| Objective:To explore the course of recombinant human growth hormone (rhGH) therapy in growth hormone deficiency (GHD) children reached the satisfactory final height and predicted factors,and to investigate the dynamic changes of FT4,TSH,ACTH,Cor and IGF-1 after hormone replacement therapy (HRT)Methods:314 patients with growth hormone deficiency (GHD) (228 boys and 86 girls) were enrolled.69.7% of the patients had isolated growth hormone deficiency (IGHD),30.3% multiple pituitary hormone deficiency (MPHD).36 of the patients, with mean age of (12.2+/-2.3) years, had reached the final height. Pretreatment chronologic age(CA), height SDS pre-and post-rhGH therapy, bone age (BA) and first year height velocity(HV), total therapeutic time and relationship among them were observed.50 growth hormone deficiency (GHD) children,whose clinical information were complete,were divided into Group IGHD and Group MPHD.These patients were followed up in 3 monthly interval.,to measure serum levels of free-thyroxine (FT4), thyroid stimulating hormone(TSH), adrenocorticotropic hormone(ACTH), cortisol(COR) and insulin-like growth factor-1 (IGF-1). And investigate the variance between two groups by application of Statistical Methods.Results:The first year HV was (13.7+/-2.8)cm/yr,height SDS increased from (-3.7+/-1.5) to the final height SDS (-0.3+/-0.6)SDS,and exceed the target height in patients whose BA under 7 years,and treatment course more than 48 months. The mean course of rhGH therapy needed (39+/-12)month,ranged (24-60)months; the course of rhGH therapy was positively correlated with pretreatment (CA-BA):rhGH therapy time(month)=14+6xpre-(CA-BA) (r=0.81, P<0.01).There was also a significant negative linear regression between the course of rhGH therapy and pretreatment HtSDS, giving a regression equation of rhGH therapy time(month)= 16-6.3xpre-HtSDS(r=-0.8, P<0.01).According to the data of 50 growth hormone deficiency (GHD) children,96.6% of multiple pituitary hormone deficiency (MPHD) patients displayed central hypothyroidism before therapy of rhGH,and 60% patient's levels of cortisol were under the normal range in group MPHD. L-T4 and hydrocortisol replacement therapy were start before rhGH therapy.The replacement therapy dosage of L-T4 was negatively correlated with pretreatment level of free-thyroxine (FT4):the dosage of L-T4 (μg·kg-1·d-1)=3.5-0.2×pre-FT4(pmol/L)(r=-0.80, F=81.44, P<0.01). There was also a significant negative linear regression between the replacement therapy dosage of hydrocortisol and pretreatment level of cortisol(COR), giving a regression equation of dosage of hydrocortisol (mg·m-2·d-1)=15.6-0.11×pre-COR (nmol/L)(r=-0.88, F=35, P<0.01).These phenomenas didn't occur in isolated growth hormone deficiency (IGHD) patient. The pretreatment levels of FT4 and Cor were positively correlated with the peak of growth hormone(GH), serum level of insulin-like growth factor-1 (IGF-1) and height of anterior pituitary and negatively with pretreatment (CA-BA). Serum level of insulin-like growth factor-1 (IGF-1) was significantly increased after HRT than that of pretreatment,and more obvious in MPHD than in IGHD.Conclusion:A long-term rhGH therapy are needed in GHD children to reach the final height,48 months or longer is the best,and the younger the better.The course of rhGH therapy can be predicted by(CA-BA)and pretreatment HtSDS.Central hypothyroidism and adrenal insufficiency with symptoms or no symptoms can be observed in majority of MPHD children,which may be exacerbated during the process of rhGH therapy.Complete hormone replacement therapy and regular monitoring are necessary to maintain FT4 in upper limit, and Cor in lower limit of normal range for the best growth effect of rhGH therapy. The pretreatment levels of FT4 and Cor were positively correlated with the peak of GH, serum level of IGF-1 and height of anterior pituitary, and negatively with pretreatment (CA-BA). Serum level of IGF-1 is a good index for GHD diagnosis and therapy monitoring.
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