The activity of GH/IGF-I axis in anorexia nervosa and in obesity: A comparison with normal subjects and patients with hypopituitarism or critical illness

  • L. Gianotti
  • F. Broglio
  • J. Ramunni
  • F. Lanfranco
  • C. Gauna
  • A. Benso
  • M. Zanello
  • E. Arvat
  • E. Ghigo
Original Research Paper


GH/IGF-I axis activity changes have been reported both in anorexia nervosa (AN) and in obesity (OB). AN is characterized by GH hypersecretion and very low IGF-I levels as a result of undernutrition and acquired peripheral GH resistance. On the other hand OB is a GH hyposecretory state but IGF-I levels are generally preserved. The activity of GH/IGF-I axis in AN and OB has never been directly compared with that of other pathophysiological condi tions such as hypopituitarism and critical illness in which a reduction of both GH and IGFsecretion has been demonstrated. To this aim, we evaluated IGF-I levels and both basal and GHRH (1 μg/kg) IV-induced GH secretion in 20 female patients with anorexia nervosa (mean age: 19.1±0.8 years) and in 15 female and 5 male patients with simple obesity (mean age 39.0±3.0 years). We then compared the results with those of hypopituitaric patients with severe GH deficiency (GHD), including 10 female and 10 male patients (mean age: 32.0±2.1 years), and with 4 female and 7 male patients with critical illness (CRI) following multiple trau ma 72 hours after ICU admission (mean age: 59.2±1.2 years). Twenty-six normal subjects (NS including 14 female and 12 male patients (mean age: 37.8±3.7 years) were studied as controls Basal IGF-I levels in AN patients (93.5±11 μg/L) were lower (p<0.001) than in the NS (201.7±13.5 μg/L) and OB (194.5±28.6 μg/L), which, in turn, were similar. IGF-I levels in AN patients were lower than in CRI patients (162.8±17.4 μg/L) and higher than in GHD patients (76.7±13.5 μg/L) but these differences did not attain statistical significance. Basal GH levels in AN patients (7.6±2.5 μg/L) were higher (p<0.001) than in NS (1.8±0.3 μg/L), OB patients (1.1±0.5 μg/L), CRI patients (1.8±0.5 μg/L) and GHD patients (0.3±0.1 μg/L), which were the lowest (p<0.01). The GHRH-induced GH rise in AN patients (AUC: 2032.9±253.5 μg/L/h) was three fold higher (p<0.001) than in NS (662.1±80.3 μg/L). On the other hand in OB (332.4±74.7 μg/L/h) the GH response to GHRH was similar to that in CRI (199.6±98.8 μg/L/h); both were clearly higher (p<0.01) than in GHD patients (25.1±5.2 μg/L/h) but lower (p<0.01) than in NS These findings demonstrate that in AN patients, in spite of a clear increase of both basal and GHRH-induced GH secretion, IGF-I synthesis and release are as markedly impaired as in patients with panhypopituitarism and severe GHD. On the other hand in OB and in CRI, IGFsynthesis and release are preserved despite marked impairment to GHRH-induced GH secre tion. These results reinforce the major role of nutrition in conditioning the activity of GH/IGFaxis in different patho-physiological states.

