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The Cardiovascular Risk of GH-Deficient Adolescents

Departments of Molecular and Clinical Endocrinology and Oncology (A.C., C.D.S., F.O., G.L.), Pediatrics (M.S.), and Internal Medicine I (L.S.), University Federico II of Naples, 80131 Naples, Italy

Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Ph.D., Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Via S. Pansini 5, 80131 Naples, Italy. E-mail: . colao{at}unina.it

Abstract

To investigate the onset of the cardiovascular impairment in patients with GH deficiency (GHD), we prospectively studied cardiovascular risk parameters, cardiac mass and performance (by echocardiography) in 10 adolescent patients (5 with isolated GHD and 5 with multiple GHD) who reached their final height before GH replacement withdrawal, 6 months after GH replacement withdrawal, and 6 months after GH treatment was restarted, and in 10 sex- and age-matched controls.

At study entry, when compared with controls, GHD adolescents had lower IGF-I levels (although still in the normal age range) and high-density lipoprotein (HDL)-cholesterol levels, higher total/HDL-cholesterol ratio, lower triglyceride levels, higher fibrinogen levels, and lower heart rate, systolic blood pressure, and early-to-late mitral flow velocity ratio (E/A). Left ventricular (LV) mass index and ejection fraction were normal. Six months after GH withdrawal, IGF-I levels decreased remarkably in all cases (from 176.6 ± 8.3 to 77.5 ± 8.9 µg/liter; P < 0.001), whereas low-density lipoprotein-cholesterol and triglyceride levels significantly increased. The total/HDL-cholesterol ratio (from 3.89 ± 0.1 to 4.74 ± 0.2; P < 0.05) and fibrinogen levels (from 261 ± 7.1 to 287.5 ± 6.4 mg/dl; P < 0.05) also significantly increased compared with study entry, without any change in the other parameters. In contrast, both LV mass index (from 94.2 ± 1.6 to 87.8 ± 1.7 g/m²; P = 0.05) and E/A (from 1.32 ± 0.05 to 1.12 ± 0.03; P < 0.01) decreased, although remaining in the normal range. Six months after restarting GH replacement (at a median dose of 10 µg/kg·d), lipid and cardiac parameters were brought back to the levels measured at study entry, but in no patient did IGF-I levels reach the 50th centile for age. HDL-cholesterol levels (P < 0.0001), heart rate (P < 0.05), systolic blood pressure (P < 0.01), LV ejection fraction (P < 0.005), and E/A (P < 0.0001) remained lower, whereas total/HDL-cholesterol ratio (P < 0.01), triglycerides, and fibrinogen levels (P < 0.05) remained higher than controls.

In conclusion, GH discontinuation is inappropriate in adolescents with severe GHD, inducing impairment of lipid profile and cardiac morphology and performance. Because the results on the cardiovascular system and on the lipid profile were suboptimal, it is likely that the GH dose in severe GHD adolescents should be higher.

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