The current guidelines state that, within the appropriate clinical context, the diagnosis of adult growth hormone (GH) deficiency must be made biochemically using provocative tests. Measurement of insulin-like growth factor I (IGF-I) and binding protein 3 (IGFBP-3) levels cannot always distinguish between healthy and GH-deficient individuals. In particular, IGFBP-3 as a marker of GH status is clearly less sensitive than IGF-I and there is general agreement that its measurement does not provide useful diagnostic information. However, the diagnostic value of measuring IGF-I levels has been revisited recently. It has been confirmed that normal IGF-I levels do not rule out severe GH deficiency (GHD) in adults, in whom the diagnosis has therefore to be based on the demonstration of severe impairment of the peak GH response to provocative tests. It has also been emphasized that very low IGF-I levels in patients with high suspicion of GHD could be considered to be definite evidence for severe GHD. This assumption particularly applies to patients with childhood-onset, severe GHD or with multiple hypopituitary deficiencies acquired in adulthood. In addition, the use of IGF-I levels to monitor the efficacy and adequacy of recombinant human GH replacement remains widely accepted.

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;83:379–381.
AACE medical guidelines for clinical practice for growth hormone use in adults and children. Update Endocrine Practice 2003;9:64–76.
Hoffman DM, O’Sullivan AJ, Baxter RC, Ho KKY: Diagnosis of growth-hormone deficiency in adults. Lancet 1994;343:1064–1068.
Shalet SM, Toogood A, Rahim A, Brennan BMD: The diagnosis of growth hormone deficiency in children and adults. Endocr Rev 1998;19:203–223.
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.
Blum WF, Albertsson-Wikland K, Rosberg S, Ranke MB: Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab 1993;76:1610–1616.
Thorner MO, Vance ML, Laws Jr ER, Horvath E, Kovacs 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, p 165.
Marzullo P, Di Somma C, Pratt KL, Khosravi J, Diamandis A, Lombardi G, Colao A, Rosenfeld RG: 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;86:3001–3008.
Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, Muller J, Hall K, Skakkebaek NE: Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994;78:744–752.
Juul A, Holm K, Kastrup KW, Pedersen SA, Michaelsen KF, Scheike T, Rasmussen S, Muller J, Skakkebaek NE: Free insulin-like growth factor I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency. J Clin Endocrinol Metab 1997;82:2497–2502.
Giustina A, Veldhuis JD: Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 1998;19:717–797.
Le Roith D, Bondy C, Yakar S, Liu JL, Butler A: The somatomedin hypothesis: 2001. Endocr Rev 2001;22:53–74.
Toogood AA: Growth hormone (GH) status and body composition in normal ageing and in elderly adults with GH deficiency. Horm Res 2003;60(suppl 1):105–111.
Thissen JP, Ketelslegers JM, Maiter D: 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 1996;6:222–229.
Jones JI, Clemmons DR: Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995;16:3–34.
Ketelslegers JM, Maiter D, Maes M, Underwood LE, Thissen JP: Nutritional regulation of insulin-like growth factor-I. Metabolism 1995;44(10 suppl 4):50–57.
Ross RJ: GH, IGF-I and binding proteins in altered nutritional states. Int J Obes Relat Metab Disord 2000;24(suppl 2):S92–S95.
Johansson AG: Gender difference in growth hormone response in adults. J Endocrinol Invest 1999;22(5 suppl):58–60.
Dall R, Longobardi S, Ehrnborg C, Keay N, Rosen T, Jorgensen JO, Cuneo RC, Boroujerdi MA, Cittadini A, Napoli R, Christiansen JS, Bengtsson BA, Sacca L, Baxter RC, Basset EE, Sonksen PH: The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. GH-2000 Study Group. J Clin Endocrinol Metab 2000;85:4193–4200.
Span JP, Pieters GF, Sweep CG, Hermus AR, Smals AG: Gender difference in insulin-like growth factor I response to growth hormone (GH) treatment in GH-deficient adults: role of sex hormone replacement. J Clin Endocrinol Metab 2000;85:1121–1125.
Jenkins RC, Ross RJ: Acquired growth hormone resistance in adults. Baillieres Clin Endocrinol Metab 1998;12:315–329.
Hasegawa Y, Hasegawa T, Aso T, Kotoh S, Tsuchiya Y, Nose O, Ohyama Y, Araki K, Tanaka T, Saisyo S: Comparison between insulin-like growth factor-I (IGF-I) and the IGF binding protein-3 measurement in the diagnosis of growth hormone deficiency. Endocr J 1993;40:85–190.