Key words

Growth hormone IGF-I GHRH eating disorders catabolism critical illness 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ross R.J.M., Chew S.L.: Acquired growth hormone resistance. Eur. J. Endocrinol., 132, 655–660, 1995.PubMedCrossRefGoogle Scholar
  2. 2.
    Phillips L.S., Unterman T.G.: Somatomedin activity in disorders of nutrition and metabolism. Clin. Endocrinol. Metab., 13, 145–180, 1995.CrossRefGoogle Scholar
  3. 3.
    Donaghy A.J., Baxter R.C.: Insulin-like growth factor bioactivity and its modification in growth hormone resistant states. In: Ross R.J.M., Savage M.O. (Eds.), Bailliere’s Clinical Endocrinology and Metabolism, Growth hormone resistance. London, WB Saunders, 1996, p. 421–447.Google Scholar
  4. 4.
    Berelowitz M., Szabo M., Frohman L.A., Firestone S., Chu L.: Somatomedin C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science, 212, 1279–1281, 1981.PubMedCrossRefGoogle Scholar
  5. 5.
    Ceda G.P.: IGFs in the feedback control of GH secretion: hypothalamic and/or pituitary action? J. Endocrinol. Invest., 18, 734–737, 1995.PubMedGoogle Scholar
  6. 6.
    Tamai H.T., Komaki G., Matsubayashi S., Kobayashi N., Mori K., Nakagawa T., Truong M.P., Walter R.M. jr., 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, 738–741, 1990.PubMedCrossRefGoogle Scholar
  7. 7.
    Rolla M., Andreoni A., Belliti D., Cristofani R., Federghini M., Muller E.E.: Blockade of cholinergic muscarinic receptors by pirenzepine and GHRH-induced GH secretion in the acute and recovery phase of anorexia and atypical eating disorders. Biol. Psychiatry, 29, 1079–1091, 1991.PubMedCrossRefGoogle Scholar
  8. 8.
    Ghigo E., Arvat E., Gianotti L., Nicolosi M., Valetto M.R., Avagnina S., Bellitti D., Rolla D., Muller E.E., Camanni F.: Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa. Biol. Psychiatry, 36, 689–695, 1994.PubMedCrossRefGoogle Scholar
  9. 9.
    Gianotti L., Arvat E., Valetto M.R., Ramunni J., Di Vito L., Maccagno B., Camanni F., Ghigo E.: Effects of beta-adrenergic agonists and antagonists on the GH response to GHRH in anorexia nervosa. Biol. Psychiatry, 43, 181–187, 1998.PubMedCrossRefGoogle Scholar
  10. 10.
    Glass A.R.: Endocrine aspects of obesity. Med. Clin. North Am., 73, 139–160, 1989.PubMedGoogle Scholar
  11. 11.
    Veldhuis J.D., Iranmanesh A., Ho K.K.Y., Waters M.J., Johnson M.L., Lizarralde G.: Dual effects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J. Clin. Endocrinol. Metab., 72, 51–59, 1991.PubMedCrossRefGoogle Scholar
  12. 12.
    Hochberg Z., Hertz P., Colin V., Ish-shalom S., Yeshurun D., Youdim M.B.H., amit T.: The distal axis of growth hormone (GH) in nutritional disorder: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa. Metabolism, 41, 106–112, 1992.PubMedCrossRefGoogle Scholar
  13. 13.
    Caufriez A., Golstein J., Lebrun P., Herchuelz A., Furlanetto R., Copinschi G.: Relations between immunoreactive somatomedin C, insulin and T3 patterns during fasting in obese subjects. Clin. Endocrinol., 20, 65–70, 1984.CrossRefGoogle Scholar
  14. 14.
    Rassmussen M.H., Frystyk J., Andersen T., Breum L., Christiansen J.S., Hilsted J.: The impact of obesity, fat distribution and energy restriction on insulin-like growth factor I (IGFI), IGF-binding protein-3, insulin and growth hormone. Metabolism, 43, 315–319, 1994.CrossRefGoogle Scholar
  15. 15.
