The Results of the patients treated with recombinant growth hormone between 1990 and 2002 in Dokuz Eylül University, Deparment of Pediatric Endocrinology and Metabolism and factors affecting response to growth hormone therapy

the Results of The Patients Treated with Recombinant Growth Hormone Between 1990 and 2002 in Dokuz Eylül University, Department of Pediatric Endocrinology and Metabolism and Factors Affecting Response to Growth Hormone Theraphy Aim: Retrospective analysis of the patients treated with recombinant Growth Hormone (rGH) between 1990 and 2002 in Dokuz Eylül University, Department of Pediatric Endocrinology and Metabolism to evaluate results of rGH therapy, and to investigate factors affecting response to rGH and side effects of rGH treatment. Subjects and Methods: Seventy-seven children who treated with rGH at least 1 year throughout 12 years have been studied. Birth histories, heights of mothers and fathers, auxological data before and after treatment, pubertal status and ages at the start of therapy, duration of therapy and height velocities (HV) during the first 3 years of the patients have been recorded. Height SDS, Weight for height (W/H), target height (TAH) SDS have been calculated with standard growth charts and initial height SDS-height SDS after treatment has been recorded for each patient. Bone ages (BA) were determined according to G&P and predicted adult height (PAH) was calculated according to Bayley-Pinneau method. Results: Forty (52%) of total 77 patients were boy and the remaining 37 (48%) patients were girl. 59 (76.6%) children had isolated GH deficiency (IGHD), 8 (10.4%) children had multiple pituitary hormone deficiency (MPHD), 7 (9.1%) girls were diagnosed as Turner syndrome and the remaining 3 (3,9%) children treated with rGH because of intrauterine growth retardation, chronic renal failure and XY gonadal dysgenesis. The mean age at the start of treatment was 11,2 ± 2,9 year, median rGH treatment period was 3,8 ± 2,6 year and mean TAH was -0,8 ± 0,94. At the end of rGH therapy; Aheight SDS and APAH SDS were 1,02 + 1 and 0,52 ± 0,99, respectively. There was a significant difference between before and after treatment's height SDS (-3,09 ± 0,88 and - 2,05 ± 1, p < 0,05) and PAH SDS (- 1,6 ± 1,17 and -1,17 ± 1,16, p < 0,05). HVs before therapy and during 1st, 2nd and 3rd year of therapy were 3,27 ± 1,6, 7,8 ± 2,06, 6,2 ±2,1 and 5,3 ± 2,22 cm, respectively. HV during 1st year was found significantly higher than 3rd year (p < 0.05). After exclusion of patients with MPHD and gonadal dysgenesis, the remaining 61 patients divided into 2 groups based on pubertal status at the start of rGH therapy; 40 (65%) pre pubertal and 21 (35%) pubertal. The mean age of 2 groups at the start of treatment was 10,1 ± 2,7 and 13,5 ± 1,6, p < 0.05, and median rGH treatment period was 3,8 ± 2,6 and 2,3 ± 0,87, p < 0.05, respectively. A significant difference was found between 2 groups for CA/BA before treatment (1,4 + 0,38 and1,1 ± 0,12, p < 0,05). After treatment, PAH SDS (- 0,96 ± 0,98 and - 1,49 ± 0,8, p < 0,05), APAH SDS (0,24 ± 0,83 and -0,15 ± 0,90, p < 0,05) and HV during 3rd year (5,6 ± 1,6 cm and 3,9 ± 2,4 cm, p < 0,05) were significantly higher in pre-pubertal group than pubertal group. Before treatment, the mean height SDS in patients with IGHD, MPHD and Turner Syndrome were (-2,8 ± 0,76, -4,03 ± 