Skip to main content
SpringerLink
Log in

Low IGF-I levels are often uncoupled with elevated GH levels in catabolic conditions

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Increased GH together with decreased IGF-I levels pointing to peripheral GH insensitivity in critically ill patients have been reported by some but not by other authors. To clarify whether elevated GH levels are coupled with low IGF-I levels in all catabolic conditions, basal GH and IGF-I levels were evaluated in patients with sepsis (SEP, no.=13; age [mean±SE]=59.2±1.2 yr), trauma (TRA, no.=16; age=42.3±3.4 yr), major burn (BUR, no.=26; age=52.8±4.2 yr) and postsurgical patients (SUR, no.=11; age=55.0±4.7 yr) 72 hours after ICU admission or after cardiac surgery. GH and IGF-I levels were also evaluated in normal subjects (NS, no.=75; age=44.0±1.5 yr), in adult hypopituitaric patients with severe GH deficiency (GHD, no.=54; age=44.8±2.3 yr), in patients with liver cirrhosis (LC, no.=12; age=50.4±2.8 yr) and in patients with anorexia nervosa (AN, no.=19; age=18.7±0.8 yr). Basal IGF-I and GH levels in GHD were lower than in NS (68.6±6.4 vs 200.9±8.7 µg/l and 0.3±0.1 vs 1.4+0.2 µg/l; p<0.01). On the other hand, AN and LC showed IGF-I levels (70.4±9.1 and 52.4±10.5 µg/l) similar to those in GHD while GH levels (10.0±2.8 and 7.9±2.1 µg/l) were higher than those in NS (p< 0.01). IGF-I levels in SEP (84.5±8.8 µg/l) were similar to those in GHD, AN and LC and lower than those in NS (p<0.01). IGF-I levels in BUR (105.2±10.9 µg/l) were lower than in NS (p<0.01) but higher than those in GHD, AN, LC and SEP (p<0.01). On the other hand, in TRA (162.8±17.4 µg/l) and SUR (135.0±20.7 µg/l) IGF-I levels were lower but not significantly different from those in NS and clearly higher than those in GHD, AN, LC, SEP and BUR. Basal GH levels in SEP (0.6±0.2 µg/l), TRA (1.8±0.5 µg/l), SUR (2.2±0.5 µg/l) and BUR (2.2±0.5 µg/l) were similar to those in NS, higher (p<0.05) than those in GHD and lower (p<0.01) than those in AN and LC. In conclusion, our data demonstrate that low IGF-I levels are not always coupled with elevated GH levels in all catabolic conditions. Differently from cirrhotic and anorectic patients, in burned and septic patients GH levels are not elevated in spite of very low IGF-I levels similar to those in panhypopituitaric GHD patients. These findings suggest that in some catabolic conditions peripheral GH insensitivity and somatotrope insufficiency could be concomitantly present.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jenkins R.C., Ross R.J.M. The endocrinology of the critically ill. Curr. Opin. Endocrinol. Diab. 3: 138, 1996.

    Article  Google Scholar 

  2. Dahn M.S., Lange M.P., Jacobs L.A. Insulinlike growth factor-I production is inhibited in human sepsis. Arch. Surg. 123: 1409, 1993.

    Article  Google Scholar 

  3. Belcher H.J.C.R., Mercer D., Judkins K.C., Shalaby S., Wise S., Marks V., Tanner N.S.B. Biosynthetic human growth hormone in burned patients: a pilot study. Burns 15: 99, 1989.

    Article  PubMed  CAS  Google Scholar 

  4. Fleming R.Y.D., Rutan R.L., Jahoor F., Barrow R.E., Wolfe R.R., Herndon D.N. Effect of recombinant human growth hormone on catabolic hormones and free fatty acids following thermal injury. J. Trauma 323: 698, 1992.

    Article  Google Scholar 

  5. Voerman H.J., Strack van Schijndel R.J.M., Groeveld A.B.J., de Boer H., Nauta J.P., van der Veen E.A., Thijis L.G. Effects of recombinant human growth hormone in patients with severe sepsis. Ann. Surg., 216: 648, 1992.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Abribat T., Brazeau P., Davignon I., Garrel D.R. Insulin-like growth factor-I blood levels in severely burned patients: effects of time post injury, age of patient and severity of burn. Clin. Endocrinol. (Oxf.) 2: 583, 1993.