    Copeland K.C., Colletti R.B., Devlin J.T., McAuliffe T.L.: The relationship between insulin-like growth factor I, adiposity, and aging. Metabolism, 39, 584–587, 1990.PubMedCrossRefGoogle Scholar
  16. 16.
    Maccario M., Valetto M.R., Savio P., Aimaretti G., Baffoni C., Procopio M., Grottoli S., Oleandri S.E., Arvat E., Ghigo E.: Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency. Int. J. Obes., 21, 27–32, 1997.CrossRefGoogle Scholar
  17. 17.
    Tannenbaum G.S., Lapointe M., Gurd W., Finkelstein J.A.: Mechanisms of impaired growth hormone secretion in genetically obese Zucker rats: roles of growth hormone-releasing factor and somatostatin. Endocrinology, 127, 3087–3095, 1990.PubMedCrossRefGoogle Scholar
  18. 18.
    Taylor L.M., Blackard W.G.: Effects of lipids on growth hormone synthesis by isolated pituitaries. Proceedings of the Society for Experimental Biology & Medicine, 73, 765–770, 1971.Google Scholar
  19. 19.
    Renier G., Abribat T., Brazeau P., Deslauriers P., Gradeau P.: Cellular mechanism of caprylic acid-induced growth hormone suppression. Metabolism, 39, 1108–1112, 1990.PubMedCrossRefGoogle Scholar
  20. 20.
    Thissen J.P., Ketelslegers J.M., Underwood L.E.: Nutritional regulation of the insulin-like growth factors. Endocr. Rev., 15, 80–101, 1994.PubMedGoogle Scholar
  21. 21.
    Froesch E.R., Guler H.P., Schmid C., Bink K., Zapf J.: Therapeutic potential of insulinlike growth factor I. Trends Endocrinol. Metab., 1, 254–260, 1990.PubMedCrossRefGoogle Scholar
  22. 22.
    Underwood L.E., Van Wyk J.J.: Normal and aberrant growth. In: Wilson J.D., Foster D.W. (Eds.), Williams Textbook of Endocrinology, ed. 8. Philadelphia, Saunders Co, 1992, p. 1079.Google Scholar
  23. 23.
    Cuneo R.C., Salomon F., Mc Gauley G.A., Sonksen P.H.: The growth hormone deficiency syndrome in adults. Clin. Endocrinol., 37, 387–397, 1992.CrossRefGoogle Scholar
  24. 24.
    Van den Berghe G., de Zegher F., Lauwers P.: Growth hormone secretion in critical illness: effects of dopamine. J. Clin. Endocrinol. Metab., 79, 1141–1146, 1994.PubMedGoogle Scholar
  25. 25.
    Melarvie S., Jeevanandam M., Holaday N.J., Petersen S.R.: Pulsatile nature of growth hormone levels in critical ill trauma victims. Surgery, 117, 402–408, 1995.PubMedCrossRefGoogle Scholar
  26. 26.
    Wilmore D.W.: Catabolic illness. Strategies for enhancing recovery. N. Engl. J. Med., 325, 695–702, 1991.PubMedCrossRefGoogle Scholar
  27. 27.
    Sassolas G.: Potential therapeutic applications of growth hormone in adults. Horm. Res., 42, 72–78, 1994.PubMedCrossRefGoogle Scholar
  28. 28.
    Voerman B.J., Strack van Schijndel R.J.M., Groeneveld A.B.J., de Boer H., Nauta J.P., Thijs L.G.: Recombinant human growth hormone in critically ill nonseptic patients: results from a randomized, placebo-controlled trial. Crit. Care Med., 23, 665–672, 1995.PubMedCrossRefGoogle Scholar
  29. 29.
    Pichard C., Kyle U., Chevrolet J.C., Jolliet P., Slosman D., Mensi N., Temler E., Ricou B.: Lack of effects of recombinant growth hormone on muscle function in patients requiring prolonged mechanical ventilation: a prospective, randomized, controlled study. Crit. Care Med., 6, 403–413, 1996.CrossRefGoogle Scholar
  30. 30.
    Phillips L.S., Young H.S.: Nutrition and somatomedin I. Effect of fasting and refeeding on serum somatomedin activity and cartilage growth activity in rats. Endocrinology, 99, 304–310, 1976.PubMedCrossRefGoogle Scholar
