Growth hormone treatment for Turner syndrome in Australia reveals that younger age and increased dose interact to improve response

P>Objective To investigate response to growth hormone (GH) in the first, second and third years of treatment in the total clinical cohort of Turner syndrome (TS) patients in Australia. Context Short stature is the most common clinical manifestation of TS. GH treatment improves growth. Design Response was measured for each year of treatment. Stepwise multiple regression analyses were used to identify factors that significantly influenced response. Patients Prepubertal TS patients who completed 1 year (n = 176), 2 year (n = 148), or 3 year (n = 117) of treatment and were currently receiving GH. Measurements Change in TS specific Height Standard Deviation Score (Delta TSZ) was the main response variable used. Major influencing variables considered included dose, starting age and height, BMI, bone age delay, karyotype, parental height, and interactions between dose and starting age or height. Results Response was greatest in first year and declined thereafter (median Delta TSZ: 1st year = +0 center dot 705, 2nd year = +0 center dot 439, 3rd year = +0 center dot 377) despite the median dose increasing [1st year = 5 center dot 5 mg/m2/week (0 center dot 23 mg/kg/week), 2nd year = 6 center dot 4(0 center dot 24), 3rd year = 7 center dot 2(0 center dot 26)]. An Age*Dose interaction was identified influencing first, second year, and total Delta TSZ. The Delta TSZ over 3 years was significantly influenced by first-year dose. Dose increments only attenuated the general decline in response. An acceptable first-year response (delta TSZ > 1 center dot 01) was achieved by only 17 center dot 6% of patients. Conclusions Growth response is greatest and most influenced by dose in the first year. Dose in first year is a major factor contributing to total response. A starting Age*Dose interaction effect was observed such that young girls on a high dose respond disproportionately better. Optimal GH treatment of short stature in TS thus requires early initiation with the highest safe dose in the first year