Drugs

, Volume 49, Issue 5, pp 656–663 | Cite as

Growth Hormone Replacement Therapy for Growth Hormone—Deficient Adults

  • Jake K. Powrie
  • Andrew Weissberger
  • Peter Sönksen
Review Article

Summary

Recent research has confirmed previous clinical suspicion that adults with pituitary disease and growth hormone (GH) deficiency have impaired physical and psychological performance even in the presence of adequate adrenal, thyroid and gonadal hormone replacement therapy. This GH deficiency syndrome is characterised particularly by impaired psychological well-being, abnormal body composition with increased abdominal adiposity, reduced strength and exercise capacity, reduced basal metabolic rate, reduced bone density and an elevation in total and low density lipoprotein cholesterol. This latter finding may be important in the context of the observed increase in cardiovascular mortality rates of GH-deficient adults. GH replacement therapy administered as a once-daily subcutaneous injection can restore a near normal quality of life to many of these patients, although there is as yet no evidence that this treatment reduces mortality. Adverse effects of GH therapy are few and have probably been overstated due to excessive doses used in the initial studies. These can be minimised by starting at a low initial dose and increasing gradually while monitoring clinical response and serum insulin-like growth factor-1 values. All adults with GH deficiency should now be considered for GH replacement therapy.

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References

  1. 1.
    Salomon F, Cuneo RC, Hesp R, et al. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 1989; 321: 1797–803PubMedCrossRefGoogle Scholar
  2. 2.
    Whitehead HM, Boreham C, McIlrath EM, et al. Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study. Clin Endocrinol 1992; 36: 45–52CrossRefGoogle Scholar
  3. 3.
    Bengtsson B-A, Eden S, Lönn L, et al. Treatment of adults with growth hormone (GH) deficiency with recombinant human growth hormone. J Clin Endocrinol Metab 1993; 76: 309–17PubMedCrossRefGoogle Scholar
  4. 4.
    Jørgensen JOL, Pedersen SA, Thuesen L, et al. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989; 1: 1221–5PubMedCrossRefGoogle Scholar
  5. 5.
    Binnerts A, Swart GR, Wilson JHP, et al. The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol 1992; 37: 79–87CrossRefGoogle Scholar
  6. 6.
    Rosen T, Bosaeus I, Tölli J, et al. Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency. Clin Endocrinol 1993; 38: 63–71CrossRefGoogle Scholar
  7. 7.
    Cuneo RC, Salomon F, Wiles CM, et al. Skeletal muscle performance in adults with growth hormone deficiency. Horm Res 1990; 33: 55–60PubMedCrossRefGoogle Scholar
  8. 8.
    Cuneo RC, Salomon F, Wiles CM, et al. Growth hormone treatment in growth hormone-deficient adults: I. Effects on muscle mass and strength. J Appl Physiol 1991; 70: 688–94PubMedGoogle Scholar
  9. 9.
    Russell-Jones DL, Weissberger AJ, Bowes SB, et al. The effects of growth hormone on protein metabolism in adult growth hormone deficient patients. Clin Endocrinol 1993; 38: 427–31CrossRefGoogle Scholar
  10. 10.
    Henneman PH, Forbes AP, Moldawer M, et al. Effects of human growth hormone in man. J Clin Invest 1960; 39: 1223–38PubMedCrossRefGoogle Scholar
  11. 11.
    Rudman D, Chyatte SB, Patterson JH, et al. Observations of the responsiveness of human subjects to human growth hormone: effects of endogenous growth hormone deficiency and myotonic dystrophy. J Clin Invest 1971; 50: 1941–9PubMedCrossRefGoogle Scholar
