL (1994) An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year. Clin Endocrinol (Oxf) 41:123–128

    Article  CAS  Google Scholar 

  18. Hoeck HC (1995) Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test. Eur J Endocrinol 133:305–312

    Article  PubMed  CAS  Google Scholar 

  19. Vestergaard P (1997) Reproducibility of growth hormone and cortisol responses to the insulin tolerance test and the short ACTH test in normal adults. Horm Metab Res 29:106–110

    PubMed  CAS  Google Scholar 

  20. Ghigo E (2008) Diagnosis of adult GH deficiency. Growth Horm IGF Res 18:1–16

    Google Scholar 

  21. Aimaretti G (2000) Comparisons among old and new provocative tests of GH secretion in 178 normal adults. Eur J Endocrinol 142:347–352. doi:10.1530/eje.0.1420347

    Article  PubMed  CAS  Google Scholar 

  22. Biller BM (2002) Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 87:2067–2079. doi:10.1210/jc.87.5.2067

    Article  PubMed  CAS  Google Scholar 

  23. Hoffman DM (1994) Diagnosis of growth hormone deficiency in adults. Lancet 343:1064–1068. doi:10.1016/S0140-6736(94)90181-3

    Article  PubMed  CAS  Google Scholar 

  24. Ghigo E (1992) Arginine potentiates but does not restore the blunted growth hormone response to growth hormone-releasing hormone in obesity. Metabolism 41:560–563. doi:10.1016/0026-0495(92)90220-5

    Article  PubMed  CAS  Google Scholar 

  25. Procopio M (1995) Short-term fasting in obesity fails to restore the blunted GH responsiveness to GH-releasing hormone alone or combined with arginine. Clin Endocrinol (Oxf) 43:665–669

    Article  CAS  Google Scholar 

  26. Maccario M (1999) Assessment of GH/IGF-I axis in obesity by evaluation of IGF-I levels and the GH response to GHRH+arginine test. J Endocrinol Invest 22:424–429

    PubMed  CAS  Google Scholar 

  27. Maccario M (2001) Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency. Int J Obes Relat Metab Disord 25:1233–1239. doi:10.1038/sj.ijo.0801671

    Article  PubMed  CAS  Google Scholar 

  28. Cordido F (2003) Comparison between insulin tolerance test, growth hormone (GH)-releasing hormone (GHRH), GHRH plus acipimox and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese and hypopituitary patients. Eur J Endocrinol 149:117–122. doi:10.1530/eje.0.1490117

    Article  PubMed  CAS  Google Scholar 

  29. Bonert VS (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. doi:10.1210/jc.2003-032213

    Article  PubMed  CAS  Google Scholar 

  30. Qu XD (2005) Influence of body mass index and gender or growth hormone (GH) responses to GH-releasing hormone plus arginine and insulin tolerance tests. J Clin Endocrinol Metab 90:1563–1569. doi:10.1210/jc.2004-1450

    Article  PubMed  CAS  Google Scholar 

  31. Haijma SV (2005) The GHRH/GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men. Eur J Endocrinol 152:575–580. doi:10.1530/eje.1.01887

    Article  PubMed  CAS  Google Scholar 

  32. Kelestimur F (2006) Effect of obesity and morbid obesity on the growth hormone (GH) secretion elicited by the combined GHRH + GHRP-6 test. Clin Endocrinol (Oxf) 64:667–671. doi:10.1111/j.1365-2265.2006.02525.x

    Article  CAS  Google Scholar 

  33. Gomez JM (2002) Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf) 56:329–334. doi:10.1046/j.1365-2265.2002.01472.x

    Article  CAS  Google Scholar 

  34. Conceicao FL (2003) Glucagon stimulation test for the diagnosis of GH deficiency in adults. J Endocrinol Invest 26:1065–1070

    PubMed  CAS  Google Scholar 

  35. Aimaretti G (1998) Comparison between insulin-induced hypo-glycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. J Clin Endocrinol Metab 83:1615–1618. doi:10.1210/jc.83.5.1615

    Article  PubMed  CAS  Google Scholar 

  36. Aimaretti G (2000) Retesting young adults with childhood-onset growth hormone (GH) deficiency with GH-releasing-hormone-plus-arginine test. J Clin Endocrinol Metab 85:3693–3699. doi:10.1210/jc.85.10.3693

    Article  PubMed  CAS  Google Scholar 

  37. Aimaretti G (2001) Short procedure of GHRH plus arginine test in clinical practice. Pituitary 4:129–134. doi:10.1023/A:1015306705154

    Article  PubMed  CAS  Google Scholar 

  38. Popovic V (2004) Evaluation of the reproducibility of the GHRH plus GHRP-6 test of growth hormone reserve in adults. Clin Endocrinol (Oxf) 60:185–191. doi:10.1046/j.1365-2265.2003.01955.x

