Growth Hormone Injections: Uses and Side Effects
Children with Idiopathic Short Stature do not attain a normal adult height. The improvement of adult height with treatment with recombinant human growth hormone rhGH , at doses of 0.
The benefit obtained seems dose dependent and benefits of 7. The topic has remained controversial. The objective was to conduct a retrospective analysis of our experience with children with ISS treated with 0.
Eighty eight of our children 68 males and 20 females attained an adult height or near adult height of In the analysis of the subgroups, the adult height and adult height gain of children with non-familial short stature were significantly higher than of familial short stature. No difference was found in the cohorts with normal or delayed puberty in any of the subgroups, except between the non-familial short stature and familial short stature puberty cohorts.
This has implications for the interpretation of the benefit of treatment in studies where the number of children with familial short stature in the controls or treated subjects is not known. The treatment was safe. There were no significant adverse events. The IGF-1 values were essentially within the levels expected for the stages of puberty.
Our experience was quite positive with normalization of the heights and growth of the children during childhood and the attainment of normal adult heights, the main two aims of treatment.
Children with idiopathic short stature ISS do not attain a normal adult height. In the three randomized controlled studies Cochran Central Register Control Trials , the adult height of the controls was In an additional 6 non-randomized controlled studies the adult height of the controls ranged between Growth hormone treatment significantly improves the growth velocity and the adult height of children with ISS [ 10 - 13 ] and is considered safe [ 14 - 16 ]. Nevertheless, the use of growth hormone has remained controversial [ 17 - 19 ], mainly because of the modest benefit [ 20 , 21 ] and high cost [ 22 , 23 ].
Many of the studies, however, used GH doses of 0. Furthermore, some of the studies included children with intrauterine growth retardation or with familial short stature, which may have affected the results.
The benefit obtained seems dose dependent and mean benefits of 7. There have been also ethical issues raised [ 25 ] and considerations expressed as to whether ISS should be considered a disease, whether the degree of psychosocial morbidity warrants treatment [ 26 - 28 ], whether it is enhancement or endo-cosmetology rather than treatment [ 29 ], and whether treatment has any effect in health related quality of life [ 30 - 32 ].
As the name idiopathic indicates, the cause is unknown. A variety of genes affecting growth, of genes along the growth hormone IGF-I axis [ 33 - 38 ], polygenic traits determined by polymorphisms [ 39 ], heterozygous GHR mutations, a dominant negative mutation of the GHR causing familial short stature [ 40 ] and mutations in other genes have now been demonstrated in children previously classified as ISS [ 41 - 43 ].
So the label of normal short children may not be appropriate. All these concerns have been extensively discussed in a number of publications [ 44 ] and taken in consideration in the Consensus of the International Pediatric Endocrine Societies [ 45 ]. The interest of the child is the primary concern.
The main goal of the treatment is the normalization of the height during childhood and improvement of the adult height. Children with a height of less than -2 SDS [ 45 ] or a height of more than 2 SDS below their midparental target height, warrant consideration for treatment. Idiopathic short stature describes a heterogeneous group of children of unknown etiology with variable response to growth hormone [ 46 ].
It is defined as short children with a height below -2 SD 2. Ritalin [ 45 , 47 ]. Specifically, the children with ISS have normal birth weight, and no growth hormone deficiency [ 45 ].
The criteria do not include midparental height MPH. Thus, studies of idiopathic short stature have included two groups of children: Children with FSS, without treatment, may attain an adult height near or equal to midparental height, but shorter than the normal population [ 48 , 49 ].
It is possible, also, that the modest or small benefit obtained by growth hormone treatment in a number of studies was because many of the children were affected with familial short stature.
After the Consensus on the definition of idiopathic short stature in [ 50 ], ISS also includes what previously was known as constitutional delay of growth and puberty CDGP. A number of studies have indicated that the adult height attained in children with CDGP, with heights below -2 SDS, is less than the MPH and that they remain somewhat shorter than normal [ 51 , 52 ], some with average heights in the 10 th percentile [ 53 ] or 5 th percentile [ 54 , 55 ].
As the result of the aforementioned, there is consideration of the need to subcategorize the children into different groups: We conducted a retrospective analysis of our experience with children with ISS treated with rhGH, with the aim of comparing the different subgroups and assessing the benefit by comparison with historical controls. The study was approved by the Institutional Review Board of the Hospital and consent and assent approvals were obtained. Of the children with idiopathic short stature treated with rhGH 0.
The groups were further divided into those with normal puberty and delayed puberty. The duration of treatment was 5. All the children met the criteria for ISS with the height below The age at start of treatment ranged between 4. With the normal weight gain the dose would decrease to 0. The dose ranged from 0. The dose was not increased for puberty.
An MRI of the brain was obtained at the time of the growth hormone stimulation testing on many of them in the past. This is no longer felt needed. Karyotypes were obtained in many. Bone age was determined by Greulich and Pyle standards and adult height predicted by Bayley-Pinneau tables.
Heights were measured by a wall-mounted stadiometer. The heights at the onset of treatment were expressed as SDS for chronologic age. The height SDS was calculated in the usual manner: The last bone age available in our records was To obtain final adult heights, the potential remaining growth of some children whose heights were obtained before closure of the epiphyses near adult height was calculated.
These numbers for calculated final adult heights were not included in the numbers reported and it will be addressed later Additional file 1: Pubertal development was assessed by the method of Tanner. Males with testicular volume of less than 4. Children whose heights were below the midparental height SDS target range of Children whose fathers or mothers were below The classification of delayed onset of puberty includes the previously used definition of constitutional delay of growth and puberty CDGP in accordance with the international consensus [ 45 ].
Target height MPH was calculated from the self-reported parental heights by the method of Tanner: No addition for secular trend was needed, since there was no or minimal increase in secular trend in the United States National Health Statistics between and Midparental height SDS was calculated by the following equation: All had a good response to rhGH treatment.
An analysis of intent to treat to adult height was conducted. Growth hormone secretion was evaluated by hours overnight frequent sampling on a number of the children in the s; we no longer do that. This method was not available early in the study and a number of the determinations were made as Somadomedin C.
Paired and unpaired, two-tailed Student T test was used to compare the means of the different groups. A p value of 0. Correlations to assess the factors influencing AHs young age, delayed bone age, distance to MPH, etc.
Growth charts of 3 individual males showing the response to GH treatment. Height SDSs of all subjects, males and females, before and after treatment. All ISS males and females, B. All ISS males, and C. All of them attained a height within 2 SD except two children with familial short stature, The average height of the 88 children was The adult height gain was 1. The 20 females attained an adult height of The adult height gain was 2.
The only difference between the males and the females was in the MPH of The mean adult height of Also for the females the mean adult height of The mean adult height attained by the 47 males was The latter statistically different, but it would appear to be of no clinical significance 2. The adult height of the 20 children with normal puberty, In the 27 children with delayed puberty the adult height of In the 16 female children with NFSS, the adult height was The adult height gain for the 47 males with NFSS was 2.
The adult height attained by the 21 males was The number of females with FSS was only 4 and the values may not accurately represent the values of a larger group.
The adult height was The adult height of The adult height gain for the 47 NFSS was 2. There was no difference in the baseline heights,