  12. 12.
    Ikkos D, Luft R, Gemzell CA. The effect of human growth hormone in man. Acta Endocrinol 1959; 32: 341–61PubMedGoogle Scholar
  13. 13.
    Parra A, Argote RM, Garcia G, et al. Body composition in hypopituitary dwarfs before and during growth hormone therapy. Metabolism 1979; 28: 851–7PubMedCrossRefGoogle Scholar
  14. 14.
    Cuneo RC, Salomon F, Wilmshurst P, et al. Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system. Clin Sci 1991; 81: 587–92PubMedGoogle Scholar
  15. 15.
    Ho KKY, Weissberger AJ. The antinatriuretic action of biosynthetic human growth hormone in man involves activation of the renin-angiotensin system. Metabolism 1990; 39: 133–7PubMedCrossRefGoogle Scholar
  16. 16.
    Caidahl K, Eden S, Bengtsson B-A. Cardiovascular and renal effects of growth hormone. Clin Endocrinol 1994; 40: 393–400CrossRefGoogle Scholar
  17. 17.
    Cuneo RC, Wilmshurst P, Lowy C, et al. Cardiac failure responding to growth hormone. Lancet 1989; 1: 838–9PubMedCrossRefGoogle Scholar
  18. 18.
    Frustaci A, Perrone GA, Gentiloni N, et al. Reversible dilated cardiomyopathy due to growth hormone deficiency. Am J Clin Pathol 1992; 97: 503–11PubMedGoogle Scholar
  19. 19.
    Jørgensen JOL, Pedersen SA, Laurberg P, et al. Effects of growth hormone therapy on thyroid function of growth hormone—deficient adults with and without concomitant thyroxine-substituted central hypothyroidism. J Clin Endocrinol Metab 1989; 69: 1127–32PubMedCrossRefGoogle Scholar
  20. 20.
    Cuneo RC, Salomon F, Watts GF, et al. Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism 1993; 42: 1519–23PubMedCrossRefGoogle Scholar
  21. 21.
    Libber SM, Plotnick LP, Johanson AJ, et al. Long-term follow-up of hypopituitary patients treated with human growth hormone. Medicine 1990; 69: 46–55PubMedCrossRefGoogle Scholar
  22. 22.
    Rosen T, Bengtsson B-A. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990; 336: 285–8PubMedCrossRefGoogle Scholar
  23. 23.
    Shore RM, Chesney RW, Mazess RB, et al. Bone mineral status in growth hormone deficiency. J Pediatr 1980; 96: 393–6PubMedCrossRefGoogle Scholar
  24. 24.
    Kaufman J-M, Taelman P, Vermeulen A, et al. Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab 1992; 74: 118–23PubMedCrossRefGoogle Scholar
  25. 25.
    Johansson AG, Burman P, Westermark K, et al. The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor 1. J Intern Med 1992; 232: 447–52PubMedCrossRefGoogle Scholar
  26. 26.
    Holmes SJ, Economou G, Whitehouse RW, et al. Reduced bone mineral density in patients with adult onset growth hormone deficiency. J Clin Endocrinol Metab 1994; 78: 669–74PubMedCrossRefGoogle Scholar
  27. 27.
    Beshyah SA, Thomas E, Kyd P, et al. The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism. Clin Endocrinol 1994; 40: 383–91CrossRefGoogle Scholar
  28. 28.
    Burnstein S, Chen I-W, Tsang RC. Effects of growth hormone replacement on 1, 25-dihydroxyvitamin D and calcium metabolism. J Clin Endocrinol 1983; 56: 1246–51CrossRefGoogle Scholar
  29. 29.
    Caverzasio J, Montessuit CH, Bonjour JP. Stimulatory effects of recombinant human IGF-1 on renal Pitransport and plasma 1, 25-dihydroxyvitamin D3. In: Cohn DV, Glorieux FH, Martin TJ, editors. Calcium regulation and bone metabolism. Amsterdam: Elsevier, 1990: 137–9Google Scholar
  30. 30.
    O’Halloran DJ, Tsatsoulis A, Whitehouse RW, et al. Increased bone density after recombinant human growth hormone (GH) therapy in adults with isolated GH deficiency. J Clin Endocrinol Metab 1993; 76: 1344–8PubMedCrossRefGoogle Scholar