1,07 and -3,4 ± 0,67, respectively; p < 0,05) and PAH SDS were (- 1.4 ± 1,11, -2,2 ± 1,5 ve -2,4 ± 0,97, p < 0,05). CA/BA was significantly higher in MPHD group than IGHD and Turner group (1,3 ± 0,34, 2 ± 0,97 and 1,2 ± 0,18, p < 0,05). The median duration of rGH therapy was found significantly higher in MPHD group compared with the others ( 3,35± 2,3, 7,9 ± 3 and 3,25 ±1,6 year, p < 0,05). After treatment; more pronounced high values in Aheight SDS was found in MPHD group (0,92 ± 0,64, 2,04 ± 1 and 1,04 ± 1,4, p < 0,05). HV was significantly higher in MPHD during 1st year (8,04 ± 1,76, 9,3 ± 1,8 and 5,8 ± 2.05 cm, p < 0,05) and significantly low in Turner group during 2nd and 3rd year of therapy ( 2nd yean 6,4 ± 2,05, 7,3 ± 1,8 and 4,6 ± 1,5 cm p < 0,05, and 3rd year: 5,4 ± 1,79 6,3 ± 3,3 and 3,9 ± 1,4 cm, p >0,05). Twenty-six patients (17 with IGHD, 7 with MPHD and 2 with Turner syndrome) reached final height with rGH therapy.Final height SDS were found -1,8 ± 0,75, -2 ± 1,4 and -0,86 ± 0,72 in 3X groups respectively. Before treatment, Height SDS (-2,96 ±0,78 and -4,02 ±1,16, p < 0,05) and HV (4,6 ±1,1 and 1,33 ± 0,75 cm, p < 0,05) were found significantly higher in IBHD group. The median duration of therapy (3,4 ± 2,4 and 7,4 ± 2,9 year, p < 0,05), and Aheight SDS after treatment (1,11 ± 0,71 and 2,02 + 1,14, p < 0,05) were significantly low in patients with IGHD than MPHD group. There was a positive correlation between duration of therapy and Aheight SDS ( r= 0,34, p < 0,05). A negative correlation was found between age at the start of therapy and CA/BA before treatment and HV during 3rd year (r= -0,31, p < 0,05; r= -0,37, p < 0,05). Height SDS before therapy was found to be positively correlated with PAH SDS before treatment, height SDS after treatment, Aheight SDS and HV during 3rd year (r= 0,65, p < 0,05; r= 0,57, p < 0,05; r= 0,54, p < 0,05; r= 0,35, p < 0,05; r= 0,38, p < 0,05). PAH before treatment was found to be positively correlated with height SDS and PAH SDS after treatment, HV during 3rd year and negatively correlated APAH SDS (r= 0,46, p < 0,05; r= 0,64, p < 0,05; r= 0,44, p < 0,05 ; r=- 0,56, p < 0,05). There was a positive correlation between Height SDS after rGH therapy and HVs during 1st, 2nd and 3rd year(r= 0,48, p < 0,05; r= 0,25, p < 0,05; r=- 0,56, p < 0,05; r= 0,47, p < 0,05). CA/BA before treatment was positively correlated with Aheight SDS and HVs during 2nd and 3rd year (r= 0,30, p < 0,05. r= 0,25, p < 0,05 r= 0,37, p < 0,05). Neither pik GH levels which were obtained after GH stimulation testing nor TAH SDS were to be correlated with response to rGH. No side effect such as pseudotumor cerebri, slipped capital epiphysis, fluid retention, hyperglycemia or neoplasm was determined during study period. Conclusion: This study showed that increases in HV after rGH treatment are more pronounced during 1st year of treatment and then reduce gradually. Response to rGH treatment is better in MPHD than IGHD and Turner syndrome. Patients with Turner syndrome show similar growth rates during 1st year of treatment compared with IGHD and MPHD. Height SDS before treatment, duration of rGH therapy, age, pubertal status and CA/BA at the start of treatment seems to be important predictors of response to rGH therapy. Ttreatment with rGH can be considered a safe intervention for children with various growth disorders.