  31. 31.
    Merimee T.J., Fineberg S.E.: Dietary regulation of human growth hormone secretion. Metabolism, 22, 1491–1497, 1973.PubMedCrossRefGoogle Scholar
  32. 32.
    Clemmons D.R., Klibanski A., Underwood L.E., Mc Arthur 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, 1247–1250, 1981.PubMedCrossRefGoogle Scholar
  33. 33.
    Jones J.I., Clemmons D.R.: Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev., 16, 3–34, 1995.PubMedGoogle Scholar
  34. 34.
    Clemmons D.R., Underwood L.E.: Nutritional regulation of IGF-I and IGF binding proteins. Annu. Rev. Nutr., 11, 393–412, 1991.PubMedCrossRefGoogle Scholar
  35. 35.
    Houston B., O’Neill I.E.: Insulin and growth hormone act sinergistically to stimulate insulin-like growth factor-I production by cultured chicken hepatocytes. J. Endocrinol., 128, 389–393, 1991.PubMedCrossRefGoogle Scholar
  36. 36.
    Clemmons D.R., Van Wyk J.J.: Factors controlling blood concentration of somatomedin C. Clin. Endocrinol. Metab., 13, 113–143, 1984.CrossRefGoogle Scholar
  37. 37.
    Ghigo E., Aimaretti G., Gianotti L., Bellone J., Arvat M., Camanni F.: New approach to the diagnosis of growth hormone deficiency in adults. Eur. J. Endocrinol., 134, 352–356, 1996.PubMedCrossRefGoogle Scholar
  38. 38.
    Muller E.E., Brambilla F.: Disordini del comportamento alimentare. Anoressia e bulimia nervosa. Roma-Milano, Pythagora Press, 1990.Google Scholar
  39. 39.
    Maccario M., Procopio M., Grottoli S., Oleandri S.E., Boffano G.M., Taliano M., Camanni F., Ghigo E.: Effects of Acipimox, an antilipolytic drug, on the growth hormone (GH) response to GH-releasing hormone alone or combined with arginine in obesity. Metabolism, 45, 1–6, 1996.CrossRefGoogle Scholar
  40. 40.
    Van den Berghe G., de Zegher F., Veldhuis J.D., Wouters P., Awouters M., Verbruggen W., Schetz M., Verwaest C., Lauwers P., Bouillon R., Bowers C.Y.: The somatotropic axis in critical illness: effect of continous growth hormone (GH)-releasing hormone and GH-relasing peptide-2 infusion. J. Clin. Endocrinol. Metab., 82, 590–595, 1997.PubMedGoogle Scholar
  41. 41.
    Gianotti L., Broglio F., Arvat E., Pittoni G., Gallioli G., Zanello M., Colombo S., Marian F., Picarone M., Minuto F., Papini M.G., Boghen M.F., Miola C., Ghigo E.: GH/IGF-I axis in catabolic patients with sepsis or trauma. 79th Annual Meeting of The Endocrine Society, Minneapolis June 11-14 1997, Abs P1-109.Google Scholar
  42. 42.
    Dieguez C., Page M.D., Scanlon M.F.: Growth regulation and its alteration in disease states. Clin. Endocrinol., 28, 109–143, 1988.Google Scholar
  43. 43.
    Jenkins R.C., Ross R.J.M.: The Endocrinology of the critically ill. Curr. Opin. Endocrinol. Diab., 3, 138–145, 1996.CrossRefGoogle Scholar
  44. 44.
    Imura H., Fukata J., Mori T.: Cytokines and endocrine function: an interaction between the immune and neuroendocrine systems. Clin. Endocrinol., 35, 107–115, 1991.CrossRefGoogle Scholar

Copyright information

© Editrice Kurtis 1998

Authors and Affiliations

  • L. Gianotti
    • 1
  • F. Broglio
    • 1
  • J. Ramunni
    • 1
  • F. Lanfranco
    • 1
  • C. Gauna
    • 1
  • A. Benso
    • 1
  • M. Zanello
    • 2
  • E. Arvat
    • 1
  • E. Ghigo
    • 1
  1. 1.Division of Endocrinology, Department of Internal MedicineUniversity of TorinoTorinoItaly
  2. 2.Intensive Care UnitBellaria HospitalBolognaItaly

Personalised recommendations