Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults.

Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid artery intima-media thickness (IMT) and reduced distensibility] are more prevalent. As GH replacement can reverse some risk factors of atherosclerosis, the present study examined the effect of GH treatment on morphological and functional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18 months. IMT of the common carotid artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial artery were measured by B mode ultrasound before and at 3, 6, 12, and 18 months of treatment, and values were compared with those in 12 age-matched control men. Serum concentrations of lipids, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were also measured. In GHD men before treatment the IMTs of the CCA [mean(SD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater (P < 0.001) than those in control men [0.52(0.07) and 0.65(0.07) mm, respectively]. GH treatment normalized the IMT of the CCA by 6 months [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r = -0.53; P < 0.0001). There was a significant improvement in flow-mediated EDD of the brachial artery at 3 months, which was sustained at 6 and 18 months of GH treatment (P < 0.05). GH treatment increased high density lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low density lipoprotein cholesterol and was without effect on lipoprotein(a). There was no correlation between plasma lipids and changes in IMT or EDD of the arteries examined. In conclusion, GH treatment of hypopituitary GHD men reverses early morphological and functional atherosclerotic changes in major arteries and, if maintained, may reduce vascular morbidity and mortality. GH seems to act via IGF-I, which is known to have important effects on endothelial cell function.

[1]  M. Scanlon,et al.  Endothelial dysfunction in growth hormone-deficient adults , 1998 .

[2]  P. Carroll,et al.  Growth Hormone Deficiency in Adulthood and the Effects of Growth Hormone Replacement: A Review , 1998 .

[3]  P. Tsao,et al.  Adhesiveness of mononuclear cells in hypercholesterolemic humans is normalized by dietary L-arginine. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[4]  L. Ho,et al.  Growth hormone (GH) replacement reduces total body fat and normalizes insulin sensitivity in GH-deficient adults: a report of one-year clinical experience. , 1997 .

[5]  R. D'Agostino,et al.  Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis. , 1997, The New England journal of medicine.

[6]  B. Biondi,et al.  Increased arterial intima-media thickness in childhood-onset growth hormone deficiency. , 1997, The Journal of clinical endocrinology and metabolism.

[7]  P. Tsao,et al.  Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. , 1997, Journal of the American College of Cardiology.

[8]  K. Parker,et al.  Abnormal carotid arterial wall dynamics in symptom-free hypopituitary adults. , 1997, European journal of endocrinology.

[9]  L. Hagmar,et al.  Increased cerebrovascular mortality in patients with hypopituitarism , 1997, Clinical endocrinology.

[10]  G. Brabant,et al.  Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. , 1996, The Journal of clinical investigation.

[11]  R. Clayton,et al.  The effect of hypopituitarism on life expectancy. , 1996, The Journal of clinical endocrinology and metabolism.

[12]  M. Radomski,et al.  Nitric oxide--biological mediator, modulator and factor of injury: its role in the pathogenesis of atherosclerosis. , 1995, Atherosclerosis.

[13]  M. Gammage,et al.  Cardiovascular function and glucocorticoid replacement in patients with hypopituitarism , 1995, Clinical endocrinology.

[14]  B. Bengtsson,et al.  Growth hormone-deficient adults are insulin-resistant. , 1995, Metabolism: clinical and experimental.

[15]  P. Tsao,et al.  Discordant Effects of Dietary L-Arginine on Vascular Structure and Reactivity in Hypercholesterolemic Rabbits , 1995, Journal of cardiovascular pharmacology.

[16]  D. Johnston,et al.  The effects of short and long-term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance. , 1995, The Journal of clinical endocrinology and metabolism.

[17]  H. de Boer,et al.  Clinical aspects of growth hormone deficiency in adults. , 1995, Endocrine reviews.

[18]  D. Grobbee,et al.  Carotid artery intima‐media thickness as an indicator of generalized atherosclerosis , 1994, Journal of internal medicine.

[19]  G. Watts,et al.  The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients , 1994, Clinical endocrinology.

[20]  W. Hsueh,et al.  Endothelial-Dependent Vascular Effects of Insulin and Insulin-Like Growth Factor I in the Perfused Rat Mesenteric Artery and Aortic Ring , 1994, Diabetes.

[21]  A. Nicolaides,et al.  Carotid intima‐media thickness: correlation with the British Regional Heart Study risk score , 1994, Journal of internal medicine.

[22]  B. Tönshoff,et al.  Direct demonstration of insulin-like growth factor-I-induced nitric oxide production by endothelial cells. , 1994, Kidney international.

[23]  G. Gamble,et al.  Estimation of Arterial Stiffness, Compliance, and Distensibility From M‐Mode Ultrasound Measurements of the Common Carotid Artery , 1994, Stroke.

[24]  D. Celermajer,et al.  Cigarette Smoking Is Associated With Dose‐Related and Potentially Reversible Impairment of Endothelium‐Dependent Dilation in Healthy Young Adults , 1993, Circulation.

[25]  L. Wilhelmsen,et al.  Cardiovascular risk factors in adult patients with growth hormone deficiency. , 1993, Acta endocrinologica.

[26]  J. Salonen,et al.  Ultrasound B-mode imaging in observational studies of atherosclerotic progression. , 1993, Circulation.

[27]  A. Nicolaides,et al.  Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults , 1992, The Lancet.

[28]  P. Tsao,et al.  Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. , 1992, The Journal of clinical investigation.

[29]  B. Bengtsson,et al.  Premature mortality due to cardiovascular disease in hypopituitarism , 1990, The Lancet.

[30]  M. Boes,et al.  Insulin, insulin-like growth factors, and vascular endothelium. , 1988, The American journal of medicine.

[31]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[32]  V. McKusick,et al.  Isolated human growth hormone deficiency. III. Insulin secretion in sexual ateliotic dwarfism , 1968 .

[33]  A. Stan,et al.  Dietary L-arginine decreases myointimal cell proliferation and vascular monocyte accumulation in cholesterol-fed rabbits. , 1998, Atherosclerosis.

[34]  P. Tsao,et al.  Regression or progression. Dependency on vascular nitric oxide. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[35]  J. Devlin,et al.  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. , 1996, European journal of endocrinology.

[36]  T. Ziegler.  Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. , 1994, JPEN. Journal of parenteral and enteral nutrition.