Effect of 5 Years of GH Replacement on Atherosclerosis

NCT00462475 | Completed

• 1 other identifier: NeuroendoUnit-3
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Adult patients with hypopituitarism under adequate conventional hormone replacement therapy have reduced life expectancy due to excess vascular events (1-4). Deficiency in GH secretion (GHD) is likely to play a major role in determining the excess mortality, since it is associated with lipid abnormalities, visceral adiposity, glucose intolerance, insulin resistance, hypertension, cardiac abnormalities and increased intima-media thickness (IMT) at major arteries (5). Beneficial effects of growth hormone (GH) replacement on cardiovascular risk factors have been demonstrated in several studies of hypopituitary GHD patients (5). GH replacement improves body composition and lipid profile (5): it is accepted that management of dyslipidaemia is crucial in primary and secondary prevention of cardiovascular disease and part of the excess vascular risk associated with hypopituitarism is likely to be due to dyslipidaemia (6). A meta-analysis of blinded, randomized, placebo-controlled trials with low doses and long-duration GH treatment showed that GH replacement has beneficial effects on cardiovascular risk by improving lean and fat body mass, total and LDL cholesterol levels, and diastolic blood pressure (7). Besides, GH replacement also induces improvement in cardiovascular markers (8), and cardiac performance (9). In small cohorts of GHD adults, beneficial effects of GH replacement for 6-24 mos have also been reported on surrogate parameters of atherosclerosis, such as intima-media thickness (IMT) at major arteries (10-13), while 6 months of GH deprivation is associated with an impairment of the cardiovascular risk profile (12). In a consistent series of men and women with hypopituitarism we reported, however, that two years of GH replacement is not adequate to normalize IMT levels at common carotid arteries (13). To give further insights on the likelihood of reversal of early atherosclerosis in severe GHD patients after prolonged GH replacement, we designed this 5-yr prospective, controlled study. Only men aged ≤50 yrs and with severe GHD were enrolled to avoid gender and aging interference (13). Main outcome measure was IMT at common carotid arteries; secondary measure was prevalence of insulin-resistance syndrome according with the American College of Endocrinology (14).

Conditions

Hypopituitarism; Pituitary Tumors; Growth Hormone Deficiency

Keywords

GH; IGF-I; GH deficiency; Atherosclerosis; Insulin resistance syndrome

Outcome Measures

Primary Outcomes (1)

• Intima-media thickness at common carotid arteries at baseline and after 5 years

  5 yrs

Secondary Outcomes (1)

• Prevalence of insulin resistance (IR) syndrome (IRS) and LDL/HDL-cholesterol ratio at baseline and after 5 years

  5 yrs

Interventions

Recombinant Growth Hormone, Genotropin (Pfizer) DRUG

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Three groups are studied: 1) Males with severe GHD undergoing GH replacement; 2) Males with severe GHD who did not undergo GH replacement because of either refusal or presence of risk factors for this treatment; 2) control men, age-matched with the patients.

You may qualify if:

• male gender
• age \<50 yrs to limit the effect of aging;
• body mass index \<30 Kg/m2;
• no familial or personal history of cardiovascular diseases;
• no concomitant treatment with drugs known to interfere with glucose or lipid metabolism or to influence blood pressure at the time of study entry;
• no previous GH treatment

You may not qualify if:

• female gender
• age \>50 yrs;
• body mass index ≥30;
• familial or personal history of cardiovascular diseases;
• previous and present treatments with drugs known to interfere with glucose or lipid metabolism or to influence blood pressure;
• previous GH treatment in adult age
• GHD of childhood onset
• GHD due to previous Cushing's disease

Sponsors & Collaborators

• Federico II University: lead

Study Sites (1)

Department of Molecular and Clinical Endocirnology and Oncology University Federico II of Naples

Naples, 80131, Italy

Location

Related Publications (22)

• Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990 Aug 4;336(8710):285-8. doi: 10.1016/0140-6736(90)91812-o.

  PMID: 1973979 RESULT

• Bulow B, Hagmar L, Mikoczy Z, Nordstrom CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol (Oxf). 1997 Jan;46(1):75-81. doi: 10.1046/j.1365-2265.1997.d01-1749.x.

  PMID: 9059561 RESULT

• Bates AS, Van't Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996 Mar;81(3):1169-72. doi: 10.1210/jcem.81.3.8772595.

  PMID: 8772595 RESULT

• Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, Sheppard MC, Stewart PM. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet. 2001 Feb 10;357(9254):425-31. doi: 10.1016/s0140-6736(00)04006-x.

  PMID: 11273062 RESULT

• Colao A, Di Somma C, Savanelli MC, De Leo M, Lombardi G. Beginning to end: cardiovascular implications of growth hormone (GH) deficiency and GH therapy. Growth Horm IGF Res. 2006 Jul;16 Suppl A:S41-8. doi: 10.1016/j.ghir.2006.03.006. Epub 2006 May 11.

  PMID: 16690338 RESULT

• Abdu TA, Neary R, Elhadd TA, Akber M, Clayton RN. Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities. Clin Endocrinol (Oxf). 2001 Aug;55(2):209-16. doi: 10.1046/j.1365-2265.2001.01320.x.

  PMID: 11531927 RESULT

• Maison P, Griffin S, Nicoue-Beglah M, Haddad N, Balkau B, Chanson P; Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials. Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials. J Clin Endocrinol Metab. 2004 May;89(5):2192-9. doi: 10.1210/jc.2003-030840.

