Journal of Clinical Endocrinology & Metabolism, Vol 80, 927-932, Copyright © 1995 by Endocrine Society

ARTICLES

Serum insulin-like growth factor-binding protein-3 levels in the diagnosis of acromegaly

S Grinspoon, D Clemmons, B Swearingen and A Klibanski
Neuroendocrine Unit, Massachusetts General Hospital, Boston 02114.

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a GH- dependent protein that binds insulin-like growth factor-I (IGF-I) in the circulation and modulates its action at the tissue level. Because IGFBP-3 is a stable and specific marker of somatotroph function, we hypothesized that it would be a useful biochemical marker in the diagnosis of patients with acromegaly and the assessment of surgical cure. We, therefore, investigated the sensitivity of serum IGFBP-3 levels to detect GH excess in 44 patients with clinical acromegaly and pathologically confirmed somatotroph adenomas, including a cohort of 18 patients with untreated disease evaluated before transsphenoidal surgery and medical therapy. IGFBP-3 levels were compared to IGF-I and random GH levels before and after transsphenoidal surgery. Concordance among IGFBP-3, IGF-I, and GH suppressibility by glucose was also determined. In addition, the response of IGFBP-3 to glucose suppression was investigated. All 18 patients with untreated acromegaly had elevated serum IGFBP-3 levels, ranging from 4,186-10,026 micrograms/L (mean +/- SD, 6566 [plusm] 1800 micrograms/L). There was no overlap with the age-adjusted normative ranges (P = 0.0001 in patients 18-55 yr old and P = 0.0176 in patients > 55 yr old) or with the levels obtained in age-comparable controls (P = 0.0001). In 11% of untreated patients with clinical findings of acromegaly and a pathologically confirmed adenoma, IG-FBP-3 levels were elevated, although GH was suppressed to less than 2 micrograms/L with glucose. In these patients, IGF-I levels were either normal or minimally elevated and considered nondiagnostic. IGFBP-3 and IGF-I levels were correlated in patients with untreated acromegaly (r = 0.650; P = 0.0162) and after transsphenoidal surgery (r = 0.644; P = 0.0001). Neither IGF-I nor IGFBP-3 correlated with random GH levels before surgery. However, both IGF-I (r = 0.471; P = 0.0001) and IGFBP-3 (r = 0.259; P = 0.041) correlated with random GH levels in patients studied more than 1 month after transsphenoidal surgery. IGFBP- 3 and IGF-I levels were concordant with GH suppressibility by glucose (P = 0.0039) and IGFBP-3 decreased with glucose suppression in 7 of 10 patients. These data indicate that IGFBP-3 is a sensitive physiological marker of somatotroph function and is concordant with glucose suppression and IGF-I levels before and after transsphenoidal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				K. M Morrison, M. Bidlingmaier, S. Stadler, Z. Wu, L. Skriver, and C. J Strasburger Sample pre-treatment determines the clinical usefulness of acid-labile subunit immunoassays in the diagnosis of growth hormone deficiency and acromegaly Eur. J. Endocrinol., March 1, 2007; 156(3): 331 - 339. [Abstract] [Full Text] [PDF]

				S. O. Akintoye, M. H. Kelly, B. Brillante, N. Cherman, S. Turner, J. A. Butman, P. G. Robey, and M. T. Collins Pegvisomant for the Treatment of gsp-Mediated Growth Hormone Excess in Patients with McCune-Albright Syndrome J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2960 - 2966. [Abstract] [Full Text] [PDF]

				C. A. Hurty and B. Flatland Feline Acromegaly: A Review of the Syndrome J. Am. Anim. Hosp. Assoc., September 1, 2005; 41(5): 292 - 297. [Abstract] [Full Text] [PDF]

				D. R. Clemmons, K. Chihara, P. U. Freda, K. K. Y. Ho, A. Klibanski, S. Melmed, S. M. Shalet, C. J. Strasburger, P. J. Trainer, and M. O. Thorner Optimizing Control of Acromegaly: Integrating a Growth Hormone Receptor Antagonist into the Treatment Algorithm J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4759 - 4767. [Abstract] [Full Text] [PDF]

				A. C. F. Costa, A. Rossi, C. E. Martinelli Jr., H. R. Machado, and A. C. Moreira Assessment of Disease Activity in Treated Acromegalic Patients Using a Sensitive GH Assay: Should We Achieve Strict Normal GH Levels for a Biochemical Cure? J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3142 - 3147. [Abstract] [Full Text] [PDF]

				S. Melmed CLINICAL PERSPECTIVE: Acromegaly and Cancer: Not a Problem? J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 2929 - 2934. [Full Text] [PDF]

				P. Marzullo, C. Di Somma, K. L. Pratt, J. Khosravi, A. Diamandis, G. Lombardi, A. Colao, and R. G. Rosenfeld 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., July 1, 2001; 86(7): 3001 - 3008. [Abstract] [Full Text] [PDF]

				M. Arosio, S. Garrone, P. Bruzzi, G. Faglia, F. Minuto, and A. Barreca Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3 J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1091 - 1098. [Abstract] [Full Text]

				A. Giustina, A. Barkan, F. F. Casanueva, F. Cavagnini, L. Frohman, K. Ho, J. Veldhuis, J. Wass, K. von Werder, and S. Melmed Criteria for Cure of Acromegaly: A Consensus Statement{dagger} J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 526 - 529. [Abstract] [Full Text]

				P. U. Freda, K. D. Post, J. S. Powell, and S. L. Wardlaw Evaluation of Disease Status with Sensitive Measures of Growth Hormone Secretion in 60 Postoperative Patients with Acromegaly J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3808 - 3816. [Abstract] [Full Text]

				S. Melmed, I. Jackson, D. Kleinberg, and A. Klibanski Current Treatment Guidelines for Acromegaly J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2646 - 2652. [Abstract] [Full Text]

				S. Rajaram, D. J. Baylink, and S. Mohan Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions Endocr. Rev., December 1, 1997; 18(6): 801 - 831. [Abstract] [Full Text]

				A. J. van der Lely and W. W. de Herder The Role of Radiotherapy in Acromegaly J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3185 - 3186. [Full Text] [PDF]

				J. L. Stock, M. R. Warth, B. T. Teh, J. A. Coderre, J. H. Overdorf, G. Baumann, R. L. Hintz, M. L. Hartman, B. R. Seizinger, C. Larsson, et al. A Kindred with a Variant of Multiple Endocrine Neoplasia Type 1 Demonstrating Frequent Expression of Pituitary Tumors but Not Linked to the Multiple Endocrine Neoplasia Type 1 Locus at Chromosome Region 11q13 J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 486 - 492. [Abstract] [Full Text] [PDF]