Growth hormone treatment in Turner's syndrome: short and long-term effects on metabolic parameters

The effect of GH administration on various metabolic parameters and on growth and bone age development was studied in patients with Turner's syndrome.

Patients were treated with daily s.c. GH (20 IU/m2/week) and ethinyloestradiol p.o. (100 ng/kg/day) during the first year and with additional oxandrolone (0.125 mg/kg/day) during the second year. The responses of free fatty acids (FFA), urinary excretion of hydroxyproline (HP) and IGF-I were evaluated after short-term GH application. Glucose tolerance was investigated before any therapy, during treatment with GH and oestradiol and after adding oxandrolone, respectively. The course of growth, bone age and IGF-I levels was followed throughout the study.

Eleven patients with Turner's syndrome aged 12.6 +/- 1.9 years (mean +/- SD) were included.

Free fatty acids increased significantly 4 hours after one s.c. injection of GH (0.7 +/- 0.2-1.1 +/- 0.3 mmol/l; mean +/- SD). Mean urinary hydroxyproline excretion remained unchanged after 6 weeks of GH therapy (337 +/- 206-299 +/- 145 mumol/m2/24 h), but there was a significant negative correlation between individual hydroxyproline values and the peak serum GH followed stimulation. IGF-I was in the prepubertal range and increased significantly after 3 days of GH injection (30.0 +/- 10.0-42.5 +/- 10.0 nmol/l). Growth velocity (in Turner's syndrome related SD) increased from 0.0 +/- 0.3 SD before treatment to 0.9 +/- 0.8 SD after the first year and to 3.4 +/- 1.3 SD during the second year of treatment. There was no undue acceleration of bone age. During long-term treatment, IGF-I increased significantly only when oxandrolone was added. Two patients had impaired glucose tolerance prior to GH therapy and three additional children developed impaired or abnormal glucose tolerance after GH therapy. Insulin concentrations increased significantly only after introduction of oxandrolone.

Patients with Turner's syndrome who had lower basal IGF-I levels had significantly higher responses of IGF-I, free fatty acids and hydroxyproline (P less than 0.01 for all parameters) after short-term GH application. The data indicate adequate endocrine and metabolic responses in patients with Turner's syndrome which are the basis for growth promoting action. A considerable number of patients had impaired glucose tolerance during GH treatment.