Juul A, Dalgaard P, Blum WF, Bang P, Hall K, Michaelsen KF, Muller J, Skakkebaek NE: Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab 1995;80:2534–2542.
De Boer H, Blok GJ, Popp-Snjders C, Stuurman L, Baxter RC, Van der Veen EA: Monitoring of growth hormone replacement therapy in adults, based on measurement of serum markers. J Clin Endocrinol Metab 1996;81:1372–1377.
Thoren M, Hilding A, Baxter RC, Degerblad M, Wivall-Helleryd IL, Hall K: Serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and the acid-labile subunit as serum markers of body composition during growth hormone (GH) therapy in adults with GH deficiency. J Clin Endocrinol Metab 1997;82:223–228.
Janssen JA, van der Lely AJ, Lamberts SW: Circulating free insulin-like growth-factor-I (IGF-I) levels should also be measured to estimate the IGF-I bioactivity. J Endocrinol Invest 2003;26:588–594.
Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S: Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 2000;85:526–529.
Melmed S, Casanueva FF, Cavagnini F, Chanson P, Frohman L, Grossman A, Ho K, Kleinberg D, Lamberts S, Laws E, Lombardi G, Vance ML, Werder KV, Wass J, Giustina A: Acromegaly Treatment Consensus Workshop Participants. Guidelines for acromegaly management. J Clin Endocrinol Metab 2002;87:4054–4058.
Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C, Bellone J, Camanni F, Ghigo E: Usefulness of IGF-I assay for the diagnosis of GH deficiency in adults. J Endocrinol Invest 1998;21:506–511.
Granada ML, Murillo J, Lucas A, Salinas I, Llopis MA, Castells I, Foz M, Sanmarti A: 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 2000;142:243–253.
Aimaretti G, Corneli G, Baldelli R, Di Somma C, Gasco V, Durante C, Ausiello L, Rovere S, Grottoli S, Tamburrano G, Ghigo E: 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.
Abs R: Update on the diagnosis of GH deficiency in adults. Eur J Endocrinol 2003;148 (suppl 2):S3–S8.
Corneli G, Baldelli R, Di Somma C, Rovere S, Gaia D, Pellegrino M, Gasco V, Durante C, Grottoli S, Colao A, Tamburrano G, Lombardi G, Ghigo E, Aimaretti G: Occurrence of GH deficiency in adult patients who underwent neurosurgery in the hypothalamus-pituitary area for non-functioning tumour masses. Growth Horm IGF Res 2003;13:104–108.
De Boer H, Blok G, van der Veen EA: Clinical aspects of growth hormone deficiency in adults. Endocr Rev 1995;16:63–86.
Lamberts SW, de Herder WW, van der Lely AJ: Pituitary insufficiency. Lancet 1998;352:127–134.
Aimaretti G, Corneli G, Bellone S, Baffoni C, Camanni F, Ghigo E: Growth hormone deficiency in the transition adolescent: Should treatment be continued in adult life? J Pediatr Endocrinol Metab 2001;14(suppl 5):1233–1242;discussion 1261–1262.
Rosenfeld RG: Transitioning patients with childhood-onset growth hormone deficiency to treatment in adulthood. J Pediatr Endocrinol Metab 2002;15(suppl 5):1361–1365.
Leong GM, Johannsson G: Growth hormone deficiency: strategies and indications to continue growth hormone therapy in transition from adolescence to adult life. Horm Res 2003;60(suppl 1):78–85.
Benvenga S, Campenni A, Ruggeri RM, Trimarchi F: Clinical review 113: Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 2000;85:1353–1361.
Gasperi M, Aimaretti G, Cecconi E, Colao A, Di Somma C, Cannavo S, Baffoni C, Cosottini M, Curto L, Trimarchi F, Lombardi G, Grasso L, Ghigo E, Martino E: Impairment of GH secretion in adults with primary empty sella. J Endocrinol Invest 2002;25:329–333.
Gasperi M, Cecconi E, Grasso L, Bartalena L, Centoni R, Aimaretti G, Broglio F, Miccoli P, Marcocci C, Ghigo E, Martino E: GH secretion is impaired in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 2002;87:1961–1964.
Fisker S, Jorgensen JO, Christiansen JS: Variability in growth hormone stimulation tests. Growth Horm IGF Res 1998;8(suppl A):31–35.
Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C, Arvat E, Camanni F, Ghigo E: Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. J Clin Endocrinol Metab 1998;83:1615–1618.
Reutens AT, Hoffman DM, Leung KC, Ho KK: Evaluation and application of a highly sensitive assay for serum growth hormone (GH) in the study of adult GH deficiency. J Clin Endocrinol Metab 1995;80:480–485.
Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ; HyposCCS Advisory Board; 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;87:477–485.
Skjaerbaek C, Vahl N, Frystyk J, Hansen TB, Jorgensen JO, Hagen C, Christiansen JS, Orskov H: Serum free insulin-like growth factor-I in growth hormone-deficient adults before and after growth hormone replacement. Eur J Endocrinol 1997;137:132–137.
Musolino NR, Da Cunha Neto MB, Marino Junior R, Giannella-Neto D, Bronstein MD: Evaluation of free insulin-like growth factor-I measurement on the diagnosis and follow-up treatment of growth hormone-deficient adult patients. Clin Endocrinol (Oxf) 1999;50:441–449.
Corpas E, Harman SM, Blackman MR: Human growth hormone and human aging. Endocr Rev 1993;14:20–39.
Ghigo E, Arvat E, Gianotti L, Ramunni J, DiVito L, Maccagno B, Grottoli S, Camanni F: Human aging and the GH-IGF-I axis. J Pediatr Endocrinol Metab 1996;9(suppl 3):271–278.
Svensson J, Johannsson G, Bengtsson BA: Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal value, body composition and insulin tolerance test. Clin Endocrinol (Oxf) 1997;46:579–586.
Maccario M, Tassone F, Gauna C, Oleandri SE, Aimaretti G, Procopio M, Grottoli S, Pflaum CD, Strasburger CJ, Ghigo E: Effects of short-term administration of low-dose rhGH on IGF-I levels in obesity and Cushing’s syndrome: Indirect evaluation of sensitivity to GH. Eur J Endocrinol 2001;144:251–256.
Aimaretti G, Fanciulli G, Bellone S, Maccario M, Arvat E, Delitala G, Camanni F, Ghigo E: Enhancement of the peripheral sensitivity to growth hormone in adults with GH deficiency. Eur J Endocrinol 2001;145:267–272.
Svensson J, Veldhuis JD, Iranmanesh A, Bengtsson BA, Johannsson G: Increased orderliness of growth hormone (GH) secretion in GH-deficient adults with low serum insulin-like growth factor I. J Clin Endocrinol Metab 2002;87:2863–2869.
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 1994;41:511–516.
Attanasio AF, Lamberts SW, Matranga AM, Birkett MA, Bates PC, Valk NK, Hilsted J, Bengtsson BA, Strasburger CJ: Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group. J Clin Endocrinol Metab 1997;82:82–88.
Attanasio AF, Howell S, Bates PC, Frewer P, Chipman J, Blum WF, Shalet SM: 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 2002;87:3368–3372.
Hilding A, Hall K, Wivall-Helleryd IL, Saaf M, Melin AL, Thoren M: 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 1999;84:2013–2019.
Boquete HR, Sobrado PG, Fideleff HL, Sequera AM, Giaccio AV, Suarez MG, Ruibal GF, Miras M: 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 2003;88:4702–4708.
Fukuda I, Hizuka N, Itoh E, Yasumoto K, Ishikawa Y, Murakami Y, Sata A, Takano K: Acid-labile subunit in growth hormone excess and deficiency in adults: Evaluation of its diagnostic value in comparison with insulin-like growth factor (IGF)-I and IGF-binding protein-3. Endocr J 2002;49:379–386.
Mukherjee A, Monson JP, Jonsson PJ, Trainer PJ, Shalet SM, KIMS International Board: Seeking the optimal target range for insulin-like growth factor I during the treatment of adult growth hormone disorders. J Clin Endocrinol Metab 2003;88:5865–5870.
Gargosky SE, Hasegawa T, Tapanainen P, MacGillivray M, Hasegawa Y, Rosenfeld RG: Urinary insulin-like growth factors (IGF) and IGF-binding proteins in normal subjects, growth hormone deficiency, and renal disease. J Clin Endocrinol Metab 1993;76:1631–1637.
Spagnoli A, Gargosky SE, Spadoni GL, MacGillivray M, Oh Y, Boscherini B, Rosenfeld RG: Characterization of a low molecular mass form of insulin-like growth factor binding protein-3 (17.7 kilodaltons) in urine and serum from healthy children and growth hormone (GH)-deficient patients: Relationship with GH therapy. J Clin Endocrinol Metab 1995;80:3668–3676.
Gill MS, Toogood AA, O’Neill PA, Thorner MO, Shalet SM, Clayton PE: Urinary growth hormone (GH), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 measurements in the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 1998;83:2562–2565.
Baxter RC: IGF binding protein-3 and the acid-labile subunit: Formation of the ternary complex in vitro and in vivo. Adv Exp Med Biol 1993;343:237–244.
You do not currently have access to this content.