Objective: To investigate the diagnostic value of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) measurements in adult patients with acromegaly and GH deficiency (GHD). Methods: Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients, 34 adult patients with GHD and 150 healthy adults. Disease activity in patients with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance test (OGTT). Among patients with acromegaly, 15 had not been treated previously and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin tolerance test (ITT). Among patients with GHD, 15 were aged 20–40 years (9 men and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and fifty healthy subjects were recruited as a control group. To compare the individual serum IGF-I and IGFBP-3 levels of patients with the results of the gold standard, we calculated age- and sex-corrected standard deviation scores (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean ± 2 SD of the values of healthy control subjects as a diagnostic cutoff, defining 95% specificity. Results: The mean IGF-I and IGFBP-3 SDS levels were significantly higher in active acromegalic patients, both untreated and treated but not cured, than in the control subjects (p < 0.05). The sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4 and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and 100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower than those of the control subjects (IGF-I, –2.2 ± 0.8 vs. 0.0 ± 1.0 SDS, p < 0.0001); IGFBP-3, –1.7 ± 1.2 vs. 0.0 ± 1.0 SDS, p < 0.0001), but there was a considerable overlap between GHD in adults and the controls. In all patients with GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and 52.9%, respectively. In the group of women aged 20–40 years, the sensitivity of IGF-I measurement for the diagnosis of GHD was 100%, although the number of patients was only 6. Conclusion: Both serum IGF-I and IGFBP-3 measurements are comparable to an oral glucose tolerance test in patients with untreated acromegaly, but in acromegalic patients that have undergone surgery and/or radiotherapy, serum IGF-I is more valuable for determining disease activity than serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the diagnosis of GHD in adults, but in women aged 20–40 years serum IGF-I measurement appears to be useful in the diagnosis of GHD.

1.
Quabbe HJ, Schilling E, Helge H: Pattern of growth hormone secretion during a 24-hour fast in normal adults. J Clin Endocrinol Metab 1966;26:1173–1177.
2.
Finkelstein JW, Roffwarg HP, Boyar RM, Kream J, Hellman L: Age-related change in the twenty-four-hour spontaneous secretion of growth hormone. J Clin Endocrinol Metab 1972;35:665–670.
3.
Winer LM, Shaw MA, Baumann G: Basal plasma growth hormone levels in man: New evidence for rhythmicity of growth hormone secretion. J Clin Endocrinol Metab 1990;70:1678–1686.
4.
Earll JM, Sparks LL, Forsham PH: Glucose suppression of serum growth hormone in the diagnosis of acromegaly. JAMA 1967;201:628–630.
5.
Thorner MO, Bengtsson BÅ, Ho KY, Albertsson-Wikland K, Christiansen JS, Faglia G, Irie M, Isaksson O, Jörgensen JO, Ranke M, Rosenfeld R, Shalet S, Takano K, van der Veen EA, Weissberger A: The diagnosis of growth hormone deficiency (GHD) in adults. J Clin Endocrinol Metab 1995;80:3097–3098.
6.
Rahim A, Toogood AA, Shalet SM: The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endocrinol 1996;45:557–562.
7.
Resenfeld RG, Albertsson-Wikland K, Cassorla F, Frasier SD, Hasegawa Y, Hintz RL, Lafranchi S, Lippe B, Loriaux L, Melmed S, Preece MA, Ranke MB, Reiter EO, Rogol AD, Underwood LE, Werther GA: Diagnostic controversy: The diagnosis of childhood growth hormone deficiency revisited. J Clin Endocrinol Metab 1995;80:1532–1540.
8.
Clemmons DR, van Wyk JJ, Ridgway EC, Kliman B, Kjellberg RN, Underwood LE: Evaluation of acromegaly by radioimmunoassay of somatomedin-C. N Engl J Med 1979;301:1138–1142.
9.
Grinspoon S, Clemmons D, Swearingen B, Klibanski A: Serum insulin-like growth factor-binding protein-3 levels in the diagnosis of acromegaly. J Clin Endocrinol Metab 1995;80:927–932.
10.
Hoffman DM, O’Sullivan AJ, Baxter RC, Ho KK: Diagnosis of growth-hormone deficiency in adults. Lancet 1994;343:1064–1068.
11.
Blum WF, Ranke MB: Use of insulin-like growth factor-binding protein 3 for the evaluation of growth disorders. Horm Res 1990;33(suppl 4):31–37.
12.
Daughaday WH, Rotwein P: Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev 1989;10:68–91.
13.
Reiter EO, Lovinger RD: The use of a commercially available somatomedin-C radioimmunoassay in patients with disorders of growth. J Pediatr 1981;99:720–724.
14.
Blum WF, Ranke MB, Kietzman K, Gauggel E, Zeisel HJ, Bierich JR: A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: Its use for diagnosis of GH deficiency. J Clin Endocrinol Metab 1990;70:1292–1298.
15.
Barkan AL, Beitins IZ, Kelch RP: Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: Correlation with the degree of growth hormone hypersecretion. J Clin Endocrinol Metab 1988;67:69–73.
