SGA and Turner Syndrome: the impact of growth hormone treatment on physical and mental well-being

textabstractBy definition, 2.3% of the children is born Small for Gestational Age (SGA), which is a length and/or height < -2 standard deviation (SD). Most children born SGA show catch-up growth during the first years of life. Approximately 10% of them remain short with a height below the normal range. Previously, this study showed that long- term growth hormone (GH) treatment in short SGA children resulted in an adult height within the normal range in 85%, and in 98% a height within the target height range (i.e. the midparental height). The mean gain in height is 11-13 cm in girls and 12-14 cm in boys. In Turner syndrome (TS), one of the main characteristics is short stature. The mean adult height of women with TS is approximately 20 cm below normal, which is about 148 cm in the Netherlands. GH treatment in girls with TS resulted in an adult height within the normal range in 83%, and in 63% a height within the target height range. The mean height gain is between 12 and 17 cm. Another major characteristic of TS is gonadal dysgenesis, leading to ovarian failure in 80-100% of the Turner patients. Most girls do not enter puberty spontaneously due to a lack of estrogen production. Therefore, puberty is induced by administration of exogenous estrogens. Route, timing, dose, and form of estrogen therapy are still issues of debate. These studies investigated different aspects of long-term GH treatment in children born SGA (n = 72) and girls with TS (n = 65). The effects of long-term GH treatment on the IGF-system, especially the free fraction of IGF-I (chapter 2 and 3), and the quality of life after ending GH treatment (chapter 4 and 5) are discussed. In TS girls we described the pubertal development and uterine dimensions, after puberty has been induced starting with a low estrogen dose during GH treatment, at an appropriate age (Chapter 6). Several years after the end of GH treatment, we measured serum lipids, insulin and glucose metabolism, body mass index (BMI) and body proportions in 39 TS girls (chapter 7). At the same time, we also investigated aortic dimensions and aortic distensibilities, representing aorta wall function (chapter 8). Chapter 1 provides a general overview of the literature regarding SGA and TS. In this chapter definitions, etiology, prevalence and clinical characteristics of these two patient populations are described. In addition, it gives a summary of the previously reported results of the GH treatment regarding the growth effects, safety aspects, and other possible GH effects. In the girls with TS, the puberty induction is discussed. At the end of this chapter, a time-frame is given of these two long-term GH studies (SGA study started in 1991 and the TS study started in 1989), and an overview of the different doctoral dissertations resulting from these studies. Finally, the objectives of the different studies presented in this dissertation are described