Abstract
The diagnosis of GH deficiency (GHD) in adults is established by laboratory testing in patients with an appropriate clinical history of hypothalamic pituitary disease. As the measurement of IGF-I and IGFBP-3 levels as well as the spontaneous GH secretion are not considered reliable parameters, the diagnosis of GHD in adults may be established by GH provocative tests, provided that a reproducible test with clear normative limits is available. The insulin tolerance test (ITT) is a reliable diagnostic test in adults, but is contraindicated in several clinical conditions which are often observed in adult patients with suspected GHD. The other classic GH provocative tests, except the glucagon test, have a poor diagnostic utility and should be abandoned. GHRH combined with arginine or GH secretagogues represent a potent, safe, reproducible and reliable test which should be preferable to the ITT as a first-choice diagnostic test for GHD.
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De Boer H, Blok GJ, Van der Veen E. Clinical aspects of growth hormone deficiency in adults. Endoc Rev 1995, 16: 63–86.
Cuneo RC, Judd S, Wallace JD, et al. The Australian multicenter trial of growth hormone (GH) treatment in GH-deficient adults. J Clin Endocrinol Metab 1998, 83: 107–16.
Hartman ML, Crowe BJ, Biller BMK, Ho KKY, Clemmons DR, Chipman JJ, on behalf of the HypoCCS Advisory Board and the US HypoCCS Study Group. Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab 2002, 87: 477–85.
Thorner MO, Vance ML, Laws Jr ER, Horvath E, Kovavs K. The anterior pituitary. In: Wilson JD, Foster DW, Kronenberg HM, Reed Larsen P eds. Williams textbook of Endocrinology. 9th ed. Philadelphia: WB Saunders Company. 1998, 165.
Growth hormone Research Society (GRS). Consensus guidelines for the diagnosis and treatment of adults with GH deficiency. Statement of the GRS workshop on adult GHD. J Clin Endocrinol Metab 1998, 83: 379–81.
Marzullo P, Di Somma C, Pratt KL, et al. Usefulness of different biochemical markers of the insulin-like growth factor (IGF) family in diagnosing growth hormone excess and deficiency in adults. J Clin Endocrinol Metab 2001, 86: 3001–8.
Shalet SM, Toogood A, Rahim A, Brennan BM. The diagnosis of growth hormone deficiency in children and adults. Endocr Rev 1998, 19: 203–23.
Aimaretti G, Corneli G, Baldelli R, et al. Diagnostic reliability of a single IGF-I measurement in 237 adults with total anterior hypopituitarism and severe GH deficiency. Clin Endocrinol (Oxf) 2003, 59: 56–61.
Gharib H, Cook DM, Saenger PH, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children-2003 update. Endocr Pract 2003, 9: 64–76.
Hoffman DM, O’Sullivan AJ, Baxter RC, Ho KKY. Diagnosis of growth hormone deficiency in adults. Lancet 1994, 343: 1064–8.
Hoeck HC, Vestergaard P, Jakobson PE, Laurberg P. Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test. Eur J Endocrinol 1995, 133: 305–12.
Aimaretti G, Baffoni C, DiVito L, et al. Comparisons among old and new provocative tests of GH secretion in 178 normal adults. Eur J Endocrinol 2000, 142: 347–52.
Rahim A, Toogood, Shalet SM. The assessment of growth hormone in normal young adult males using a variety of provocative agents. Clin Endocrinol (Oxf) 1996, 45: 557–62.
Biller BMK, Samnels MH, Zagar A, et al. Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 2002, 87: 2067–79.
Gomez JM, Espadero RM, Escobar-Jiménez F, et al. Growyh hormone release after glucagons as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf) 2002, 56: 329–34.
Conceicao FL, da Costa e Silva A, Leal Costa AJ, Vaisman M. Glucagon stimulation test for the diagnosis of GH deficiency in adults J Endocrinol Invest 2003, 26: 1065–70.
Massara F, Ghigo E, Demislis K, et al. Cholinergic involvement in the growth hormone releasing hormone-induced growth hormone release: studies in normal and acromegalic subjects. Neuroendocrinology 1986, 43: 670–5.
Ghigo E, Bellone J, Mazza E, et al. Arginine potentiates the GHRH — but not the piridostigmine-induced-GH secretion in normal short children. Further evidence for a somatostatin suppressing effect of arginine. Clin Endocrinol (Oxf) 1990, 32: 763–7.
Ghigo E, Bellone J, Aimaretti G, et al. Reliability of provocative tests to assess growth hormone secretory status in 472 normally growing children. J Clin Endocrinol Metab 1996, 81: 3323–7.
Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F. New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 1996, 134: 352–6.
Valetto MR, Bellone J, Baffoni C, et al. Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan. Eur J Endocrinol 1996, 135: 568–72.
Ghigo E, Aimaretti G, Arvat E, Camanni F. Growth hormone-releasing hormone combined with arginine or growth hormone secretagogues for the diagnosis of growth hormone deficiency in adults. Endocrine 2001, 15: 29–38.
Aimaretti G, Bellone S, Baffoni C, et al. Short procedure of GHRH plus arginine test in clinical practice. Pituitary 2001, 4: 129–34.
Aimaretti G, Corneli G, Di Somma C, et al. Different degrees of GH deficiency evidenced by GHRH-arginine test and IGF-I levels in adults with pituitary disease. J Endocrinol Invest 2005, 28: 247–52.
Toogood AA, Beardwell CG, Shalet SM. The severity of growth hormone deficiency in adults with pituitary disease is related to the degree of hypopituitarism. Clin Endocrinol (Oxf) 1994, 41: 511–6.
Colao A, Di Somma C, Pivonello R, et al. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 1999, 84: 1919–24.
Colao A, Carbone G, Pivonello R, et al. 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 1999, 84: 1277–82.
Colao A, Di Somma C, Cuocolo A, et al. 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 2004, 89: 5998–6004.
Kopelman PG, Noonan K, Goulton R, Forrest AJ. Impaired growth hormone response to growth hormone releasing factor and insulin-hypoglycaemia in obesity. Clin Endocrinol (Oxf) 1985, 23: 87–94.
Ghigo E, Procopio M, Boffano GM, et al. Arginine potentiates but does not restore the blunted growth hormone response to growth hormone-releasing hormone in obesity. Metabolism 1992, 41: 560–3.
Bonert VS, Elashoff JD, Barnett P, Melmed S. Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: diagnostic caveat for adult GH deficiency. J Clin Endocrinol Metab 2004, 89: 3397–401.
Qu XD, Gaw Gonzalo IT, Al Sayed MJ, et al. 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 2005, 90: 1 563–9.
Corneli G, Di Somma C, Baldelli R, et al. The cut-off limits of the GH response to GHRH-arginine test related to body mass index. Eur J Endocrinol 2005, 153: 257–64.
Bidlingmaier M, Wu Z, Strasburger CJ. Test method: GH. Baillieres Best Pract Res Clin Endocrinol Metab 14: 99–109.
Camanni F, Ghigo E, Arvat E. Growth hormone-releasing peptides and their analogs. Front Neuroendocrinol 1998, 19: 47–72.
Gasperi M, Aimaretti G, Scarcello S, et al. Low dose hexarelin+GHRH as diagnostic tool for the diagnosis of GH deficiency (GHD) in adults. Comparison with insulin-induced hypoglycaemia test. J Clin Endocrinol Metab 1999, 84: 2633–7.
Casanueva FF, Dieguez C. Growth hormone secretagogues: physiological role and clinical utility. Trends Endocrinol Me-tab 1999, 10: 30–8.
Micic D, Popovic V, Doknic M, Macut D, Dieguez C, Casanueva FF. Preserved Growth Hormone (GH) Secretion in Aged and Very Old Subjects after Testing with the Combined Stimulus GH-Releasing Hormone plus GH-Releasing Hexa-peptide-6. J Clin Endocrinol Metab 1998, 83: 2569–72.
Haijma SV, Van Dam PS, De Vries Wr, et al. The GHRH/ GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men. Eur J Endocrinol 2005, 152: 575–80.
Mahajan T, Lightman SL. A Simple Test for Growth Hormone Deficiency in adults. J Clin Endocrinol Metab 2000, 85: 1473–6.
Popovic V, Leal A, Micic D, et al. GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults. Lancet 2002, 356: 1137–42.
Popovic V, Damjanovic S, Micic D, Djurovic M, Dieguez C, Casanueva FF. Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamo-pituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level. J Clin Endocrinol Metab 1995, 80: 942–7.
Darzy KH, Aimaretti G, Wieringa G, Rao Gattamaneni H, Ghigo E, Shalet SM. 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 2003, 88: 95–102.
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Camanni, F. Diagnosis of adult growth hormone deficiency: Still a matter of debate. J Endocrinol Invest 29, 190–194 (2006). https://doi.org/10.1007/BF03344096
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DOI: https://doi.org/10.1007/BF03344096