16.
Stoffel-Wagner B, Springer W, Bidlingmaier F, Klingmüller D: A comparison of different methods for diagnosing acromegaly. Clin Endocrinol 1997;46:531–537.
17.
Ochoa R, Mercado M, Chacón X, Fonseca E, Hernández M, Zárate A: Usefulness of insulin-like growth factor binding protein-3 levels to determine acromegaly activity and effectiveness of transsphenoidal pituitary surgery. Arch Med Res 1999;30:303–306.
18.
Chen HS, Lin HD: Serum IGF-I and IGFBP-3 levels for the assessment of disease activity of acromegaly. J Endocrinol Invest 1999;22:98–103.
19.
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.
20.
Charalampaki P, Hildebrandt G, Schaeffer HJ, Schönau E, Klug N: Insulin-like growth factor binding protein-3 levels during early and late follow-up after surgery in acromegalic patients. Exp Clin Endocrinol Diabetes 1998;106:130–134.
21.
Jørgensen JOL, Pedersen SA, Thuesen L, Jørgensen J, Ingemann-Hansen T, Skakkebaek NE, Christiansen JS: Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989;i:1221–1225.
22.
Salomon F, Cuneo RC, Hesp R, Sönksen PH: The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 1989;321:1797–1803.
23.
Cuneo RC, Judd S, Wallace JD, Perry-Keene D, Burger H, Lim-Tio S, Strauss B, Stockigt J, Topliss D, Alford F, Hew L, Bode H, Conway A, Handelsman D, Dunn S, Boyages S, Cheung NW, Hurley D: The Australian multicenter trial of growth hormone (GH) treatment in GH-deficient adults. J Clin Endocrinol Metab 1998;83:107–116.
24.
Juul A, Skakkebœk NE: Prediction of the outcome of growth hormone provocative testing in short children by measurement of serum levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3. J Pediatr 1997;130:197–204.
25.
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;134:352–356.
26.
Bates AS, Evans AJ, Jones P, Clayton RN: Assessment of GH status in adults with GH deficiency using serum growth hormone, serum insulin-like growth factor-I and urinary growth hormone excretion. Clin Endocrinol 1995;42:425–430.
27.
de Boer H, Blok GJ, Popp-Snijders C, van der Veen EA: Diagnosis of growth hormone deficiency in adults. Lancet 1994;343:1645–1646.
28.
Svensson J, Johannsson G, Bengtsson BÅ: Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test. Clin Endocrinol 1997;46:579–586.
29.
Baum HBA, Biller BMK, Katznelson L, Oppenheim DS, Clemmons DR, Cannistraro KB, Schoenfeld DA, Best SA, Klibanski A: 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 1996;81:84–92.
30.
Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP: Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest 1981;67:1361–1369.
31.
Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, Rosen T, Lindstedt G, Lundberg PA, Bengtsson BÅ: Serum insulin-like growth factor I in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol 1994;41:351–357.
32.
Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jørgensen K, Müller J, Hall K, Skakkebæk 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.
33.
Jørgensen JOL, Vahl N, Hansen TB, Skjærbæk C, Fisker S, Ørskov H, Hagen C, Christiansen JS: Determinants of serum insulin-like growth factor I in growth hormone deficient adults as compared to healthy subjects. Clin Endocrinol 1998;48:479–486.
34.
Jasper H, Pennisi P, Vitale M, Mella A, Ropelato G, Chervin A: Evaluation of disease activity by IGF-I and IGF binding protein-3 (IGFBP3) in acromegaly patients distributed according to a clinical score. J Endocrinol Invest 1999;21:29–34.
35.
Reutens AT, Hoffman DM, Leung K, Ho KKY: 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.
36.
Gill MS, Toogood AA, O’Neill PA, Thorner MO, Shalet SM, Clayton PE: Urinary growth hormone (GH), inslulin-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.
37.
Fisker S, Jørgensen JO, Vahl N, Ørskov H, Christiansen JS: Impact of gender and androgen status on IGF-I levels in normal and GH-deficient adults. Eur J Endocrinol 1999;141:601–608.
38.
Ho KY, Weissberger AJ: Secretory patterns of growth hormone according to sex and age. Horm Res 1990;33:7–11.
39.
Friend KE, Hartman ML, Pessoli SS, Clasey JL, Thorner MO: Both oral and transdermal estrogen increase growth hormone release in postmenopausal women. J Clin Endocrinol Metab 1996;81:2250–2256.
40.
Johansson AG, Engström BE, Ljunghall S, Karlsson FA, Burman P: Gender differences in the effects of long term growth hormone (GH) treatment on bone in adults with GH deficiency. J Clin Endocrinol Metab 1999;84:2002–2007.
41.
Lieman HJ, Adel TE, Forst C, Von Hagen S, Santoro N: Effects of aging and estradiol supplementation on GH axis dynamics in women. J Clin Endocrinol Metab 2001;86:3918–3923.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.