  31. 31.
    Degerblad M, Elgindy N, Hall K, et al. Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism. Acta Endocrinol 1992; 126: 387–93PubMedGoogle Scholar
  32. 32.
    Black MM, Shuster S, Bottoms E. Skin collagen and thickness in acromegaly and hypopituitarism. Clin Endocrinol 1972; 1: 259–63CrossRefGoogle Scholar
  33. 33.
    Jensen LT, Jørgensen JOL, Risteli J, et al. Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH. Acta Endocrinol 1991; 124: 278–82PubMedGoogle Scholar
  34. 34.
    Rudman D, Feller AG, Nagraj HS, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990; 323: 1–6PubMedCrossRefGoogle Scholar
  35. 35.
    Cuneo RC, Salomon F, Wiles CM, et al. Growth hormone treatment in growth hormone-deficient adults: II. Effects on exercise performance. J Appl Physiol 1991; 70: 695–700Google Scholar
  36. 36.
    Jørgensen JOL, Pedersen SA, Thuesen L, et al. Long-term growth hormone treatment in growth hormone deficient adults. Acta Endocrinol 1991; 125: 449–53PubMedGoogle Scholar
  37. 37.
    Whitehead HM, Gilliland JS, Allen IV, et al. Growth hormone treatment in adults with growth hormone deficiency: effect on muscle fibre size and proportions. Acta Paediatr Scand 1989; 356 Suppl.: 65–7CrossRefGoogle Scholar
  38. 38.
    McGauley GA, Cuneo RC, Salomon F, et al. Psychological well-being before and after growth hormone treatment in adults with growth hormone deficiency. Horm Res 1990; 33 Suppl. 4: 52–4PubMedCrossRefGoogle Scholar
  39. 39.
    Cuneo RC, Salomon F, McGauley GA, et al. The growth hormone deficiency syndrome in adults. Clin Endocrinol 1992; 37: 387–97CrossRefGoogle Scholar
  40. 40.
    Hoffman DM, O’Sullivan AJ, Baxter RC, et al. Diagnosis of growth hormone deficiency in adults. Lancet 1994; 343: 1064–8PubMedCrossRefGoogle Scholar
  41. 41.
    Sönksen PH, Verikou K, Weissberger AJ. The diagnosis of growth hormone deficiency in adulthood. Endocrinol Metab 1994; 1 Suppl. B: 25Google Scholar
  42. 42.
    Muggeo M, Fedele D, Tiengo A, et al. Human growth hormone and cortisol response to insulin stimulation in ageing. J Gerontol 1975; 30: 546–51PubMedGoogle Scholar
  43. 43.
    Rudman D, Kutner MH, Rogers CM, et al. Impaired growth hormone secretion in the adults population: relation to age and adiposity. J Clin Invest 1981; 67: 1361–9PubMedCrossRefGoogle Scholar
  44. 44.
    Iranmanesh A, Lizarralde G, Veldhuis JD. Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 1991; 73: 1081–8PubMedCrossRefGoogle Scholar
  45. 45.
    Malozowski S, Tanner LA, Wysowski D, et al. Growth hormone, insulin-like growth factor I, and benign intracranial hypertension. N Engl J Med 1993; 329: 665–6PubMedCrossRefGoogle Scholar
  46. 46.
    Cohn L, Feller AG, Draper MW, et al. Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-1 concentrations. Clin Endocrinol 1993; 39: 417–25CrossRefGoogle Scholar
  47. 47.
    Holloway L, Butterfield G, Hintz RL, et al. Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women. J Clin Endocrinol Metab 1994; 79: 470–9PubMedCrossRefGoogle Scholar
  48. 48.
    British National Formulary, No. 28. British Medical Association and the Royal Pharmaceutical Society of Great Britain, 1994: 296Google Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Jake K. Powrie
    • 1
  • Andrew Weissberger
    • 1
  • Peter Sönksen
    • 1
  1. 1.Division of Medicine, 4th Floor, North Wing, United Medical and Dental Schools of Guy’s and St Thomas’St Thomas’ HospitalLondonEngland

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