Horm Metab Res 2006; 38(1): 16-21
DOI: 10.1055/s-2006-924970
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Short-term Therapy with Recombinant Human Growth Hormone (GH) on Metabolic Parameters and Preclinical Atherosclerotic Markers in Hypopituitary Patients with Growth Hormone Deficiency

S.  Benedini1 , L.  Dalle Carbonare2 , N.  Albiger1 , M.  Scanarini4 , F.  Bilora3 , F.  Petrobelli3 , S.  Giannini2 , F.  Mantero1 , C.  Scaroni1
  • 1Endocrine Unit, Dept. of Medical and Surgical Sciences, University of Padua, Italy
  • 2Clinica Medica I, Dept. of Medical and Surgical Sciences, University of Padua, Italy
  • 32nd Internal Medicine Unit, Dept. of Medical and Surgical Sciences, University of Padua, Italy
  • 4Neurosurgery, Hospital of Padua, Italy
Weitere Informationen

Publikationsverlauf

Received 30 March 2005

Accepted after revision 9 August 2005

Publikationsdatum:
13. Februar 2006 (online)

Abstract

Objective: This study examines the effects of growth hormone replacement on body composition, insulin sensitivity, lipid profile, endothelial dysfunction and carotid intima media thickness in patients with adult-onset growth-hormone (GH) deficiency. Methods: Twelve patients with severe GH deficiency received GH replacement for one year. In all patients, the following parameters were evaluated before and after six and twelve months of therapy: fasting glucose, insulin levels and lipid profile, bone mineral density and body composition. Carotid intima media thickness and brachial flow-mediated dilatation were also evaluated by arterial ultrasonography at basal condition and after one year of therapy. Results: No significant changes were seen in body weight and blood pressure, total fat and lean mass, or bone mineral density after six months of GH replacement. There was an increase in triglycerides (p = 0.05), while total and HDL cholesterol, blood glucose, insulin levels did not change significantly. After twelve months, an increase in lean mass and a decrease in fat mass (p < 0.01 vs. baseline), a decrease in insulin resistance (p < 0.01 vs. six months; p = 0.01 vs. baseline) and a decrease in triglycerides (p < 0.01) were observed. Intima media thickness was greater in GH deficiency than in controls (p = 0.01) before therapy, and was unchanged after twelve months of therapy, whereas the flow-mediated dilatation tended to improve (p = 0.05). Conclusions: GH replacement is able to reverse typical metabolic and body composition alterations in patients with adult GH deficiency after twelve months, but it is unable to revert the vascular alteration completely. Flow-mediated dilatation seems to be a more precocious marker of the remission of arterial damage.

References

  • 1 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;  98 379-381
  • 2 Carroll P V, Christ E R, Bengtsson B-Å, Carlsson L, Christiansen J S. et al . Growth hormone deficiency in adulthood and the effects of growth hormone replacement: A Review.  J Clin Endocrinol Metab. 1998;  83 382-395
  • 3 Holmes S J, Economou G, Whitehouse R W, Adams J E, Shalet S M. Reduced bone mineral density in patients with adult onset growth hormone deficiency.  J Clin Endocrinol Metab. 1994;  78 669-674
  • 4 Shahi M, Beshyah S A, Hackett D, Sharp P S, Johnston D G, Foale R A. Myocardial dysfunction in treated adult hypopituitarism: a possible explanation for increased cardiovascular mortality.  Br Heart J. 1992;  67 92-96
  • 5 Rosen T, Bengtsson B-Å. Premature mortality due to cardiovascular disease in hypopituitarism.  Lancet. 1990;  336 285-288
  • 6 Beshyah S A, Johnston D G. Cardiovascular disease and risk factors in adults with hypopituitarism.  Clin Endocrinol. 1999;  50 1-15
  • 7 Johansson J O, Fowelin J, Landin K, Lager I, Bengtsson B A. Growth hormone-deficient adults are insulin resistant.  Metab Clin Exp. 1995;  44 1126-1129
  • 8 Hew F L, Koschmann M, Christopher M. et al . Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity.  J Clin Endocrinol Metab. 1996;  81 555-564
  • 9 De Boer H, Blok G J, Voerman H J, Phillips M, Schouten J A. Serum lipid levels in growth hormone-deficient men.  Metab Clin Exp. 1994;  43 199-203
  • 10 Monson J P. Long-term experience with GH replacement therapy: efficacy and safety.  Eur J Endocrinol. 2003;  148 Suppl 2 S9-S14
  • 11 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . .  Diabetes Care. 1998;  21 (Suppl 1) S5-S19
  • 12 Ravikumar R, Deepa R, Shanthirani C, Mohan V. Comparison of carotid intima-media thickness, arterial stiffness, and brachial artery flow mediated dilatation in diabetic and nondiabetic subjects (The Chennai Urban Population Study [CUPS-9]).  Am J Cardiol. 2002;  90 702-107
  • 13 Giannini S, D’Angelo A, Carraro G, Nobile M, Rigotti P, Bonfante L, Marchini F, Zaninotto M, Dalle Carbonare L, Sartori L, Crepaldi G. Alendronate prevents further bone loss in renal transplant recipients.  J Bone Miner Res. 2001;  16 (11) 2111-2117
  • 14 Perseghin G, Mazzaferro V, Benedini S, Pulvirenti A, Coppa J, Regalia E, Luzi L. Resting energy expenditure in diabetic and non-diabetic patients with liver cirrhosis: relationship with insulin sensitivity, and effect of liver transplantation and of immunosuppressive therapy.  Am J Clin Nutr. 2002;  76 541-548
  • 15 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
  • 16 McCallum R W, Petrie J R, Dominiczak A F, Connell M C. Growth Hormone deficiency and vascular risk.  Clin Endocrinol. 2002;  57 11-24
  • 17 Twickler T B, Cramer M JM, Dallinga-Thie G M, Chapman M J, Erkelens D W, Koppeschaar H PF. Adult-Onset Growth Ormone Deficiency: Relation of Postprandial Dyslipidemia to Premature Atherosclerosis.  J Clin Endocrinol Metab. 2003;  88 (6) 2479-2488
  • 18 Bengtsson B-Å, Roger A BS, Bennmarker H, Monson J P. et al . Growth hormone replacement therapy is not associated with any increase in mortality. KIMS Study Group.  J Clin Endocrinol Metab. 1999;  84 3929-3935
  • 19 Abdu T A, Elhadd T A, Buch H, Barton D, Neary R, Clayton R N. Recombinant GH replacement in hypopituitary adults improves endothelial cell function and reduces calculated absolute and relative coronary risk.  Clin Endocrinol. 2004;  61 387-393
  • 20 Colao A, Di Somma C, Rota F, Pivonello R, Cristina Savanelli M, Spiezia S, Lombardi G. Short-term effects of Growth Hormone (GH) treatment or deprivation on cardiovascular risk parameters and intima-media thickness at carotid arteries in patients with severe GH deficiency.  J Clin Endocrinol Metab. 2005;  25 [Epub ahead of print]
  • 21 Misra A, Vikram N K. Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots.  Nutrition. 2003;  19 457-466
  • 22 Lattuada G, Costantino F, Caumo A, Scifo P, Ragogna F, De Cobelli F, Del Maschio A, Luzi L, Perseghin G. Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients.  Diabetologia. 2005;  48 741-747

Stefano Benedini, M. D.

U.O. Endocrinology · Istituto di Semeiotica Medica

Via Ospedale 105 · 35128 Padua · Italy

Telefon: +39 (049) 821 30 00

Fax: +39 (049) 65 73 91

eMail: stefanobenedini@hotmail.com