Growth and Growth-Promoting Therapy in Turner Syndrome

Abstract

The diagnosis of Turner syndrome (TS) requires the presence of characteristic physical features in phenotypic females coupled with complete or partial absence of the second sex chromosome, with or without cell line mosaicism. Most girls with Turner syndrome (TS) are short in childhood as well as in adulthood. Short stature is mainly caused by haploinsufficiency of the short-stature homeobox-containing gene (SHOX) located on the X chromosome, but the precise mechanism is still unknown. Although girls with TS are not growth hormone (GH) deficient, treatment with biosynthetic recombinant human GH accelerates height velocity and increases adult height. A younger starting age, taller parents, a higher GH dose, daily GH injections, good compliance, good short-term effect, and the addition of low dose (0.03 mg/kg per day) of oxandrolone are associated with a higher gain in adult height during GH treatment. In most girls with TS, ovarian failure results in an absence of puberty. If growth-promoting therapy has been optimized, it is desirable and possible to start with low-dose estrogens at a pubertal age to induce puberty. Long-term GH treatment, even using a 1.5–2 times higher dose than the standard GH dose for TS, seems to be safe: no negative effect on heart contractility and ventricular function, aorta diameter and distensibility, blood pressure, glucose levels, blood lipids, and bone mineral density has been found. During GH treatment, a disproportionately greater increase of foot size than height is found in girls with TS, which has to be considered mainly a part of the natural development in TS, albeit influenced by higher GH dosages. Continued observation into adulthood is, however, required to assess possible long-term side effects of the increased insulin and IGF-I levels during GH treatment. Concerning the addition of Ox to GH, especially the higher (0.06 mg/kg per day) Ox dose results in abnormal voice deepening and other forms of virilization in a part of the girls. Growth promotion in TS aims to improve well-being and quality of life and decrease practical and psychosocial problems related to short stature. However, conclusive evidence for a beneficial effect of GH treatment on well-being in patients with TS is lacking. Consequently, clinicians should not only focus on height improvement but also consider other health-related problems (including infertility) in Turner patients.