Abstract
IGF-I is the best marker of GH secretory status but it also depends on the nutritional status and peripheral hormones such as insulin, glucocorticoids, thyroid hormones and gonadal steroids. Though monitoring IGF-I levels is the best way for evaluating appropriate GH replacement, the usefulness of IGF-I assay in the diagnosis of adult GH deficiency (GHD) is still matter of debate. To clarify this point in a large population of GHD adults (no.=135, 61 women and 74 men; age, mean±SE: 43.8±1.4 yr, range 20–80 yr) we studied IGF-I levels, their reproducibility and association to peak GH response to GHRH+arginine (GHRH+ARG) test and insulin tolerance test (ITT). The results in GHD were compared with those in a large population of normal subjects (no.=336, 233 women and 103 men, aged 20–80 yr). Mean IGF-I levels in GHD (77.8±4.9 µg/l) were clearly lower (p<0.001) than those in normal subjects (170.2±4.7 µg/I). In Childhood Onset GHD (CO-GHD; no.=40; age, mean±SE: 27.8±1.5 yr) IGF-I levels were lower than those in Adult Onset GHD (AO-GHD; no.=95, age, mean±SE: 50.7±1.4 yr) (56.6±9.7 vs 87.1 ±5.4 µg/l, p<0.0003). In both GHD and normal subjects IGF-I levels showed good, reproducibility (r=0.92, p<0.00001 and r=0.62, p<0.00001, respectively). In GHD, but not in normal subjects, IGF-I levels were positively associated to peak GH responses to GHRH+ARG (r=0.57, p<0.00001); on the other hand, the GH peak after ITT was not associated to IGF-I in GHD. In normal subjects, but not in GHD, IGF-I levels were negatively associated to age (r=−0.60, p<0.00001). Considering individual IGF-I levels there was a clear overlap between GHD and normal subjects. However, this overlap was strongly dependent on age. In fact, in the third and fourth decade of life 83.6% of GHD had IGF-I levels below the 3rd centile of normal values; on the other hand, in the fifth-sixth decade and in ageing 47% and only 12% of GHD, respectively, had IGF-I levels low for age. In conclusion, our results demonstrate that IGF-I levels represent a reproducible marker of GH status and are reduced more in CO-GHD than in AO-GHD adults. An overlap exists between GHD and normal subjects, however this is small up to the 4th decade of life. Thus, though normal IGF-I levels do not rule out the existence of GHD, up to 40 yr low IGF-I levels strongly point to GHD if malnutrition and liver disease have been ruled out.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Blum W.F., Albertson-Wikland K., Rosberg S., Ranke M.B. Serum levels of Insulin-Like Growth Factor I (IGF-I) and IGF-binding protein 3 reflect spontaneous growth hormone secretion. J. Clin. Endocrinol. Metab. 76: 1610, 1993.
Jones J., Clemmons D.R. Insulin-like growth factor and their binding proteins: biological actions. Endocr. Rev. 16: 3, 1995.
Ketelslegers S.M., Maiter D., Maes M., Underwood L.E., Thissen J.P. Nutritional regulation of Insulin-Like-Growth-Factor-I. Metabolism 44(suppl. 4): 50, 1995.
Thissen J.P., Ketelslegers J.M., Underwood L.E. Nutritional regulation of the insulin like growth factors. Endocr. Rev. 15: 80, 1994.
Minuto F., Barreca A., Adami G.F., Fortini F., Del Monte P., Cella F., Scopinaro N., Giordano G. Insulin-like-growth-factor-l in human malnutrition: relationship with some body composition and nutritional parameters. J. Parenter. Nutr. 13: 392, 1989.
Underwood L.E., Van Wyk J.J. Normal and aberrant growth. In: Wilson J.D., Foster D.W., (Eds.), Williams Text-book of Endocrinology, ed. 8. Saunders Co., Philadelphia, 1992, p. 1079.
De Boer H., Blok J.G., Van der Veen E.A. Clinical aspects of growth hormone deficiency in adults. Endocr. Rev. 16: 63, 1995.
De Boer H., Blok J.G., Popp-Snijders C., Stuurman L., Baxter R.C., Van der Veen E.A. Monitoring of growth hormone replacement therapy in adults, based on measurement of serum marker. J. Clin. Endocrinol. Metab. 81: 1371, 1996.
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. 83: 379, 1998.
Hoffman D.M., O’Sullivan A.J., Baxter R.C., Ho K.Y. Diagnosis of growth hormone deficiency in adults. Lancet i: 1064, 1994.
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. 134: 352, 1996.
Bates A.S., Evans A.J., Jones P., Clayton R.N. Assessment of GH status in adults with GH deficiency using serum growth hormone, serum insulin-like growth factor-l and urinary growth hormone secretion. Clin. Endocrinol. (Oxf.) 42: 424, 1995.
Svensson J., Johannsson G., Bengtsson B.A. Insulin-like growth factor-l in growth hormone-deficient adults: relationship to population-based normal value, body composition and insulin tolerance test. Clin. Endocrinol. (Oxf.) 46: 579, 1997.
Ghigo E., Bellone J., Aimaretti G., Bellone S., Loche S., Cappa M., Bartolotta E., Darnmacco F., Camanni F. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J. Clin. Endocrinol. Metab. 81: 3323, 1996.
Valetto M.R., Bellone J., Baffoni C., Savio P., Aimaretti G., Gianotti L., Arvat E., Camanni F., Ghigo E. Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan. Eur. J. Endocrinol. 135: 568, 1996.
Goodman-Gruen D., Barret-Connor E. Epidemiology of insulin-like growth factor-l in elderly men and women. The Rancho Bernardo Study. Am. J. Epidemiol. 145: 970, 1997.
Attanasio A.F., Lamberts S.W.J., Matranga A.M.C., Birkett M.A., Bares P.C., Valk N.K., Hilsted J., Bengtsson B.A., Strasburgher C.J. and the Adult Growth Hormone Study Group. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during Human GH treatment. J. Clin. Endocrinol. Metab. 81: 82, 1997.
Landim-Wilhelmsen K., Wilhelmsen L., Lappas G., Rosen T., Lindstedt G., Lundberg P.A., Bengtsson B.A. Serum insulin-like growth factor l 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. (Oxf.) 41: 351, 1994.
Corpas E., Hartman S.M., Blackman S. Human growth hormone and human ageing. Endocr. Rev. 14: 20, 1993.
Veldhuis J.D. New modalities for understanding dynamic regulation of the somatotropic (GH) axis: explication of gender differences in GH neuroregulation in the human. J. Ped. Endocrinol. Metab. 9: 237, 1996.
Thorner M.O., Bengtsson B.A., Ho K.K.Y., Albertsson-Wikland K., Christiansen J.S., Faglia G., Irie M., Isaksson O., Jorgensen J.O.L., Ranke M., Rosenfeld R., Shalet S., Takano K., Van der Veen E.A., Weissberger A. Diagnosis of growth hormone deficiency in adults. J. Clin. Endocrinol. Metab. 80: 3097-1995.
Toogood A.A., O’Neill P.A., Shalet S.M. Beyond the somatopause: growth hormone deficiency adults over the age of 60 years. J. Clin. Endocrinol. Metab. 81: 460, 1996.
Bengtsson B.A. Growth hormone deficiency in adults: a new indication of recombinant human growth hormone. J. Int. Med. 239: 283, 1996.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Aimaretti, G., Corneli, G., Razzore, P. et al. Usefulness of IGF-I assay for the diagnosis of GH deficiency in adults. J Endocrinol Invest 21, 506–511 (1998). https://doi.org/10.1007/BF03347336
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347336