    Article  Google Scholar 

  7. Ross R.J.M., Chew S.L. Acquired growth hormone resistance. Eur. J. Endocrinol. 132: 655, 1995.

    Article  PubMed  CAS  Google Scholar 

  8. Cotterill A.M., Mendel P., Holly J.M.P., Timmins C., Camacho-Hubner S.C., Hughes R.M.J., Ross W.F., Langford R.M. The differential regulation of the circulating levels of the insulin-like growth factors and their binding proteins (IGFBP) 1, 2 and 3 after elective abdominal surgery. Clin. Endocrinol. (Oxf.) 44: 91, 1996.

    Article  CAS  Google Scholar 

  9. Timmins A.C., Cotterill A.M., Cwylan Hughes S.C., Holly R.J.M., Blum W., Hinds C.J. Critical illness is associated with low circulating concentrations of insulin-like growth factors-I and-II, alterations in insulin-like growth factor binding proteins, and induction of an insulin-like growth factor binding protein 3 protease. Crit. Care Med. 9: 1460, 1996.

    Article  Google Scholar 

  10. Bentham J., Rodriguez-Amao J., Ross R.J.M. Acquired growth hormone resistance in patients with hypercatabolism. Horm. Res. 40: 87, 1993.

    Article  PubMed  CAS  Google Scholar 

  11. Merimee T.J., Fineberg S.E. Dietary regulation of human growth hormone secretion. Metabolism 12: 1491, 1973.

    Article  Google Scholar 

  12. Thissen J., Keteslegers J.M., Underwood L.E. Nutritional regulation of the insulin-like growth factors. Endocr. Rev. 15: 80, 1994.

    PubMed  CAS  Google Scholar 

  13. Herndon D.N., Barrow R.E., Kunkle K.R., Broemeling L., Rutan L. Effects of recombinant human growth hormone on donor-site in severely burned children. Ann. Surg. 212: 424, 1990.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Ziegler T.R., Romeau J.L., Young L.S., Fong Y., Marano M., Lowry S.F., Wilmore D.W. Recombinant human growth hormone enhances the metabolic efficacy of parenteral nutrition: a doubleblind, randomized controlled study. J. Clin. Endocrinol. Metab. 74: 865, 1992.

    Article  PubMed  CAS  Google Scholar 

  15. Byrne T.A., Morissey T.B., Gatzen C., Benfell K., Nattakom T.V., Scheltinga M.R., LeBoff M.S., Ziegler T.R., Wilmore D.W. Anabolic therapy with growth hormone accelerates protein gain in surgical patients requiring nutritional rehabilitation. Ann. Surg. 218, 4: 400, 1993.

    Article  Google Scholar 

  16. Mulligan K., Grunfeld C., Hellerstein M.K., Nees R.A., Schambelan M.S. Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection. J. Clin. Endocrinol. Metab. 77: 956, 1993.

    PubMed  CAS  Google Scholar 

  17. Wilmore D.W. Catabolic illness. N. Engl. J. Med. 10: 695, 1991.

    Google Scholar 

  18. Pichard C., Jolliet P., Chevrolet J.C., Romand J.A., Slosman D. Recombinant human growth hormone in chronic and acute respiratory insufficiency. Horm. Res. 46: 222, 1996.

    Article  PubMed  CAS  Google Scholar 

  19. Vara-Thorbeck R., Ruiz-Requena E., Guerrero-Fernandez J.A. Effects of human growth hormone on the catabolic state after surgical trauma. Horm. Res. 45: 55, 1996.

    Article  PubMed  CAS  Google Scholar 

  20. Ross R., Mieli J., Jones J., Matthews D., Preece M., Buchanan C. Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I. Clin. Endocrinol. (Oxf.) 35: 47, 1991.

    Article  CAS  Google Scholar 

  21. Nygren J., Sammann M., Malm M., Efendict S., Hall K., Brismar K., Ljungqvist O. Disturbed anabolic hormonal patterns in burned patients: the relation to glucagon. Clin. Endocrinol. (Oxf.) 43: 491, 1995.

    Article  CAS  Google Scholar 

  22. Donaghy A., Ross R., Gimson A., Hughes S.C., Holly J., Williams R. Growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins 1 and 3 in chronic liver disease. Hepatology 21: 680, 1995.

    PubMed  CAS  Google Scholar 

  23. Frost R.A., Fuhrer J., Steigbigel P., Mariuz P., Lang C.H., Gelato M.C. Wasting in the acquired immune deficiency syndrome is associated with multiple defects in the serum insulin-like growth factor system. Clin. Endocrinol. (Oxf.) 44: 501, 1996.

    Article  CAS  Google Scholar 

  24. Van den Berghe G, de Zegher F., Lauwers P., Veldhuis J.D. Growth hormone secretion in critical illness: Effect of dopamine. J. Clin. Endocrinol. Metab. 79: 1141, 1994.

