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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  )
- Iacobellis G, Ribaudo MC, Assaef F, et al. J Clin Endocrinol Metab. 2003;88:5163–5168.
- Gola M, Bonadonna S, Doga M, Giustina. J Clin Endocrinol Metab. 2005;90:1864–1870.
- Colao A. Horm Res. 2004;62(Suppl 3):42–50.
- Kaplan RC, Strickler HD, Rohan TE, Muzumdar R, Brown DL. Cardiol Rev. 2005;13:35–39.
- Colao A, Di Somma C, Vitale G, Filippella M, Lombardi G. Treat Endocrinol. 2003;2:347–356.
- Shalet S. Horm Res. 2004;62(Suppl 4):15–22.
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Current GGH - Vol. 24 No. 1
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