Serum insulin-like growth factor I (IGF-I) is an important marker of disease activity in patients with acromegaly, and epidemiological data indicate control of circulating IGF-I in patients with acromegaly restores life expectancy to normal. Improvements in the quality of, and access to, IGF-I assays has encouraged monitoring of acromegaly with IGF-I, although circulating growth hormone (GH) and IGF-I values provide different information, so ideally both should be monitored. However, the introduction of the GH receptor antagonist pegvisomant poses new challenges. Pegvisomant binds with high affinity to GH receptors, thereby blocking the action of GH at the tissue level and rendering the hormone biologically inactive. This leaves IGF-I as the principal marker of disease activity. It is conceptually possible to induce a state of functional GH deficiency (GHD) with pegvisomant with IGF-I values within the normal range. With the goal of minimizing the risk of over-treatment and GHD, we have provided preliminary guidance on the target range for IGF-I in patients receiving pegvisomant based on the gender- and decade-based percentile ranges for IGF-I of adult patients with untreated GHD enrolled in the Pfizer International Metabolic Database (KIMS).

Journal Section:
Efficacy
Keywords:
Adults, Acromegaly, Growth hormone, Insulin-like growth factor I, KIMS, Monitoring
1.
Trainer PJ: Acromegaly-consensus, what consensus? J Clin Endocrinol Metab 2002;87:3534–3536.
[PubMed]
https://doi.org/10.1210%2Fjc.87.8.3534
2.
Bates AS, Van’t Hoff W, Jones JM, Clayton RM: An audit of outcome of treatment in acromegaly. QJ Med 1993;86:293–299.
[PubMed]
3.
Orme SM, McNally RJQ, Cartwright RA, Belchetz PE: Mortality and cancer incidence in acromegaly: A retrospective cohort study. J Clin Endocrinol Metab 1998;83:2730–2734.
[PubMed]
https://doi.org/10.1210%2Fjc.83.8.2730
4.
Swearingen B, Barker FG 2nd, Katznelson L, Biller BM, Grinspoon S, Klibanski A, Moayeri N, Black PM, Zervas NT: Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 1998;83:3419–3426.
[PubMed]
https://doi.org/10.1210%2Fjc.83.10.3419
5.
Beauregard C, Truong U, Hardy J, Serri O: Long-term outcome and mortality after transsphenoidal adenectomy for acromegaly. Clin Endocrinol 2003;58:86–91.
[PubMed]
https://doi.org/10.1046%2Fj.1365-2265.2003.01679.x
6.
Holdaway IM, Rajasoorya CR, Gamble GD, Stewart AW: Long-term treatment outcome in acromegaly. Growth Horm IGF Res 2003;13:185–192.
[PubMed]
https://doi.org/10.1016%2FS1096-6374%2803%2900030-3
7.
Clemmons DR: Commercial assays available for insulin-like growth factor I and their use in diagnosing growth hormone deficiency. Horm Res 2001;55:73–79.
[PubMed]
https://doi.org/10.1159%2F000063480
8.
Blum WF, Ranke MB, Bierich JR: A specific radioimmunoassay for insulin-like growth factor II: the interference of IGF binding proteins can be blocked by excess IGF-I. Acta Endocrinol 1988;118:374–380.
[PubMed]
9.
Blum WF, Breier BH: Radioimmunoassays for IGFs and IGFBPs. Growth Regul 1994;4:11–19.
[PubMed]
10.
Chestnut RE, Quarmby V: Evaluation of total IGF-I assay methods using samples from type I and type II diabetic patients. J Immunol Methods 2002;259:11–24.
[PubMed]
https://doi.org/10.1016%2FS0022-1759%2801%2900478-1
11.
Rojdmark S, Brismar K: Decreased IGF-I bioavailability after ethanol abuse in alcoholics: partial restitution after short-term abstinence. J Endocrinol Invest 2001;24:476–482.
[PubMed]
12.
Muller AF, Jansenn JA, Hofland LJ, Lamberts SW, Bidlingmaier M, Strasburger CJ, van der Lely AJ: Blockade of the growth hormone (GH) receptor unmasks rapid GH-releasing peptide-6-mediated tissue-specific insulin resistance. J Clin Endocrinol Metab 2001;86:590–593.
[PubMed]
https://doi.org/10.1210%2Fjc.86.2.590
13.
