ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab. 2020 Aug 1;105(8):dgaa274.

This retrospective study evaluated the long-term effects of GH treatment (median duration 6.7 years) in 63 girls with Turner syndrome (TS) whose GH doses were titrated to maintain IGF-I levels within the normal range. The median GH dose to maintain normal IGF-I levels was 33 (g/kg/day. Across all TS karyotypes, IGF-I titrated GH dosing led to a median adult height (AH) of 1.25 SDS by age-specific TS references, and a median gain in height (adult height minus baseline height SDS) of 0.50 SDS, corresponding to only 3.2 cm.

TS is characterized by X deficiency due to a complete or partial loss of one X chromosome (1). The clinical spectrum is wide, including short stature, ovarian dysgenesis with hypergonadotropic hypogonadism, cardiac malformations, metabolic disorders, osteoporosis and autoimmune disorders. A variable combination of prenatal growth failure, impaired childhood growth and the lack of a pubertal growth spurt leads to short adult height, approximately 20 cm shorter than the normal population. TS is a recognized indication for GH therapy which increases adult height by on average 7.22 cm in comparison with untreated TS girls (2)(3).

As short stature in TS females is due to haploinsufficiency of the short stature homeobox-containing (SHOX) gene, instead of anomalies in GH/IGF-I axis, GH administration often results in higher than normal circulating IGF-I levels. It is generally accepted that IGF-I levels should be monitored during GH treatment and maintained within the normal range for age and sex (4). According to the current study, the GH dose needed to maintain IGF-I within the normal range (33 (g/kg per day) is lower than that currently recommended for TS (45–50 μg/kg per day) (4) and the use of IGF-I titration for tuning GH dose reduces the overall height gain. This study emphasizes the difficulty of balancing the optimal height growth response with normal IGF-I levels for achieving the best clinical outcome for girls with TS without jeopardizing their safety.

References:

1. Gravholt CH, Viuff MH, Brun S, Stochholm K, Andersen NH. Turner syndrome: mechanisms and management. Nat Rev Endocrinol. 2019;15(10):601–14.

2. Bondy CA. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92(1):10–25.

3. Li P, Cheng F, Xiu L. Height outcome of the recombinant human growth hormone treatment in Turner syndrome: a meta-analysis. Endocr Connect. 2018;7(4):573–83.

4. Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol. 2017;177(3):G1–g70.