    PubMed  Google Scholar 

  25. Van den Berghe G, de Zegher F. Anterior pituitary function during crtitical illness and dopamine treatment. Crit. Care Med. 24: 1580, 1996.

    Article  PubMed  Google Scholar 

  26. Jeevanandam M., Ramis L., Shamos R.F., Schiller W.R. Decreased growth hormone levels in the catabolic phase of severe iniury. Surgery 11 1: 495, 1992.

    Google Scholar 

  27. Jeffries M.K., Lee Vance M. Growth hormone and Cortisol secretion in patients with burn injury. J. Burn Care Rehabil. 13: 391, 1992.

    Article  PubMed  CAS  Google Scholar 

  28. Voerman H.J., Groeneveld A.B., de Boer H., Strack van Schijndel R.J.M., Nauta J.P., van der Veen E.A., Thijs L.G. Time course and variability of the endocrine and metabolic response to severe sepsis. Surgery 114: 951, 1993.

    PubMed  CAS  Google Scholar 

  29. Melarvie S., Jeevanandam M.L., Holaday N.J., Petersen S.R. Pulsatile nature of growth hormone levels in critically ill trauma victims. Surgery 117: 402, 1995.

    Article  PubMed  CAS  Google Scholar 

  30. Heijligenberg R., Sauerwein H.P., Brabant G., Endertm E., Hommes M.J., Romijn J.A. Circadian growth hormone secretion in asymptomatic human immune deficiency virus infection and acquired immunodeficiency syndrome. Clin. Endocrinol. Metab. 81: 4028, 1996.

    CAS  Google Scholar 

  31. Casanueva F.F. Physiology of growth hormone secretion and action. Endocr. Metab. Clin. 21: 483, 1992.

    CAS  Google Scholar 

  32. Ghigo E. Neurotransmitter control of growth hormone secretion. In: De la Cruz L.F. (Ed.). Regulation of growth hormone and somatic growth. Elsevier Science Publisher, Amsterdam 1992, p. 103.

    Google Scholar 

  33. Bowers C.Y. GH releasing peptides. Structure and kinetics. J. Pediatr. Endocrinol. 6: 21, 1992.

    Google Scholar 

  34. Van den Berghe G, de Zegher F., Bowers C.Y., Wouter P., Muller P., Soetens F., Vlasselaers D., Schetz M., Verwaest C., Lauwers P., Bouillon R. Pituitary responsiveness to GH-releasing peptide-2 and thyrotropin-releasing hormone in critical illness. Clin. Endocrinol. (Oxf.) 45: 341, 1996.

    Article  Google Scholar 

  35. Van den Berghe G, de Zegher F., Veldhuis J.D., Wouters P., Awoters M., Verbruggen W., Schetz M., Verwaest C., Lauwers P., Bouillon R., Bowers C.Y. The somatotropic axis in critical illness: Effect of continuous growth hormone (GH)-releasing hormone and GH-relasing peptide-2 infusion. J. Clin. Endocrinol. Metab. 82: 590, 1997.

    PubMed  Google Scholar 

  36. Masuda A., Shibasaki T., Hotta M., Suematsu H., Shizume K. Study on the mechanisms of abnormal growth hormone (GH) secretion in anorexia nervosa: no evidence of involvement of a low somatomedin-C level in the abnormal GH secretion. J. Endocrinol. Invest. 11: 297, 1988.

    Article  PubMed  CAS  Google Scholar 

  37. Tamai H.T., Komaki G., Matsubayashi S., Kobayashi N., Mori K., Nakagawa T., Truong M.P.M., Walter R.M., Kumagai L.F. Effect of cholinergic muscarinic receptor blockade on human growth hormone (GH)-releasing hormone (1–44)-induced GH secretion in anorexia nervosa. J. Clin. Endocrinol. Metab. 70: 738, 1990.

    Article  PubMed  CAS  Google Scholar 

  38. Rolla M., Andreoni A., Belliti D., Cristofani R., Ferdeghini M., Muller E.E. Blockade of cholinergic muscarinic receptors by pirenzepine and GHRH-induced GH secretion in the acute and recovery phase of anorexia nervosa and atypical eating disorders. Biol. Psych. 29: 1079, 1991.

    Article  CAS  Google Scholar 

  39. Clemmons D.R., Klibanski A., Underwood L.E., McArthur J.W., Ridgway E.C., Beitius I.Z., Van Wyk J.J. Reduction of plasma immunoreactive somatomedin C during fasting in humans. J. Clin. Endocrinol. Metab. 53: 1247, 1981.