    Article  CAS  Google Scholar 

  39. Cordido F (1993) Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity. J Clin Endocrinol Metab 76:819–823. doi:10.1210/jc.76.4.819

    Article  PubMed  CAS  Google Scholar 

  40. Gasperi M (1999) Low dose hexarelin and growth hormone (GH)-releasing hormone as a diagnostic tool for the diagnosis of GH deficiency in adults: comparison with insulin-induced hypoglycemia test. J Clin Endocrinol Metab 84:2633–2637. doi:10.1210/jc.84.8.2633

    Article  PubMed  CAS  Google Scholar 

  41. Mahajan T (2000) A simple test for growth hormone deficiency in adults. J Clin Endocrinol Metab 85:1473–1476. doi:10.1210/jc.85.4.1473

    Article  PubMed  CAS  Google Scholar 

  42. Aimaretti G (2002) Endocrine responses to ghrelin in adult patients with isolated childhood-onset growth hormone deficiency. Clin Endocrinol (Oxf) 56:765–771. doi:10.1046/j.1365-2265.2002.01547.x

    Article  CAS  Google Scholar 

  43. Popovic V (2000) GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults. Lancet 356:1137–1142. doi:10.1016/S0140-6736(00)02755-0

    Article  PubMed  CAS  Google Scholar 

  44. Popovic V (2003) The effectiveness of arginine + GHRH test compared with GHRH + GHRP-6 test in diagnosing growth hormone deficiency in adults. Clin Endocrinol (Oxf) 59:251–257. doi:10.1046/j.1365-2265.2003.01835.x

    Article  CAS  Google Scholar 

  45. Leal A (2002) A single growth hormone (GH) determination is sufficient for the diagnosis of GH-deficiency in adult patients using the growth hormone releasing hormone plus growth hormone releasing peptide-6 test. Clin Endocrinol (Oxf) 57:377–384. doi:10.1046/j.1365-2265.2002.01623.x

    Article  CAS  Google Scholar 

  46. Popovic V (2002) The impact of cranial irradiation on GH responsiveness to GHRH plus GH-releasing peptide-6. J Clin Endocrinol Metab 87:2095–2099. doi:10.1210/jc.87.5.2095

    Article  PubMed  CAS  Google Scholar 

  47. Darzy KH (2003) The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval. J Clin Endocrinol Metab 88:95–102. doi:10.1210/jc.2002-021094

    Article  PubMed  CAS  Google Scholar 

  48. Maghnie M (2001) Relationship between the morphological evaluation of the pituitary and the growth hormone (GH) response to GH-releasing hormone Plus arginine in children and adults with congenital hypopituitarism. J Clin Endocrinol Metab 86:1574–1579. doi:10.1210/jc.86.4.1574

    Article  PubMed  CAS  Google Scholar 

  49. Maghnie M (2008) GHRH plus arginine in the diagnosis of acquired GH deficiency of childhood-onset. J Clin Endocrinol Metab 87:2740–2744. doi:10.1210/jc.87.6.2740

    Article  Google Scholar 

  50. Ham JN (2005) Growth hormone releasing hormone plus arginine stimulation testing in young adults treated in childhood with cranio-spinal radiation therapy. Clin Endocrinol (Oxf) 62:628–632. doi:10.1111/j.1365-2265.2005.02272.x

    Article  CAS  Google Scholar 

  51. Bjork J (2005) The utility of the growth hormone (GH) releasing hormone-arginine test for diagnosing GH deficiency in adults with childhood acute lymphoblastic leukaemia treated with cranial irradiation. J Clin Endocrinol Metab 90:6048–6054. doi:10.1210/jc.2005-0304

    Article  PubMed  CAS  Google Scholar 

  52. Iranmanesh A (1991) Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 73:1081–1088

    PubMed  CAS  Google Scholar 

  53. Veldhuis JD (1991) Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J Clin Endocrinol Metab 72:51–59

    Article  PubMed  CAS  Google Scholar 

  54. Clasey JL (2001) Abdominal visceral fat and fasting insulin are important predictors of 24-hour GH release independent of age, gender, and other physiological factors. J Clinical Endocrinol Metab 86:3845–3852. doi:10.1210/jc.86.8.3845

    Article  CAS  Google Scholar 

  55. Corneli G (2005) The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Eur J Endocrinol 153:257–264. doi:10.1530/eje.1.01967

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. Ghigo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gasco, V., Corneli, G., Rovere, S. et al. Diagnosis of adult GH deficiency . Pituitary 11, 121–128 (2008). https://doi.org/10.1007/s11102-008-0110-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-008-0110-x

Keywords

Navigation