Table of Contents 21-4

Cardiovascular Effects of Adolescent Growth Hormone Deficiency

The metabolic effects of growth hormone (GH) led to FDA-approval of rhGH therapy for GH deficiency (GHD) in adults, even though they have no prospect of height benefits. These effects include improvements in body composition, serum lipid levels, and cardiac function, among others. Lanes and colleagues sought to determine whether cardiovascular function is already altered in adolescents with GHD. These authors compared 10 adolescents with GHD on GH treatment (0.03 mg/kg/d for a mean of 3.8 ± 1.1 yr), 12 adolescents with untreated GHD (4 of whom had previously received 1.6 ± 0.2 yr of treatment but had been off GH treatment for 3.4 ± 1.2 yr due to financial reasons) and 14 healthy adolescent controls. The 3 groups were similar in chronologic age, bone age, height (but not height z-score), BMI, pubertal distribution (65-70% Tanner stages 2-4; remainder prepubertal), blood pressure, and pulse. GHD was defined by abnormally low serum IGF-I and IGFBP-3 concentrations plus failure on clonidine/L-DOPA stimulation testing (peak GH concentrations were 3.2 ± 2.4 and 3.0 ± 2.3 µg/L with a range of 0.9–5.6 µg/L).

A pediatric cardiologist and his technician, blinded to the GH status of the adolescents, performed echocardiography, carotid sonography, and measurement of endothelium-dependent vasodilation. For this last measurement, Doppler ultrasonography was used to quantify right brachial artery blood flow and brachial artery diameter before and 45 to 60 seconds after release of 5 minutes of 300 mm Hg applied by a standard sphygmomanometer cuff to the forearm (to induce hyperemia). They also measured, during echocardiography, the epicardial adipose tissue on the right ventricle, which was described in 2003 as a correlate with MRI measurement of abdominal visceral fat, clinical parameters of metabolic syndrome, and hence, cardiovascular risk in adults.¹

Left ventricular mass was significantly lower in the untreated and treated GHD groups than the normal controls, although left ventricular posterior wall and interventricular septal thicknesses were both similar across groups. Left ventricular ejection fraction (%) was also similar, but the controls had significantly larger end systolic and end diastolic volumes than the 2 GHD groups. Carotid artery intima-media thickness did not differ, but the hyperemia-induced increases in brachial artery diameter and blood flow were both related to GH status; vasodilation was lower in the untreated GHD group than in the treated and control groups, and blood flow was greatest in the treated GHD group. Epicardial adipose tissue, which correlated positively with BMI in all 3 groups, was significantly greater in the untreated GHD adolescents than the other groups. Thus, GHD has been associated with decreased cardiac size, increased large-artery stiffness (IGF-I has a direct releasing effect on nitric oxide, an endothelial relaxing factor), and increased epicardial adipose tissue (a correlate of cardiovascular risk factors in adults).

Lanes R, Soros A, Flores K, Gunczler P, Carrillo E, Bandel J. Endothelial function, carotid artery intima-media thickness, epicardial adipose tissue, and left ventricular mass and function in growth hormone-deficient adolescents: Apparent effects of growth hormone treatment on these parameters. J Clin Endocrinol Metab. 2005;90:3978–3982.

Editor’s Comment: Quite extensive data have been accumulating on the cardiovascular effects of GH and GHD. I refer the reader to references 2 and 3 for reviews of GH effects and reference 4 for review of IGF-I effects on cardiovascular system. Growth hormone replacement therapy for GHD in adults is too new to allow analysis of the ultimate question; that is, if rhGH can significantly ameliorate the increased cardiovascular mortality seen in adults with GHD. The interim markers are encouraging; however, most of the work has examined adults.⁵ Lanes and colleagues alert us that potentially detrimental cardiovascular changes can be seen in patients with GHD as early as adolescence. Thus, cardiovascular health joins body composition issues (muscle mass and bone mineralization) as factors to consider in optimizing GH treatment during the transition period, the time between cessation of linear growth and attainment of full adult body maturity.⁶

Adda Grimberg, MD

References - (linked to )

1. Iacobellis G, Ribaudo MC, Assaef F, et al. J Clin Endocrinol Metab. 2003;88:5163–5168.
2. Gola M, Bonadonna S, Doga M, Giustina. J Clin Endocrinol Metab. 2005;90:1864–1870.
3. Colao A. Horm Res. 2004;62(Suppl 3):42–50.
4. Kaplan RC, Strickler HD, Rohan TE, Muzumdar R, Brown DL. Cardiol Rev. 2005;13:35–39.
5. Colao A, Di Somma C, Vitale G, Filippella M, Lombardi G. Treat Endocrinol. 2003;2:347–356.
6. Shalet S. Horm Res. 2004;62(Suppl 4):15–22.