Ellen M.N. Bannink

Puberty induction in Turner syndrome: results of oestrogen treatment on development of secondary sexual characteristics, uterine dimensions and serum hormone levels

Background  Besides short stature, gonadal dysgenesis leading to a lack of oestrogen is one of the main characteristics of Turner syndrome (TS). In most TS girls, puberty is induced with exogenous oestrogens.

Long-Term Follow-Up of GH-Treated Girls with Turner Syndrome: Metabolic Consequences

Aims: To investigate the metabolic consequences of long-term GH treatment in young women with Turner syndrome (TS), several years after GH discontinuation. Methods: Follow-up study of a randomized GH dose-response trial, with 3 GH dosages (1.3, 2.0, and 2.7 mg/m2/day). Thirty-nine TS patients (20.0 ± 2.1 years) participated 4.8 ± 1.9 years after GH discontinuation. Mean GH treatment duration was 8.7 ± 2.0 years. Fasting glucose, insulin, and serum lipids were measured. Results: Several years after GH discontinuation, insulin sensitivity remained lower, while β-cell function and fasting insulin levels remained higher than before treatment. Only BMI influenced β-cell function. Serum total cholesterol (TC), low-density lipoprotein and high-density lipoprotein (HDL) had further increased compared to 6 months after GH, resulting in higher TC, but also higher HDL levels compared to controls. The atherogenic index remained constant, but lower than controls. Conclusions: Besides height, GH therapy in girls with TS has additional beneficial effects on serum lipids. Nearly 5 years after discontinuation of GH therapy the favorable effect of GH was still noticeable. The GH-induced decrease in insulin sensitivity, however, remained unchanged, possibly due to having TS.

Long-Term follow-up of GH-treated girls with turner syndrome: BMI, blood pressure, body proportions

Aims: To investigate whether long-term growth hormone (GH) treatment influenced blood pressure (BP), body proportions and BMI in young Turner syndrome (TS) women several years after GH discontinuation. Methods: A follow-up study of a randomized GH dose-response trial with 3 GH dosages (1.3, 2.0, and 2.7 mg/m2/day). 39 TS patients (20.0 ± 2.1 years) participated 4.8 (1.9) years after GH discontinuation. Mean GH duration was 8.7 (2.0) years. Measurements: BP, BMI and body proportions. Results: During GH treatment, DBP had decreased. At the long-term follow-up study, DBP had increased and was similar to pretreatment levels. DBP was negatively influenced by GH dose. SBP was not influenced by GH dose or duration. The BMI increased gradually during and after GH therapy. During GH therapy, shape values of sitting height had decreased to normal values, of foot had increased, and both remained constant after GH discontinuation. Conclusions: GH therapy in girls with TS has, besides height, additional beneficial effects on BP and body proportions, except foot length. Nearly 5 years after ending GH, the favorable effect of GH on BP was still noticeable. The BMI increased gradually over the years, not influenced by GH.

Subclassification of Small for Gestational Age Children with Persistent Short Stature: Growth Patterns and Response to GH Treatment

Aim: We determined whether subclassification of short small for gestational age (SGA) children according to birth anthropometrics could delineate different patterns in gestation, delivery, postnatal growth, response to growth hormone (GH) treatment and parental height. Methods: 201 short SGA children were divided into three groups, SGAL, SGAL+W and SGAL+W+HC, according to birth length (L), weight (W) and head circumference (HC) ≤–2.00 standard deviation score (SDS). Results: SGAL+W+HC children were born after the shortest gestational age and more often by caesarean section than SGAL children (36.3 vs. 38.1 weeks, 68.4 vs. 24.4%). SGAL+W children had an intermediate pattern and experienced most gestational hypertension (p = 0.01). At birth, SGAL+W+HC children were shorter than SGAL or SGAL+W (–4.12 vs. –2.67 and –3.72 SDS, p ≤ 0.001). During the first 3 years of life, SGAL+W+HC children exhibited an increased growth in height (0.98 SDS) and HC (1.28 SDS) than SGAL (height, –0.06 SDS; HC, –0.30 SDS) and SGAL+W (height, 0.62 SDS; HC, –0.31 SDS). However, HC SDS remained smaller for SGAL+W+HC than the other groups at age 3. The groups did not differ in growth response during GH treatment. SGAL children tended to have shorter parents and target height than SGAL+W+HC children. Conclusions: Our study shows that subclassification of short SGA children might be a useful method for investigating SGA children as the subgroups revealed a different gestation, delivery and postnatal growth pattern. Response to GH treatment was not different between the groups.

Free dissociable insulin‐like growth factor I (IGF‐I), total IGF‐I and their binding proteins in girls with Turner syndrome during long‐term growth hormone treatment

Objective  To investigate the effect of GH treatment on free IGF‐I levels in girls with Turner syndrome (TS) and to verify relationships between free IGF‐I levels and total IGF‐I, IGFBP‐1, 2 and 3. Additionally, to analyse whether free IGF‐I, total IGF‐I, IGFBP‐3 or its ratio were related to IGF‐I bioactivity outcome parameters.

Adult height and health-related quality of life after growth hormone therapy in small for gestational age subjects

Objective: To estimate health-related quality of life (HRQoL) in non-growth hormone deficient (GHD) small for gestational age (SGA) children before and after growth hormone (GH) treatment to adult height (AH). Methods: This was a multicentre, two-arm trial. Following an initial 2-year double-blind study period, patients entered a 2-year extension period followed by treatment to AH. At baseline patients were randomised to GH (0.033 or 0.067 mg/kg/day) and continued treatment at that dose until AH. Height was assessed at baseline and 3-monthly intervals to AH (height velocity <2 cm/year). Height standard deviation score (SDS) before and after GH therapy was mapped onto estimated HRQoL scores up to AH. Results: Of the 79 children randomised into the study 53 were non-GHD (defined as peak GH >20 mU/L [peak 24-h GH value and peak arginine tolerance test]). At baseline these children had a mean (mean [±SD]) height SDS of −3.2 (0.7), height velocity SDS −0.6 (1.2) and age, 8.1 (1.9) years. Estimated HRQoL scores were significantly (p < 0.001) increased from baseline at AH (ΔHRQoL, 95% CI) (0.033 mg/kg/day, 0.112 [0.092, 0.132]; 0.067 mg/kg/day, 0.115 [0.094, 0.136]). HRQoL was not different between treatment groups. A significant gain in AH, relative to an SGA reference population, was reported in GH-treated patients. Mean (95% CI) ΔAH SDS (0.033 mg/kg/day, +1.4 [1.1, 1.6]. 0.067 mg/kg/day, +1.7[1.4, 2.0]). Limitations: The analysis assumes HRQoL can be mapped onto height SDS. Conclusions: GH treatment in short children born SGA without signs of persistent catch-up growth was associated with significant improvement in HRQoL and normalisation of AH.