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PEDIATRICS Vol. 110 No. 5 November 2002, pp. 889-896

Short-Term Growth Hormone Treatment in Girls With Turner Syndrome Decreases Fat Mass and Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

Claus Højbjerg Gravholt, MD, PhD^*, Rune Weis Naeraa, MD^*,, Kim Brixen, MD, PhD^,||, Knud William Kastrup, MD^¶, Leif Mosekilde, MD, DrMedSci, Jens Otto Lunde Jørgensen, MD, DrMedSci^* and Jens Sandahl Christiansen, MD, DrMedSci^*

^* Medical Department M (Endocrinology and Diabetes) and Medical Research Laboratories, Aarhus Kommunehospital, Aarhus University Hospital, Aarhus, Denmark
Pediatric Department, Skejby Sygehus, Århus University Hospital, Aarhus, Denmark
Department of Endocrinology C, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus, Denmark
^|| Department of Endocrinology M, Odense University Hospital, Odense, Denmark
^¶ Pediatric Department, Copenhagen County Hospital, Glostrup, Denmark

--> Background. Most girls with Turner syndrome (TS) receive growth hormone (GH) treatment during childhood and adolescence, but controlled data on the effects on body composition and glucose metabolism are lacking.

Objective. To study the effects of GH treatment on insulin sensitivity, glucose metabolism, bone turnover, and body composition.

Methods. A randomized, placebo-controlled, crossover study was conducted with girls with TS. All girls with TS were treated with GH 0.1 IU/kg/d subcutaneously at bedtime or with placebo for 2 months and studied at the end of each period. Control subjects were studied once without treatment. Twelve girls with TS, aged 9.5 to 14.8 years (median: 12.9 years) and 16 age-matched control subjects (10.3–16.0 years; median: 12.1 years) were studied. Twenty-four-hour sampling of blood was performed; GH, insulin-like growth factor I (IGF-I), IGF binding proteins (IGFBPs), insulin, glucose, and lipolytic and gluconeogenic precursors were assayed, followed by an oral glucose tolerance test. Body composition was evaluated by dual-energy x-ray absorptiometry scanning and body mass index (BMI). Fasting bone markers were measured.

Results. Height was reduced in TS as compared with control subjects. In the placebo situation, 24-hour integrated GH as well as IGF-I was significantly reduced in girls with TS compared with control subjects. Controlling for differences in lean body mass (LBM; or fat mass [FM]) and sexual development did not explain the difference in 24-hour integrated GH. Differences in sexual development, BMI, FM, insulin sensitivity, and IGFBP-3 could explain the difference in IGF-I between TS and control subjects. Carbohydrate metabolism in TS was comparable with control subjects. GH treatment induced insulin resistance, with increments in fasting glucose andinsulin, as well as 24-hour insulin. Circulating levels of lipid and gluconeogenic substrates were comparable in TS and control subjects and unchanged in response to treatment. Bone markers increased in response to GH. Total FM was increased in girls with TS, accounted for by an increased FM in the arms and trunk, whereas LBM was decreased. Especially LBM in the legs was decreased. Overall, bone mineral content was diminished. Treatment with GH reduced FM in TS, especially in the arms and legs, and likewise increased total LBM, primarily in the trunk.

Conclusion. This study documented evidence of impaired GH secretion and action, disproportionate body composition, but a normal carbohydrate metabolism in girls with TS. Short-term GH administration was associated with favorable changes in body composition but also with relative impairment of glucose tolerance and insulin sensitivity. We recommend that glucose metabolism be monitored carefully during long-term GH treatment in these patients.

Key Words: growth hormone treatment • glucose metabolism • insulin sensitivity • DXA scan • body composition • IGF-I • body mass index

Abbreviations: TS, Turner syndrome • GH, growth hormone • BMI, body mass index • OGTT, oral glucose tolerance test • IGF, insulin-like growth factor • IGFBP, insulin-like growth factor binding protein • FFA, free fatty acid • DXA, dual-energy x-ray absorptiometry • BMC, bone mineral content • LBM, lean body mass • FM, fat mass • HOMA, Homeostasis Model Assessment • ISI_comp, composite whole-body insulin sensitivity index • CV, coefficient of variation • RIA, radioimmunoassay • PTH, parathyroid hormone • FSH, follicle-stimulating hormone • LH, luteinizing hormone • AUC, area under the curve • BMD, bone mineral density

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Received for publication Oct 1, 2001; Accepted Apr 10, 2002.

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