SYNDROME OF GROWTH HORMONE DEFICIENCY IN ADULTS – EFFECTS OF GROWTH HORMONE REPLACEMENT THERAPY
Keywords:
growth hormone deficiency, body composition, bone mineral density, atherogenesis, quality of life
Abstract
Background. After the cessation of longitudinal growth, growth hormone (GH) continues to subserve an important role in the regulation of body metabolism (stimulation of lipolysis and lipid oxidation, protein synthesis, insulin antagonism, and sodium and water retention) to optimise body composition and function. Most patients with hypopituitarism exhibit the syndrome of GH deficiency with a number of abnormal features which can be reversed with recombinant GH replacement therapy.
Conclusions. GH-deficient patients have decreased lean body mass and bone mineral content, increased fat mass, reduced muscle strength and exercise performance, dyslipidemia and increased prevalence of other risk factors for atherosclerosis. They exhibit increased cardiovascular morbidity and mortality and impaired quality of life. It has been shown that GH replacement normalises body composition and exercise capacity, reverses early atherosclerotic changes in major arteries, improves cognitive functions and quality of life. As the treatment with recombinant GH is life-long and expensive it should be offered to patients who exhibit most symptoms and have been proven to have severe GH-deficiency.
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References
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Salomon F, Cuneo RC, Hesp R, Sönksen 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: 1797–803.
De Boer H, Blok GJ, Van der Veen E. Clinical aspects of growth hormone deficiency in adults. Endocr Rev 1995; 16: 63–86.
RosØn T, Wiren L, Wilhelmsen L, Wiklund I, Bengtsson BA. Decreased psychological well-being in adult patients with growth hormone deficiency. Clin Endocrinol 1994; 40: 111–6.
Vance ML, Mauras N. Growth hormone therapy in adults and children. N Engl J Med 1999; 341: 1206–16.
Carrol PV, Christ ER, Bengtsson BA et al. Growth hormone deficiency in adulthood and the effect of growth hormone replacement: a review. Growth hormone research society scientific committee. J Clin Endocrinol Metab 1998; 83: 382–95.
Cuneo RC, Salomon F, Sönksen PH. The syndrome of growth hormone deficiency in adults. In: Juul A, Jørgensen JOL eds. Growth hormone in adults: physiological and clinical aspects. Cambridge University Press, 1996: 145–67.
Markussis V, Beshyah SA, Fisher C, Sharp P, Nicolaides AN, Johnston DG. Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet 1992; 340: 1188–92.
Bates AS, Van’t Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996; 81: 1169–72.
Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth hormone research society Workshop on adult growth hormone deficiency. J Clin Endocrinol Metab 1998; 83: 379–81.
RosØn T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990; 336: 285–8.
Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol 1997; 46: 75–81.
Cuneo RC, Salomon F, Watts GF, Hesp R, Sönksen PH. Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism 1993; 42: 1519–23.
RosØn T, Eden S, Larson G, Wilhelmsen L, Bengtsson BA. Cardiovascular risk factors in adult patients with growth hormone deficiency. Acta Endocrinol (Copenh) 1993; 129: 195–200.
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Al-Shoumer KAS, Gray R, Anyaoku V et al. Effects of four years’ treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH-deficient adults. Clin Endocrinol 1998; 48: 795–802.
Pfeifer M, Verhovec R, Žižek B, Preželj J, Poredoš P, Clayton RN. Growth hormone (GH) treatment reverses early atherosclerotic changes in GHdeficient adults. J Clin Endocrinol Metab 1999; 84: 453–7.
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De Boer H, Blok GJ, Van der Veen E. Clinical aspects of growth hormone deficiency in adults. Endocr Rev 1995; 16: 63–86.
RosØn T, Wiren L, Wilhelmsen L, Wiklund I, Bengtsson BA. Decreased psychological well-being in adult patients with growth hormone deficiency. Clin Endocrinol 1994; 40: 111–6.
Vance ML, Mauras N. Growth hormone therapy in adults and children. N Engl J Med 1999; 341: 1206–16.