  PMID: 15126541 RESULT

• Gola M, Bonadonna S, Doga M, Giustina A. Clinical review: Growth hormone and cardiovascular risk factors. J Clin Endocrinol Metab. 2005 Mar;90(3):1864-70. doi: 10.1210/jc.2004-0545. Epub 2004 Dec 7.

  PMID: 15585563 RESULT

• Colao A, Marzullo P, Di Somma C, Lombardi G. Growth hormone and the heart. Clin Endocrinol (Oxf). 2001 Feb;54(2):137-54. doi: 10.1046/j.1365-2265.2001.01218.x.

  PMID: 11207626 RESULT

• Pfeifer M, Verhovec R, Zizek B, Prezelj J, Poredos P, Clayton RN. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab. 1999 Feb;84(2):453-7. doi: 10.1210/jcem.84.2.5456.

  PMID: 10022400 RESULT

• Borson-Chazot F, Serusclat A, Kalfallah Y, Ducottet X, Sassolas G, Bernard S, Labrousse F, Pastene J, Sassolas A, Roux Y, Berthezene F. Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency. J Clin Endocrinol Metab. 1999 Apr;84(4):1329-33. doi: 10.1210/jcem.84.4.5595.

  PMID: 10199774 RESULT

• Colao A, Di Somma C, Rota F, Pivonello R, Savanelli MC, 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 Apr;90(4):2056-62. doi: 10.1210/jc.2004-2247. Epub 2005 Jan 25.

  PMID: 15671089 RESULT

• Colao A, Di Somma C, Cuocolo A, Spinelli L, Acampa W, Spiezia S, Rota F, Savanelli MC, Lombardi G. Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency. J Clin Endocrinol Metab. 2005 Sep;90(9):5146-55. doi: 10.1210/jc.2005-0597. Epub 2005 Jun 28.

  PMID: 15985481 RESULT

• Einhorn D, Reaven GM, Cobin RH, Ford E, Ganda OP, Handelsman Y, Hellman R, Jellinger PS, Kendall D, Krauss RM, Neufeld ND, Petak SM, Rodbard HW, Seibel JA, Smith DA, Wilson PW. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract. 2003 May-Jun;9(3):237-52. No abstract available.

  PMID: 12924350 RESULT

• Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C, Arvat E, Camanni F, Ghigo E. Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. J Clin Endocrinol Metab. 1998 May;83(5):1615-8. doi: 10.1210/jcem.83.5.4837.

  PMID: 9589665 RESULT

• Colao A, Di Somma C, Filippella M, Rota F, Pivonello R, Orio F, Vitale G, Lombardi G. Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency. Clin Endocrinol (Oxf). 2004 Sep;61(3):360-6. doi: 10.1111/j.1365-2265.2004.02105.x.

  PMID: 15355453 RESULT

• Colao A, Cerbone G, Pivonello R, Aimaretti G, Loche S, Di Somma C, Faggiano A, Corneli G, Ghigo E, Lombardi G. The growth hormone (GH) response to the arginine plus GH-releasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency. J Clin Endocrinol Metab. 1999 Apr;84(4):1277-82. doi: 10.1210/jcem.84.4.5605.

  PMID: 10199767 RESULT

• Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G, Faggiano A, Corneli G, Ghigo E, Lombardi G. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab. 1999 Jun;84(6):1919-24. doi: 10.1210/jcem.84.6.5742.

  PMID: 10372687 RESULT

• Colao A, Di Somma C, Cuocolo A, Filippella M, Rota F, Acampa W, Savastano S, Salvatore M, Lombardi G. The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study. J Clin Endocrinol Metab. 2004 Dec;89(12):5998-6004. doi: 10.1210/jc.2004-1042.

  PMID: 15579750 RESULT

• Colao A, di Somma C, Cuocolo A, Spinelli L, Tedesco N, Pivonello R, Bonaduce D, Salvatore M, Lombardi G. Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency. J Clin Endocrinol Metab. 2001 May;86(5):1874-81. doi: 10.1210/jcem.86.5.7464.

  PMID: 11344175 RESULT

• Colao A, di Somma C, Pivonello R, Cuocolo A, Spinelli L, Bonaduce D, Salvatore M, Lombardi G. The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study. J Clin Endocrinol Metab. 2002 Mar;87(3):1088-93. doi: 10.1210/jcem.87.3.8336.

  PMID: 11889170 RESULT

• Colao A, Di Somma C, Spiezia S, Savastano S, Rota F, Savanelli MC, Lombardi G. Growth hormone treatment on atherosclerosis: results of a 5-year open, prospective, controlled study in male patients with severe growth hormone deficiency. J Clin Endocrinol Metab. 2008 Sep;93(9):3416-24. doi: 10.1210/jc.2007-2810. Epub 2008 Jul 1.

  PMID: 18593773 DERIVED

MeSH Terms

Conditions

Hypopituitarism; Pituitary Neoplasms; Dwarfism, Pituitary; Atherosclerosis; Metabolic Syndrome

Interventions

Growth Hormone; Human Growth Hormone

Condition Hierarchy (Ancestors)

Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Annamaria AL Colao, Prof.

  University "Federico II"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 18, 2007
• First Posted: April 19, 2007
• Study Start: January 1, 1996
• Study Completion: December 1, 2006
• Last Updated: October 16, 2007

Record last verified: 2007-10

Locations

IT (1)