Pituitary somatotropic function in girls with the Shereshevsky-Turner syndrome

In order to assess how lack of estrogens may influence the regulation of growth hormone (GH) secretion, we studied GH response to intravenous GHRH(1-29)NH2 in a dose of 1 mg/kg and standard oral clonidine and L-DOPA stimulation in 25 girls with Turner's syndrome (TS) aged 4 to 14. None of the patients had signs of spontaneous puberty or were administered any growth-promoting treatment before testing. Since gonadotrophin elevation is commonly observed in girls with TS at the age of 9 years, the patients were divided into 2 groups: those aged 4 to 9 (n=9, group A) and 9 to 14 (n=16, group B). Maximum GH level following clonidine stimulation was appreciably decreased in older girls (p<0.01). GHD (max level after standard provocation test no more than 7 ng/ml) was confirmed only in group В (67%). The peak GH responses to L-DOPA and GHRH did not vary much within groups A and В (mean ± SEM 12.9 ± 4.7 versus 8.5 ± 2.3 and 34.2 ± 8.0 versus 33.0 ± 9.7 ng/ml, respectively). In both groups, the weighed average for GH levels (AUC divided by time) after GHRH stimulation was higher than after L-DOPA, although the difference was less significant in group A (18.8 ± 2.6 versus 6.4 ± 2.6 ng/ml, p=0.17) than in group В (13.1 ± 5.1 versus 2.5 ± 0.6 ng/ml, p<0.05). To evaluate the effect of estrogen therapy on the GH axis, all girls in group В were tested again after 6 months of oral dihydrostilbestrol in a daily dose of 1.0 mg. Estrogen therapy resulted in an appreciable boosting of GH response to L-DOPA (GH AUC over 120 min, 1425.2 ± 444.6 versus 316.4 ± 77.3 ng/ml • min, p=0.03), but did not influence the response to GHRH (GH AUC over 90 min, 1219.8 ± 259.9 versus 1375.7 ± 636.6 ng/ml • min, p=0.5). Our results indicate that somatotroph response to exogenous GHRH stimulation in TS is not age-dependent. Replacement of estrogen did not influence GH secretion induced by GHRH but appreciably improved the response of GH to L-DOPA in older patients. Hence, we may conclude that pubertal-aged girls with TS may develop hypothalamic GH insufficiency of a certain degree due to primary ovarian failure.

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