Carrol PV, Christ ER, Bengtsson BA et al. Growth hormone deficiency in adulthood and the effect of growth hormone replacement: a review. Growth hormone research society scientific committee. J Clin Endocrinol Metab 1998; 83: 382–95.
Cuneo RC, Salomon F, Sönksen PH. The syndrome of growth hormone deficiency in adults. In: Juul A, Jørgensen JOL eds. Growth hormone in adults: physiological and clinical aspects. Cambridge University Press, 1996: 145–67.
Markussis V, Beshyah SA, Fisher C, Sharp P, Nicolaides AN, Johnston DG. Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet 1992; 340: 1188–92.
Bates AS, Van’t Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996; 81: 1169–72.
Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth hormone research society Workshop on adult growth hormone deficiency. J Clin Endocrinol Metab 1998; 83: 379–81.
RosØn T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990; 336: 285–8.
Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol 1997; 46: 75–81.
Cuneo RC, Salomon F, Watts GF, Hesp R, Sönksen PH. Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism 1993; 42: 1519–23.
RosØn T, Eden S, Larson G, Wilhelmsen L, Bengtsson BA. Cardiovascular risk factors in adult patients with growth hormone deficiency. Acta Endocrinol (Copenh) 1993; 129: 195–200.
Beshyah SA, Henderson A, Niththyananthan R et al. The effect of short and long term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance. J Clin Endocrinol Metab 1995; 80: 356–63.
Al-Shoumer KAS, Gray R, Anyaoku V et al. Effects of four years’ treatment with biosynthetic human growth hormone (GH) on glucose homeostasis, insulin secretion and lipid metabolism in GH-deficient adults. Clin Endocrinol 1998; 48: 795–802.
Pfeifer M, Verhovec R, Žižek B, Preželj J, Poredoš P, Clayton RN. Growth hormone (GH) treatment reverses early atherosclerotic changes in GHdeficient adults. J Clin Endocrinol Metab 1999; 84: 453–7.
Johansson JO, Landin K, Tengborn L, RosØn T, Bengtsson BA. High fibrinogen and plasminogen activator inhibitor activity in growth hormone deficient adults. Arterioscler Thromb 1994; 14: 434–7.
Capaldo B, Patti L, Oliviero U et al. Increased arterial intima-media thickness in childhood onset growth hormone deficiency. J Clin Endocrinol Metab 1997; 82: 1378–81.
Jørgensen JOL, Thuesen L, Müller J, Ovesen P, Skakkebæk NE, Christiansen JS. Three years of growth hormone treatment in growth hormone deficient adults: near normalisation of body composition and physical performance. Eur J Endocrinol 1994; 130: 224–8.
Hwu CM, Kwok CF, Lai TY et al. Growth hormone (GH) replacement reduces body fat and normalises insulin sensitivity in GH deficient adults: a report of one year clinical experience. J Clin Endocrinol Metab 1997; 82: 3285–92.
Amato G, Carella C, Fazio S et al. Body composition, bone metabolism, and heart structure and function in growth hormone deficient adults before and after GH replacement therapy at low doses. J Clin Endocrinol Metab 1993; 77: 1671–6.
Merola B, Cittadini A, Colao A et al. Cardiac structural and functional abnormalities in adult patients with growth hormone deficiency. J Clin Endocrinol Metab 1993; 77: 1658–61.
Caidahl K, Eden S, Bengtsson BA. Cardiovascular, and renal effects of growth hormone. Clin Endocrinol 1994; 40: 393–400.
Thuesen L, Jørgensen JOL, Muller JR et al. Short and long-term cardiovascular effect of growth hormone therapy in growth hormone deficient adults. Clin Endocrinol 1994; 41: 615–20.
Johannsson G, Bengtsson BA, Andersson B, Isgaard J, Caidahl K. Long term cardiovascular effects of growth hormone treatment in GH-deficient adults. Preliminary data in a small group of patients. Clin Endocrinol 1996; 45: 305–14.
Cuocolo A, Nicolai E, Colao A et al. Improved left ventricular function after growth hormone replacement in patients with hypopituitarism: assessment with radionuclide angiography. Eur J Nucl Med 1996; 23: 390–4.
