Growth Hormone pp 281-290 | Cite as

Dose Titration and Monitoring GH Treatment in the Adult

  • S J Howell
  • A Rahim
  • S M Shalet
Part of the Endocrine Updates book series (ENDO, volume 4)

Abstract

Increasingly, growth hormone (GH) replacement is being offered to adults with severe GH deficiency (GHD). Initial reports of the benefits of GH therapy (23, 35) in the adult GHD population were based on trials using doses of GH comparable to those which had been used for years in paediatric practice. Whilst most studies demonstrated benefits of GH therapy, two observations suggested that in adults these doses were supraphysiological. Firstly, compared with children, the incidence of side effects in adults was greater and often responded to a dose reduction. Salomon et al (35) reported side effects of fluid retention, arthralgia or myalgia in more than half of the patients they treated with 0.07 IU/kg/day of GH. Furthermore a review by De Boer (10) of several studies published between 1989 and 1993 demonstrated that 61% of patients treated with GH at a dose of above 2.5 IU/ m2/day reported side effects. Secondly a proportion of patients had IGF-1 levels above the normal range suggesting over-treatment. In 1993 Moller et al (27) demonstrated a dose-dependent rise in IGF-1 levels during treatment of GHD adults, with markedly elevated levels following 4 IU/ m2/day of GH. More recent studies have confirmed raised IGF-1 levels in patients receiving high dose GH replacement (8,11,27).

