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Effect of Discontinuation of Growth Hormone Treatment on Risk Factors for Cardiovascular Disease in Adolescents Born Small for Gestational Age

Department of Pediatrics (Y.v.P., A.H.-K.), Division of Endocrinology, Sophia Children’s Hospital/Erasmus University Medical Centre, 3015 GJ Rotterdam; Institute of Epidemiology and Biostatistics (P.M.), Erasmus University Medical Centre, 3015 GJ Rotterdam; Academic Hospital of Free University (M.H.), 1081 HV Amsterdam; Wilhelmina Children’s Hospital (M.J.), 3584 EA Utrecht; Juliana Children’s Hospital (M.R.), 2566 MJ The Hague, The Netherlands

Address all correspondence and requests for reprints to: Y. K. van Pareren, M.D., Department of Pediatrics, Division of Endocrinology, Sophia Children’s Hospital, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. E-mail: vanpareren{at}zonnet.nl.

Hyperlipidemia, diabetes mellitus type 2, and coronary heart disease have been associated with being born small for gestational age (SGA). It has been reported that GH treatment induced higher insulin levels, which has led to concern regarding the long-term effect of GH treatment in predisposed individuals such as children born SGA. In this study, we assessed the effect of discontinuation of long-term GH treatment in 47 adolescents born SGA on oral glucose tolerance tests, blood pressure (BP), and serum lipid levels for two GH dosage groups (3 vs. 6 IU/m²·d). At 6 months after discontinuation of GH treatment mean (SD) age was 16.0 (2.1) yr. Mean duration of GH treatment had been 6.9 (1.5) yr. Fasting glucose levels and 120-min area under the curve for glucose 6 months after discontinuation of GH treatment showed no difference from pretreatment levels for both GH dosage groups. After discontinuation of GH treatment, fasting insulin levels returned to pretreatment levels (8.4 mU/liter), whereas the 120-min area under the curve for insulin decreased, compared with 6-yr levels (P < 0.01), regardless of GH dosage group. No significant difference was found when levels were compared with a control group. In addition, for both GH dosage groups, no significant changes in systolic and diastolic BP SD score, total cholesterol, and atherogenic index (total cholesterol/high-density lipoprotein cholesterol) were seen from 6 yr of GH until 6 months after discontinuation of GH treatment. In conclusion, in children born SGA, the GH-induced insulin insensitivity disappeared after discontinuation of GH, even after long-term GH treatment. Furthermore, the beneficial effect of GH on BP was not changed after discontinuation of GH, and most children had normal lipid levels.

This work was supported by Novo Nordisk A/S Denmark.

Abbreviations: 30-min ratio, Ratio of insulin to glucose at 30 min; 120-min ratio, ratio of insulin to glucose at 120 min; AUC, area under the curve for time concentration; BMI, body mass index; BP, blood pressure; CA, chronological age; CV, coefficient of variation; DM, diabetes mellitus; FH, full height; GHD, GH deficiency; HbA_1c, hemoglobin A_1c; HDL-c, high-density lipoprotein cholesterol; IGT, impaired glucose tolerance; LBW, low birth weight; LDL-c, low-density lipoprotein cholesterol; OGTT, oral glucose tolerance test; SGA, small for gestational age; TC, total serum cholesterol.

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