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Body Proportions during Long-Term Growth Hormone Treatment in Girls with Turner Syndrome Participating in a Randomized Dose-Response Trial¹

Department of Pediatrics, Division of Endocrinology (Th.C.J.S., S.M.P.F.M.K.-S., A.T., S.L.S.D.) Sophia Children’s Hospital, 3015 GJ Rotterdam, The Netherlands; Academic Hospital Maastricht (W.J.G., R.B.) and the Department of Epidemiology and Biostatistics, Erasmus University (T.S.), Rotterdam, The Netherlands; and the Department of Epidemiology and Public Health, Institute of Child Health (T.J.C.), London, United Kingdom

Address all correspondence and requests for reprints to: Theo C. J. Sas, M.D., Division of Endocrinology, Sophia Children’s Hospital, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.

To assess body proportions in girls with Turner syndrome (TS) during long term GH treatment, height, sitting height (SH), hand (Hand) and foot (Foot) lengths, and biacromial (Biac) and biiliacal (Biil) diameters were measured in 68 girls with TS participating in a GH dose-response trial. These previously untreated girls with TS, aged 2–11 yr, were randomly assigned to 1 of 3 GH dosage groups: group A, 4 IU/m²·day; group B, first year 4 and thereafter 6 IU/m²·day; group C, first year 4, second year 6, and thereafter 8 IU/m²·day. Seven-year data were evaluated to assess the effect of GH treatment on body proportions during childhood. In addition, data from all girls who had reached adult height were evaluated to determine the effect on the adult body proportions. All results were adjusted for age and sex and expressed as SD scores using reference values of healthy Dutch girls. To describe the proportions of SH, Hand, Foot, Biac, and Biil to height, these values were adjusted for the SD score of height and were expressed as shape values, using the formula, e.g. for SH: shape SH = (SH SD score - height SD score)/(2 - 2 x correlation coefficient between SH and height in the reference population). Furthermore, SD scores using references of untreated girls with TS were calculated for height and SH. Values less than -2 or more than +2 were considered outside the normal range.

At baseline, the shape values of all measurements were significantly higher than zero, but most mean shape values were still within the normal range. Seven-year data of 64 girls and adult height data of 32 girls showed that an increase in height was accompanied by an even higher increase in Foot, resulting in mean SD scores above zero and shape values of +2 and higher. The increase in the shape value of Foot was significantly higher in groups B and C compared to that in group A after 7 yr of GH treatment, but there were no significant differences between the GH dosage groups in the girls who had reached adult height. The shape values of SH had decreased to values closer to zero after reaching adult height, especially in group A. A similar pattern in the relationship of SH to height was seen using references of girls with TS. No significant changes in the other proportions were found after reaching adult height.

In conclusion, on the average, untreated girls with TS have relatively large trunk, hands, and feet, and broad shoulders and pelvis compared to height. The increase in height after long term GH treatment is accompanied by an even higher increase in Foot and a moderate improvement of the disproportion between height and SH. Recently published reference data from untreated adults with TS and the results of a different patient group receiving a comparable GH dosage suggest that the disproportionate growth of feet has to be considered a part of the natural development in TS, but might be influenced by higher GH dosages. The development of large feet can play a role in the decision of the girl to discontinue GH treatment in the last phase of growth.