Keywords

Cholesterol Obesity Carbohydrate Titration Adenoma 

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References

  1. 1.
    Al-Shoumer-KA; Page-B; Thomas-E; Murphy-M; Beshyah-SA; Johnston-DG. Effects of four years’ treatment with biosynthetic human growth hormone (GH) on body composition in GH-deficient hypopituitary adults. Eur-J-Endocrinol. 1996; 135(5): 559–567.PubMedCrossRefGoogle Scholar
  2. 2.
    Amato-G; Carella-C; Fazio-S; La-Montagna-G; Cittadini-A; Sabatini-D; Marciano-Mone-C; Sacca-L; Bellastella-A. Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses. J-Clin-Endocrinol-Metab. 1993; 77(6): 1671–1676.PubMedCrossRefGoogle Scholar
  3. 3.
    Attanasio-AF; Lamberts-SW; Matranga-AM; Birkett-MA; Bates-PC; Valk-NK; Hilsted-J; Bengtsson-BA; Strasburger-CJ. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group. J-Clin-Endocrinol-Metab. 1997; 82(1): 82–88.PubMedCrossRefGoogle Scholar
  4. 4.
    Baum-HB; Biller-BM; Finkelstein-JS; Cannistraro-KB; Oppenhein-DS; Schoenfeld-DA; Michel-TH; Wittink-H; Klibanski-A. Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial. Ann-Intern-Med. 1996; 125(11): 883–890.PubMedGoogle Scholar
  5. 5.
    Bengtsson-BA; Eden-S; Lonn-L; Kvist-H; Stokland-A; Lindstedt-G; Bosaeus-I; Tolli-J; Sjostrom-L; Isaksson-OG. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J-Clin-Endocrinol-Metab. 1993; 76(2): 309–317.PubMedCrossRefGoogle Scholar
  6. 6.
    Binnerts-A; Swart-GR; Wilson-JH; Hoogerbrugge-N; Pols-HA; Birkenhager-JC; Lamberts-SW. 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-Oxf. 1992; 37(1): 79–87.PubMedCrossRefGoogle Scholar
  7. 7.
    Burman-P; Broman-JE; Hetta-J; Wiklund-I; Erfurth-EM; Hagg-E; Karlsson-FA. Quality of life in adults with growth hormone (GH) deficiency: response to treatment with recombinant human GH in a placebo-controlled 21-month trial. J-Clin-Endocrinol-Metab. 1995; 80(12): 3585–3590.PubMedCrossRefGoogle Scholar
  8. 8.
    Chipman-JJ, Attanasio-AF, Birkett-MA, Bates-PC, Webb-S, Lamberts-SWJ. The safety profile of GH replacement therapy in adults. Clin-Endocrinol-Oxf. 1997; 46 (4): 473–481.PubMedCrossRefGoogle Scholar
  9. 9.
    De-Boer-H; Blok-GJ; Voerman-HJ; De-Vries-PM; Van-der-Veen-EA. Body composition in adult growth hormone-deficient men, assessed by anthropometry and bioimpedance analysis. J-Clin-Endocrinol-Metab. 1992, 75(3): 833–837.PubMedCrossRefGoogle Scholar
  10. 10.
    De Boer-H, Blok-GJ, Van Der Veen-EA. Clinical aspects of growth hormone deficiency in adults. Endocrine Reviews. 1995; 16 (1), 63–86.PubMedCrossRefGoogle Scholar
  11. 11.
    De-Boer-H; Blok-GJ; Voerman-B; de-Vries-P; Popp-Snijders-C; van-der-Veen-E. The optimal growth hormone replacement dose in adults, derived from bioimpedance analysis. J-Clin-Endocrinol-Metab. 1995; 80(7): 2069–2076.PubMedCrossRefGoogle Scholar
  12. 12.
    De-Boer-H; Blok-GJ; Popp-Snijders-C; Stuurman-L; Baxter-RC; van-der-Veen-E. Monitoring of growth hormone replacement therapy in adults, based on measurement of serum markers. J-Clin-Endocrinol-Metab. 1996; 81(4): 1371–1377.PubMedCrossRefGoogle Scholar
  13. 13.
    De-Boer-H; Blok-GJ; Voerman-B; Derriks-P; van-der-Veen-E. Changes in subcutaneous and visceral fat mass during growth hormone replacement therapy in adult men. Int-J-Obes-Relat-Metab-Disord. 1996; 20(6): 580–587.PubMedGoogle Scholar
  14. 14.
    Finkelstein-JW; Roffwarg-HP; Boyar-RM; Kream-J; Hellman-L. Age-related change in the twenty-four-hour spontaneous secretion of growth hormone. J-Clin-Endocrinol-Metab. 1972 Nov; 35(5): 665–670PubMedCrossRefGoogle Scholar
  15. 15.
    Fowelin-J; Attvall-S; Lager-I; Bengtsson-BA. Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency. Metabolism. 1993; 42(11): 1443–1447.PubMedCrossRefGoogle Scholar
  16. 16.
    Garry-P; Collins-P; Devlin-JG. An open 36-month study of lipid changes with growth hormone in adults: lipid changes following replacement of growth hormone in adult acquired growth hormone deficiency. Eur-J-Endocrinol. 1996; 134(1): 61–66.PubMedCrossRefGoogle Scholar
  17. 17.
    Hansen-TB; Brixen-K; Vahl-N; Jorgensen-JO; Christiansen-JS; Mosekilde-L; Hagen-C. Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study. J-Clin-Endocrinol-Metab. 1996; 81(9): 3352–3359.PubMedCrossRefGoogle Scholar
  18. 18.
    Hoffman-DM; O’Sullivan-AJ; Baxter-RC; Ho-KK. Diagnosis of growthhormone deficiency in adults. Garvan Institute of Medical Research, St Vincent’s Hospital, Sydney, NSW, Australia. Lancet. 1994; 343(8905): 1064–1068.PubMedCrossRefGoogle Scholar
  19. 19.
    Holmes-SJ. Growth hormone replacement in adults with growth hormone deficiency. MD thesis-University of London. 1995.Google Scholar
  20. 20.
    Holmes-SJ; Shalet-SM. Which adults develop side-effects of growth hormone replacement? Clin-Endocrinol-Oxf. 1995 Aug; 43(2): 143–149PubMedCrossRefGoogle Scholar
  21. 21.
    Johannsson-G; Bjarnason-R; Bramnert-M; Carlsson-LM; Degerblad-M; Manhem-P; Rosen-T; Thoren-M; Bengtsson-BA. The individual responsiveness to growth hormone (GH) treatment in GH-deficient adults is dependent on the level of GH-binding protein, body mass index, age, and gender. J-Clin-Endocrinol-Metab. 1996; 81(4): 1575–1581.PubMedCrossRefGoogle Scholar