    Article  PubMed  CAS  Google Scholar 

  40. Ho K.Y., Veldhuis J.D., Johnson M.L., Furlanetto R. Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion m man. J. Clin. Invest. 81: 968, 1988.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Hartman M.L., Veldhuis J.D., Johnson M.L., Lee M., Alberti K.G.M.M., Samojlik E., Thorner M.O. Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal man. J. Clin. Endocrinol. Metab. 74: 757, 1992.

    Article  PubMed  CAS  Google Scholar 

  42. Furlanetto R.W. Insulin-like growth factor measurements in the evaluation of growth hormone secretion. Horm. Res. 33(suppl 4): 25, 1990.

    Article  PubMed  CAS  Google Scholar 

  43. De Boer H., Block G.J., Poo-Snijders C., Van der Venn E.A. Diagnosis of growth hormone deficiency in adults. Lancet 343: 1645, 1994.

    Article  PubMed  Google Scholar 

  44. Bates A.S., Evans A.J., Jones I.P., Clayton R.N. 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. (Oxf.) 42: 425, 1995.

    Article  CAS  Google Scholar 

  45. 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.

    Article  PubMed  CAS  Google Scholar 

  46. Ghigo E., Arvat E., Gianotti L., Nicolosi M., Valetto M.R., Avagnina S., Bellitti D., Rolla M., Muller E.E., Camanni F. Arginine but not pyridostigmine, a Cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa. Biol. Psychol. 36: 689, 1994.

    Article  CAS  Google Scholar 

  47. Moller S., Becker U. Insulin-like growth factor-I and growth hormone in chronic liver disease. Dig. Dis. 10: 239, 1992.

    Article  PubMed  CAS  Google Scholar 

  48. Moller S., Juul A., Becker U., Flyvbjerg A., Skakkeback N.E., Henriksen J.H. Concentrations, release, and disposal of insulin-like growth factor (IGF)-binding proteins (IGFBP), IGF-I, and growth hormone in different vascular beds in patients with cirrhosis. J. Clin. Endocrinol. Metab. 80: 1148, 1995.

    PubMed  CAS  Google Scholar 

  49. Ross R.J.M., Chew S.L., Li L.D., Yateman M., Rodriguez-Arnao J., Holly J., Camacho-Hubner C. Expression of IGF-I and IGF-binding protein genes in cirrhotic liver. J. Endocrinol. 149: 209, 1996.

    Article  PubMed  CAS  Google Scholar 

  50. Friedman S.L. The cellular basis of hepatic fibrosis. N. Engl. J. Med. 328: 1828, 1993.

    Article  PubMed  CAS  Google Scholar 

  51. Hartman M.L., Faria A.C.S., Vance M.L., Johnson M.L., Thorner M.O., Veldhuis J.D. Temporal structure of in vivo growth hormone secretory events in humans. Am. J. Physiol. 260: E 101, 1991.

    CAS  Google Scholar 

  52. Voerman H.J., van Schijndey R.J.M., Groenevel A.B.J., de Boer H., Nauta J.P., Thijs L.G. Pulsatile hormone secretion during severe sepsis: accuracy of different blood sampling regimens. Metabolism 41: 934, 1992.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Divisione di Endocrinologia, Dipartimento di Medicina Interna, Università di Torino, C.so Dogliotti 14, 10126, Torino, Italia

    L. Gianotti, F. Broglio, G. Aimaretti, E. Arvat & E. Ghigo M.D.

  2. Divisione di Anestesiologia, Università di Milano, Milano, Italia

    S. Colombo & G. Gallioli

  3. Divisione di Cardiochirurgia, Università di Torino, Torino, Italia

    M. Di Summa & E. Sardo

  4. Divisione di Anestesiologia, Università di Padova, Padova, Italia

    G. Pittoni

  5. Dipartimento di Chirurgia Plastica, Centro Grandi Ustionati, Ospedale CTO, Torino, Italia

    M. Stella

  6. Divisione di Anestesiologia, Ospedale Bellaria, Bologna, Italia

    M. Zanello

  7. Pharmacia & Upjohn-Milano, Milano, Italy

    C. Miola

Authors
  1. L. Gianotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Broglio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Aimaretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Arvat
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Colombo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Di Summa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Gallioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. Pittoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. Sardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Stella
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M. Zanello
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. C. Miola
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. E. Ghigo M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gianotti, L., Broglio, F., Aimaretti, G. et al. Low IGF-I levels are often uncoupled with elevated GH levels in catabolic conditions. J Endocrinol Invest 21, 115–121 (1998). https://doi.org/10.1007/BF03350325

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03350325

Key-words

Search

Navigation