RosØn T, Hansson T, Granhed H, Szucs J, Bengtsson BA. Reduced bone mineral content in adult patients with growth hormone deficiency. Eur J Endocrinol 1995; 132: 727–9.
RosØn T, Wilhelmsen L, Landin-Wilhelmsen K, Lappas G, Bengtsson BA. Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur J Endocrinol 1997; 137: 240–5.
Vandeweghe M, Taelman P, Kaufman JM. Short and long term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone deficient males. Clin Endocrinol 1993; 39: 409–15.
Baum HBA, Biller BMK, Finkelstein JS et al. Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency: A randomised, placebo-controlled trial. Ann Intern Med 1996; 125: 883–90.
Johannsson AG, Burman P, Westermark K, Ljunghall S. The bone mineral density in acquired growth hormone deficiency correlates with circulating insulin-like growth factor. J Intern Med 1992; 232: 447–52.
Colao A, Di Somma C, Pivonello R et al. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 1999; 84: 1919–24.
Biller BMK, Sesmilo G, Baum HBA et al. Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men with adult-onset GH deficiency. J Clin Endocrinol Metab 2000; 85: 970–6.
Stabler B, Turner JR, Girdler SS, Light KC, Underwood LE. Reactivity to stress and psychological adjustment in adults with pituitary insufficiency. Clin Endocrinol 1992; 6: 467–73.
Sanmarti A, Lucas A, Hawkins F et al. Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Eur J Endocrinol 1999; 141: 481–9.
McKenna SP, Doward LC. Quality of life assessment of adults with growth hormone deficiency. Implications for drug therapy. Pharmaco Econ 1994; 6: 434–41.
Burman P, Broman JE, Hetta J et al. 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: 3585–90.
Holmes SJ, Shalet SM. Characteristics of adults who wish to enter a trial of growth hormone replacement. Clin Endocrinol 1995; 42: 613–8.
Holmes SJ, Shalet SM. Factors influencing the desire for long term growth hormone replacement in adults. Clin Endocrinol 1995; 43: 151–7.
Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 1998; 19: 717–97.
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: 1081–8.
Zadik Z, Chalew SA, McCarter Jr. RJ, Meistas M, Kowarski AA. The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 1985; 60: 513–6.
Ho KY, Evans WS, Blizzard RM et al. Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab 1987; 64: 51–8.
Press M. Growth hormone and metabolism. Diabetes Metab Rev 1988; 4: 391–414.
Davidson MB. Effect of growth hormone on carbohydrate and lipid metabolism. Endocr Rev 1987; 8: 115–31.
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: 427–31.
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: 1371–7.
Hilding A, Hall K, Wivall-Helleryd IL et al. Serum levels of insulin-like growth factor I in 152 patients with growth hormone deficiency, aged 19–82 years, in relation to those in healthy subjects. J Clin Endocrinol Metab 1999; 84: 2013–3.
Johannsson G, RosØn T, Bengtsson BA. Individualised dose titration of growth hormone (GH) during GH replacement in hypopituitary adults. Clin Endocrinol 1997; 47: 571–81.
Drake WM, Coyte D, Camacho-Hubner C et al. Optimising growth hormone replacement therapy by dose titration in hypopituitary adults. J Clin Endocrinol Metab 1998; 83: 3913–9.
Murray RD, Skillicorn CJ, Howell SJ, Lissett CA, Rahim A, Shalet SM. Dose titration and patient selection increases the efficacy of GH replacement in severely GHD adults. Clin Endocrinol 1999; 50: 749–57.
Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH. Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. J Appl Physiol 1991; 70: 688–94.
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Published
2017-04-15
How to Cite
1.
Pfeifer marija. SYNDROME OF GROWTH HORMONE DEFICIENCY IN ADULTS – EFFECTS OF GROWTH HORMONE REPLACEMENT THERAPY. TEST ZdravVestn [Internet]. 15Apr.2017 [cited 5Aug.2024];70(5). Available from: http://vestnik-dev.szd.si/index.php/ZdravVest/article/view/2564
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