  22. 22.
    Johannsson-G; Rosen-T; Bosaeus-I; Sjostrom-L; Bengtsson-BA. Two years of growth hormone (GH) treatment increases bone mineral content and density in hypopituitary patients with adult-onset GH deficiency. J-Clin-Endocrinol-Metab. 1996; 81(8): 2865–2873.PubMedCrossRefGoogle Scholar
  23. 23.
    Jorgensen-JO; Pedersen-SA; Thuesen-L; Jorgensen-J; Ingemann-Hansen-T; Skakkebaek-NE; Christiansen-JS. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet. 1989; 1(8649): 1221–1225.PubMedCrossRefGoogle Scholar
  24. 24.
    Jorgensen-JO; Thuesen-L; Muller-J; Ovesen-P; Skakkebaek-NE; Christiansen-JS. Three years of growth hormone treatment in growth hormone-deficient adults: near normalization of body composition and physical performance. Eur-J-Endocrinol. 1994; 130(3): 224–228.PubMedCrossRefGoogle Scholar
  25. 25.
    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. Iranmanesh-A; J-Clin-Endocrinol-Metab. 1991 Nov; 73(5): 1081–1088.PubMedCrossRefGoogle Scholar
  26. 26.
    McGauley-GA. Quality of life assessment before and after growth hormone treatment in adults with growth hormone deficiency. Acta-Paediatr-Scand-Suppl. 1989;356:70–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Moller-J; Jorgensen-JO; Lauersen-T; Frystyk-J; Naeraa-RW; Orskov-H; Christiansen-JS. Growth hormone dose regimens in adult GH deficiency: effects on biochemical growth markers and metabolic parameters. Clin-Endocrinol-Oxf. 1993; 39(4): 403–408.PubMedCrossRefGoogle Scholar
  28. 28.
    Ogilvy-Stuart-AL; Ryder-WD; Gattamaneni-HR; Clayton-PE; Shalet-SM. Growth hormone and tumour recurrence. BMJ. 1992; 304(6842): 1601–1605.PubMedCrossRefGoogle Scholar
  29. 29.
    O’Halloran-DJ; Tsatsoulis-A; Whitehouse-RW; Holmes-SJ; Adams-JE; Shalet-SM. Increased bone density after recombinant human growth hormone (GH) therapy in adults with isolated GH deficiency. J-Clin-Endocrinol-Metab. 1993; 76(5): 1344–1348.PubMedCrossRefGoogle Scholar
  30. 30.
    Orme-SM; Sebastian-JP; Oldroyd-B; Stewart-SP; Grant-PJ; Stickland-MH; Smith-MA; Belchetz-PE. Comparison of measures of body composition in a trial of low dose growth hormone replacement therapy. Clin-Endocrinol-Oxf. 1992; 37(5): 453–459.PubMedCrossRefGoogle Scholar
  31. 31.
    Rodriguez-Arnao-J; Perry-L; Besser-GM; Ross-RJ. Growth hormone treatment in hypopituitary GH deficient adults reduces circulating cortisol levels during hydrocortisone replacement therapy. Clin-Endocrinol-Oxf. 1996 Jul; 45(1): 33–37PubMedCrossRefGoogle Scholar
  32. 32.
    Ron-E; Gridley-G; Hrubec-Z; Page-W; Arora-S; Fraumeni-JF Jr. Acromegaly and gastrointestinal cancer. Cancer. 1991; 68(8): 1673–1677PubMedCrossRefGoogle Scholar
  33. 33.
    Rosen-T; Bosaeus-I; Tolli-J; Lindstedt-G; Bengtsson-BA. Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency. Clin-Endocrinol-Oxf. 1993 38(1): 63–71.PubMedCrossRefGoogle Scholar
  34. 34.
    Russell-Jones-DL; Watts-GF; Weissberger-A; Naoumova-R; Myers-J; Thompson-GR; Sonksen-PH. The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients. Clin-Endocrinol-Oxf. 1994; 41(3): 345–350.PubMedCrossRefGoogle Scholar
  35. 35.
    Salomon-F; Cuneo-RC; Hesp-R; Sonksen-PH. 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(26): 1797–1803PubMedCrossRefGoogle Scholar
  36. 36.
    Sartorio-A; Ortolani-S; Conti-A; Cherubini-R; Galbiati-E; Faglia-G. Effects of recombinant growth hormone (GH) treatment on bone mineral density and body composition in adults with childhood onset growth hormone deficiency. J-Endocrinol-Invest. 1996; 19(8): 524–529.PubMedGoogle Scholar
  37. 37.
    Thoren-M; Hilding-A; Baxter-RC; Degerblad-M; Wivall-Helleryd-IL; Hall-K. Serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 and-3, and the acid-labile subunit as serum markers of body composition during growth hormone (GH) therapy in adults with GH deficiency. J-Clin-Endocrinol-Metab. 1997; 82(1): 223–228.PubMedCrossRefGoogle Scholar
  38. 38.
    Toogood-AA; O’Neill-PA; Shalet-SM. Beyond the somatopause: growth hormone deficiency in adults over the age of 60 years. J-Clin-Endocrinol-Metab. 1996; 81(2): 460–465.PubMedCrossRefGoogle Scholar
  39. 39.
    Toogood-AA, Wieringa-GE, Adams-JE and Shalet-SM. Growth hormone replacement therapy in the elderly with organic growth hormone deficiency: Do they benefit? Abstract in 79th annual meeting of the Endocrine societyjunell-14, 1997.Google Scholar
  40. 40.
    Wollmann-HA; Schonau-E; Blum-WF; Meyer-F; Kruse-K; Ranke-MB. Dosedependent responses in insulin-like growth factors, insulin-like growth factorbinding protein-3 and parameters of bone metabolism to growth hormone therapy in young adults with growth hormone deficiency. Horm-Res. 1995; 43(6): 249–256.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • S J Howell
    • 1
  • A Rahim
    • 1
  • S M Shalet
    • 1
  1. 1.Department of EndocrinologyChristie Hospital NHS TrustWithingtonUK

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