Brabant G, von zur Muhlen A, Wuster C, Ranke MB, Kratzsch J, Kiess W, Ketelslegers J, Wilhelmsen L, Hulthen L, Saller B, Mattsson A, Wilde J, Schemer R, Kann P: Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicentre study. Horm Res 2003;60:53–60.
[PubMed]
https://doi.org/10.1159%2F000071871
14.
Holly JM, Cotterill AM, Jemmott RC, Shears D, al-Othman S, Chard T, Wass JA: Inter-relations between growth hormone, insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1) and sex hormone-binding globulin in acromegaly. Clin Endocrinol (Oxf) 1991;34:275–280.
[PubMed]
https://doi.org/10.1111%2Fj.1365-2265.1991.tb03766.x
15.
Parkinson C, Ryder WDJ, Trainer PJ and the sensus acromegaly study group: The relationship between serum GH and serum IGF-I in acromegaly is gender-specific. J Clin Endocrinol Metab 2001;86:5240–5244.
[PubMed]
https://doi.org/10.1210%2Fjc.86.11.5240
16.
Parkinson C, Renehan AG, Ryder WD, O’Dwyer ST, Shalet SM, Trainer PJ: Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly. Clin Endocrinol (Oxf) 2002;57:59–64.
[PubMed]
https://doi.org/10.1046%2Fj.1365-2265.2002.01560.x
17.
Peacey SR, Toogood AA, Veldhuis JD, Thorner MO, Shalet SM: The relationship between 24-hour growth hormone secretion and insulin-like growth factor I in patients with successfully treated acromegaly: impact of surgery or radiotherapy. J Clin Endocrinol Metab 2001;86:259–266.
[PubMed]
https://doi.org/10.1210%2Fjc.86.1.259
18.
Barkan AL, Halasz I, Dornfeld KJ, Jaffe CA, DeMott Friberg R, Chandler WF, Sandler HM: Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. J Clin Endocrinol Metab 1997;82:3187–3191.
[PubMed]
https://doi.org/10.1210%2Fjc.82.10.3187
19.
Giustina A, Barkan A, Casaneuva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, von Werder K, Melmed S: Criteria for a cure of acromegaly: A consensus statement. J Clin Endocrinol Metab 2000;85:526–529.
[PubMed]
https://doi.org/10.1210%2Fjc.85.2.526
20.
Freda PU, Post KD, Powell JS, Wardlaw SL: Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 1998;83:3808–3816.
[PubMed]
https://doi.org/10.1210%2Fjc.83.11.3808
21.
Serri O, Beauregard C, Hardy J: Long-term biochemical status and disease-related morbidity in 53 postoperative patients with acromegaly. J Clin Endocrinol Metab 2004;89:658–661.
[PubMed]
https://doi.org/10.1210%2Fjc.2003-030915
22.
Dimaraki EV, Jaffe CA, DeMott-Friberg R, Chandler WF, Barkan AL: Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 2002;87:3537–3542.
[PubMed]
https://doi.org/10.1210%2Fjc.87.8.3537
23.
Walker JL, Crock PA, Behncken SN, Rowlinson SW, Nicholson LM, Boulton TJC, Waters MJ: A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-I and luteinizing hormone-releasing hormone analogue. J Clin Endocrinol Metab 1998;83:2554–2561.
[PubMed]
https://doi.org/10.1210%2Fjc.83.7.2554
24.
Backeljauw PF, Underwood LE, and the GHIS collaborative group: Prolonged treatment with recombinant insulin-like growth factor-I in children with growth hormone insensitivity syndrome – a clinical research center study. J Clin Endocrinol Metab 1996;81:3312–3317.
[PubMed]
https://doi.org/10.1210%2Fjc.81.9.3312
25.
Leonard J, Samuels M, Cotterill AM, Savage MO: Effects of recombinant insulin-like growth factor I on craniofacial morphology in growth hormone insensitivity. Acta Paediatr Suppl 1994;399:140–141.
[PubMed]
https://doi.org/10.1111%2Fj.1651-2227.1994.tb13308.x
26.
van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, Thorner MO: Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 2001;358:1754–1759.
[PubMed]
https://doi.org/10.1016%2FS0140-6736%2801%2906844-1
27.
Mukherjee A, Monson JP, Jonsson PJ, Trainer PJ, Shalet SM: 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.
[PubMed]
https://doi.org/10.1210%2Fjc.2002-021741
© 2004 S. Karger AG, Basel
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